Qhov Sib Txawv Ntawm Kev Cuam Tshuam Hauv Kev Noj Qab Haus Huv Thaum Ntxov Thaum Ntxov Mis nyuj muaj qhov sib txawv ntawm cov leukocyte thoob ntiaj teb kev hloov pauv cov ntaub ntawv, Kev Noj Qab Haus Huv thiab Fertility Raws li Parity

Abstract:Kev ua haujlwm ntawm circulating leukocytes nyob rau hauv nyuj nyuj yog suppressed tom qab calving, nrog tsis zoo zog tshuav nyiaj li cas raws li ib tug muaj feem yuav. Leukocyte transcriptomic profiles tau muab piv rau nyias nyob rau hauv 44 multiparous (MP) thiab 18 primiparous (PP) Holstein-Friesian nyuj tau txais kev noj zaub mov txawv hauv kev sib piv los ntsuas seb puas muaj lub cev tsis muaj zog tuaj yeem txo tau los ntawm cov khoom noj tsim nyog. Tom qab calving, nyuj tau muab ob qho tib si (1) qis concentration (LC); (2) nruab nrab concentrate (MC), los yog (3) siab concentrate (HC) noj nrog proportions ntawm concentrate rau nyom silage ntawm 30%: 70%, 50%: 50%, thiab 70%: 30%, feem. Cov ntaub ntawv nyuj phenotype tau sau suav nrog cov kab mob metabolites, cov kua mis tawm los, thiab cov ntaub ntawv kev noj qab haus huv thiab fertility. RNA sequencing ntawm circulating leukocytes ntawm 14 hnub nyob rau hauv cov mis nyuj yog ua. Kev noj haus HC tau txhim kho lub zog sib npaug hauv ob pawg hnub nyoog. Muaj ntau qhov sib txawv ntawm cov noob hauv PP dua li hauv MP nyuj (460 vs. 173, HC vs. LC piv) nrog ob peb sib tshooj. MP nyuj nyob rau hauv LC noj zaub mov tau qhia upregulation ntawm lub complement thiab coagulation cascade thiab innate lub cev tiv thaiv mechanisms tiv thaiv kab mob thiab muaj ib tug sib txawv ntawm ntau kis ntawm mastitis thiab pluag fertility. Hauv qhov sib piv, PP nyuj ntawm HC noj zaub mov tau pom ntau dua lub cev tiv thaiv kab mob raws li ob qho tib si gene qhia thiab phenotypic cov ntaub ntawv thiab ncua sij hawm ntev ntawm calving rau conception. Cov leukocytes ntawm MP thiab PP nyuj yog li teb qhov sib txawv ntawm cov zaub mov ntawm lub hnub nyoog, kev noj zaub mov zoo, thiab kev tiv thaiv kab mob cuam tshuam rau lawv txoj kev noj qab haus huv thiab kev xeeb tub tom qab.

Desert ginseng-Improve immunity (21)

cistanche cov txiaj ntsig rau txiv neej-ua kom muaj zog tiv thaiv kab mob

Nyem qhov no mus saib Cistanche Enhance Immunity khoom

【Nug ntxiv】 Email: cindy.xue@wecistanche.com / Whats App: 0086 18599088692 / Wechat: 18599088692

Ntsiab lus:postpartum kev tiv thaiv kab mob; innate kev tiv thaiv; metabolism; leukocytes; lactation noj cov zaub mov; Cov ntawv sau tseg; kev yug me nyuam; nyuj

1. Taw qhia

Thaum ntxov tom qab yug me nyuam, nyuj cov mis nyuj yog tus cwj pwm los ntawm kev tiv thaiv kab mob uas cuam tshuam rau hauv lub cev thiab kev tiv thaiv kab mob, nrog rau kev tiv thaiv kab mob ntawm tes thiab kev lom zem. Circulating leukocytes yog recruited rau hauv cov ntaub so ntswg xws li lub caj pas mammary thiab endometrium thaum o. Cov kev tshawb fawb yav dhau los tau, txawm li cas los xij, tau pom qhov txo qis ntawm cov lej leukocyte thiab lawv lub peev xwm ua haujlwm thaum lub sijhawm peripartum [1,2]. Kev tshaj tawm cov teebmeem suav nrog kev ua tsis taus phagocytosis thiab oxidative tawg ua haujlwm [3-5], txo qis kev ua haujlwm ntawm T-cells mus rau cov neeg ua haujlwm mitogenic, thiab txo qis ntawm immunoglobulin los ntawm B-cells [6,7]. Cov laj thawj yog multifactorial tab sis tshwm sim txuas rau kev faib khoom noj hauv kev pom zoo ntawm cov kua mis thaum pib lactation, cuam tshuam kev tiv thaiv kab mob [8-10]. Leukocytes yuav tsum muaj cov piam thaj kom txaus, ntau yam fatty acids, thiab cov roj (cholesterol) lossis oxysterols rau lawv cov kev saib xyuas thiab kev ua haujlwm [8,11,12]. Txawm li cas los xij, qhov muaj cov khoom noj muaj txiaj ntsig yog qhov tseem ceeb rau lub caj pas mammary tom qab calving, xav tau kwv yees li 25% ntau metabolizable zog thiab protein ntau dua li muab los ntawm kev noj zaub mov [8,13,14]. Tsis tas li ntawd, kev pub niam mis yog tus cwj pwm los ntawm cov txheej txheem inflammatory uas cuam tshuam nrog kev hloov pauv hauv kev tso tawm ntawm ntau yam prostaglandins, steroids, thiab cytokines thiab raug mob thaum lub sij hawm tus me nyuam nws tus kheej [15-17]. Cov inflammatory teb rau calving thiab metabolites tso tawm thaum lub sij hawm cov ntaub so ntswg mobilization muaj zog anorexic teebmeem, ntxiv txo kom tsawg thiab exacerbating qhov tsis zoo zog tshuav nyiaj li cas (NEB) [18]. Thaum noj zaub mov tsis tuaj yeem ua tau raws li qhov xav tau ntawm lub zog, nyuj nkag mus rau lub sijhawm NEB, nrog rau qee tus neeg ua metabolically imbalanced [19–21]. NEB yog txuam nrog insulin tsis kam, txo qis hepatic growth hormone (GH) receptor qhia, thiab qis hepatic IGF-1 synthesis [22,23]. Kev tsis sib txuas ntawm GH nrog cov tshuaj insulin hauv cov nyuj tom qab yug menyuam yog qhov kev hloov pauv uas tseem ceeb ntawm cov piam thaj hauv cov ntaub so ntswg xws li mammary epithelial cells, hauv qhov kev noj qab haus huv yog ywj pheej ntawm insulin [8]. Hauv qhov xwm txheej no, kev sib tw rau lub zog muab khoom nruab nrab ntawm lub caj pas mammary thiab lub cev tiv thaiv kab mob yog yam tsis muaj kev zam vim tias lawv ob leeg tso siab rau tib qho tseem ceeb substrates thiab ob qho tib si yog cov neeg siv khoom loj ntawm lub zog. Kvidera et al. [24] pom tau tias kev ua kom lub cev tiv thaiv kab mob tag nrho hauv nyuj yuav tsum tau 2.5 mus rau 3.1 Kg qabzib ib hnub. Qhov no zoo ib yam li qhov xav tau ntawm 2.7 kg / d ntawm cov piam thaj los ntawm mammary epithelial hlwb rau cov kua mis ntawm 40 kg / d [8].

Kev sib koom ua ke ntawm cov ntaub so ntswg kuj tseem cuam tshuam nrog kev nce ntxiv ntawm cov roj ntsha uas tsis yog-esterified fatty acids (NEFAs), beta-hydroxybutyrate (BHB), thiab txo IGF-1, tag nrho cov uas ua rau lub cev tsis muaj zog [5,9,10,20 ]. Piv txwv li, peb txoj kev tshawb fawb tsis ntev los no tau qhia tias leukocyte cell-to-cell adhesion tau inhibited thaum NEFA concentration siab tshaj 750 µM [25]. Txawm hais tias kev siv cov ntaub so ntswg yog ib qho kev hloov pauv ntawm cov tsiaj nyeg los txhawb kev lactation, ntau cov kev tshawb fawb tau pom tias NEB hnyav muaj qhov cuam tshuam loj rau tus nyuj tom qab muaj peev xwm xeeb tub hauv lub sijhawm [26]. Qhov no tuaj yeem yog vim muaj ntau yam xws li ncua sijhawm ntawm kev kho kom zoo ntawm lub tsev menyuam ib puag ncig [2]; ncua sij hawm ntawm anovulation [27], ib puag ncig tsis zoo intrafollicular [28], thiab tsis zoo oocyte tsis zoo [29]. Mis nyuj heifers feem ntau calve nyob ib ncig ntawm 90% ntawm lawv lub cev qhov hnyav [30]. Peb txoj kev tshawb fawb yav dhau los tau pom tias cov nyuj primiparous (PP) muaj cov tshuaj insulin ntau dua, IGF-1, thiab leptin concentrations hauv lawv txoj kev ncig, qis dua cov ntshav metabolites (BHB, NEFAs, thiab urea), thiab cov piam thaj ntau dua li multiparous (MP). ) nyuj tsawg kawg yog 7 lub lis piam tom qab calving [31,32]. Qhov no qhia tau hais tias muaj tsawg dua uncoupling ntawm somatotrophic axis nyob rau hauv thaum ntxov lactation nyob rau hauv PP nyuj piv rau cov MP nyuj, txuam nrog tsis muaj zog ua ntej ntawm cov as-ham rau lub caj pas mammary, yog li tso cai rau kev loj hlob ntxiv. Cov noob qhia cov ntaub ntawv nyob rau hauv circulating leukocytes kuj txawv ntawm PP thiab MP nyuj thaum ntxov lactation [33].

Desert ginseng-Improve immunity (23)

cistanche tubulosa- txhim kho lub cev tiv thaiv kab mob

Kev tswj kev noj zaub mov kom zoo thaum lub sij hawm qhuav tuaj yeem ua rau kom noj cov khoom qhuav (DMI), txo qhov tshwm sim ntawm tus kab mob periparturient, thiab txhim kho fertility [34]. Muaj cov lus qhia dav dav rau yuav ua li cas txo cov kab mob cuam tshuam txog kev noj zaub mov thiab kev tswj hwm [35]. Txawm li cas los xij, muaj cov ntaub ntawv me me muaj nyob rau ntawm cov qauv kev noj haus rau tus neeg nyuj nyob rau hauv ib qho metabolic tsis txaus thaum lub sij hawm tom qab yug me nyuam uas tuaj yeem txhim kho kev tiv thaiv kab mob, txo cov kab mob, thiab txhim kho kev ua me nyuam tom qab. Kev tsim cov khoom noj uas muaj peev xwm noj tau zoo yog qhov ua tau zoo [36]. Nyob rau hauv txoj kev tshawb no, nyuj nyob rau hauv thaum ntxov lactation muaj tsawg (LC), nruab nrab (MC), los yog siab concentrate (HC) noj raws li proportions ntawm concentrate rau nyom silage, thiab cuam tshuam rau metabolic noj qab haus huv thiab kab mob, thiab kev tiv thaiv kab mob ( los ntawm kev soj ntsuam thoob ntiaj teb ncig leukocyte noob qhia profiles) tau txiav txim siab. Cov ntaub ntawv los ntawm PP thiab MP nyuj raug txheeb xyuas cais kom tsis txhob muaj qhov cuam tshuam tsis zoo tshwm sim los ntawm kev sib luag. Peb qhov kev xav yog tias kev noj zaub mov muaj ntau ntau yuav txhim kho kev tiv thaiv kab mob thiab muaj txiaj ntsig fertility.

Desert ginseng-Improve immunity (2)

cistanche tubulosa- txhim kho lub cev tiv thaiv kab mob

2. Cov txiaj ntsig

2.1. Cov txiaj ntsig ntawm Kev Noj Qab Haus Huv ntawm Kev Noj Qab Haus Huv qhuav, Mis tawm los, Lub zog sib npaug thiab cov ntshav metabolites

Cov mis nyuj tsis, lub cev hnyav (BW), DMI, tus qhab nia ntawm lub cev (BCS), lub zog sib npaug (EBAL), thiab cov ntshav metabolites rau MP thiab PP nyuj nyob ib ncig ntawm 14 hnub hauv cov mis nyuj (DIM) tau sau tseg hauv Table 1. DMI rau MP nyuj sib txawv heev ntawm peb pawg neeg noj zaub mov nrog kev txiav txim ntawm HC > MC > LC (p < 0 0}1– 0 0{{11 }}1). Cov kua mis tawm hauv MP nyuj tau txais HC cov zaub mov muaj ntau dua li cov uas tau txais cov khoom noj LC (p < 0.05). Qhov sib txawv ntawm lub zog kho cov kua mis tawm (ECM) ntawm pawg LC thiab HC yog qhov tseem ceeb (p < 0.05), nrog rau cov txiaj ntsig nruab nrab hauv pawg MC. Cov txiaj ntsig EBAL hauv tag nrho peb pawg MP yog qhov tsis zoo tab sis cov hauv MC thiab HC nyuj tau zoo dua (tsawg dua qhov tsis zoo) dua li hauv LC nyuj (p <0.01). Cov circulating concentrations ntawm ob qho tib si qabzib (p < 0.01) thiab IGF-1 (p < 0.001) nyob rau hauv HC nyuj yog ho ntau dua nyob rau hauv LC nyuj. Cov MP nyuj muaj HC cov zaub mov kuj tsim cov urea tsawg dua (p < 0.001), BHB (p < 0.05), thiab NEFAs dua li cov khoom noj LC nrog cov concentrations LC> MC> HC, txawm hais tias qhov sib txawv ntawm NEFA concentrations ntawm pawg neeg noj zaub mov. tsis tau txheeb xyuas qhov tseem ceeb.

Table 1. Tag nrho cov khoom qhuav qhuav, tsis muaj mis nyuj, lub cev hnyav, lub zog sib npaug, cov qhab nia ntawm lub cev, thiab cov ntshav metabolites nyob ib ncig ntawm 14 hnub tom qab calving, soj ntsuam raws li parity thiab noj 1,2

Table 1. Total dry matter intakes, milk parameters, body weights, energy balance, body condition score, and blood metabolites at around 14 days after calving, analyzed according to parity and diet 1,2

Hauv PP nyuj, cov uas tau txais MC lossis HC noj zaub mov muaj DMI siab dua cov uas tau txais LC noj (p < {{0}}}01). Mis yields tsis txawv heev. EBAL tau zoo nyob rau hauv nyuj muab MC lossis HC cov zaub mov thaum rau cov neeg tau noj LC, nws tsis zoo. Qhov sib txawv ntawm EBAL ntawm HC thiab LC PP nyuj yog qhov tseem ceeb (p <0.05). Ntawm cov metabolites ntsuas, tsuas yog urea concentration sib txawv ntawm cov pab pawg, ua qis dua hauv HC nyuj (LC> MC> HC, p < 0.001 rau LC vs. HC lossis MC).

2.2. Cov txiaj ntsig ntawm Kev Noj Qab Haus Huv rau Cov Kab Mob Kab Mob

Cov teebmeem ntawm kev noj zaub mov ntawm cov kab mob inflammatory uas ntsuas nyob rau hauv lub tsev menyuam thiab cov qog mammary tau nthuav tawm hauv Table 2. Hauv PP nyuj, qhov piv ntawm polymorphonuclear leukocytes rau uterine epithelial cells (PMNs: UECs) sau los ntawm lub tsev menyuam uas siv lub cytobrush tau ntau dua rau cov nyuj ntawm HC piv nrog LC noj (p < 0.05). Hauv MP nyuj, qhov sib txawv yog nyob rau hauv tib txoj kev, nrog LC < MC < HC, tab sis tsis ua tiav qhov tseem ceeb. Hauv cov mis nyuj, MP nyuj ntawm LC noj zaub mov muaj SCC ntau dua li cov khoom noj ntawm MC lossis HC (p < 0.05), hos hauv PP nyuj qhov tsis tseem ceeb yog qhov sib txawv. . Mis N-acetyl- -d-glucosaminidase (NAGase) thiab lactate dehydrogenase (LDH) concentrations, mis nyuj enzymes qhia txog mastitis, ua raws li cov qauv dav dav raws li SCC qhov tseem ceeb tab sis tsis muaj qhov sib txawv tseem ceeb. Cov txiaj ntsig no tau txais kev txhawb nqa los ntawm cov ntaub ntawv kho mob. MP nyuj ntawm HC noj zaub mov tsis tau muaj mob mastitis (0/15) whereas 4/14 (28.6%) ntawm nyuj ntawm LC noj zaub mov tau kuaj mob mastitis nyob rau hauv 16 hnub ntawm calving. Cov qauv tau rov ua dua rau qhov sib txawv rau PP nyuj nrog rau ib qho ntawm rau (16.7%) ntawm LC noj zaub mov nrog kev kho mob mastitis piv nrog rau ib kis ntawm kev kho mob thiab ob ntawm subclinical mastitis ntawm HC noj (50%).

Table 2. Cov kab mob o nyob ib ncig ntawm 14 hnub tom qab calving raws li parity thiab noj 1,2.

Table 2. Inflammatory parameters at around 14 days after calving according to parity and diet 1,2.

2.3. Cov ntaub ntawv Fertility

Cov ntsiab lus ntawm cov ntaub ntawv fertility yog muab nyob rau hauv Table 3. Rau MP nyuj, cov nyob rau hauv LC noj zaub mov siv sij hawm ntev me ntsis kom xeeb tub thiab xav tau ntau cov kev pab cuam ib conception tshaj HC nyuj (2.4 ± 0.42 vs. 1.6 ± 0.23), txawm hais tias ntau tus nyuj HC tsis tau ua haujlwm (kev txiav txim siab tswj hwm) lossis tsis xeeb tub txhua (6{{10}}}0% vs 71.4%). Tsis muaj qhov sib txawv no, txawm li cas los xij, tseem ceeb. Rau PP nyuj, qhov thim rov qab yog qhov tseeb, nrog rau LC nyuj muaj lub sijhawm luv tshaj plaws rau kev xeeb tub los ntawm 29 hnub (p < {{20}}.05), nrog tsib ntawm rau tus tsiaj xeeb menyuam thawj zaug. . Hauv qhov sib piv, ib nrab ntawm HC pab pawg tsis tau txais kev pabcuam (n=2) lossis ua tsis tiav (n=1), nrog rau peb qhov uas tau xeeb tub yuav tsum muaj 2.0 ± 0.41 kev pabcuam rau ib qho kev xav. Qhov no ua rau pawg HC muaj qhov siab dua "hauv calf los ntawm" (ICB) qhab nia (p <0.05).

Table 3. Fertility data raws li parity thiab noj 1,2

Table 3. Fertility data according to parity and diet 1,2

2.4. Leukocyte Transcriptomic Profiles nyob rau hauv nyuj muaj ntau yam sib txawv ntawm kev xav

Cov ntaub ntawv siv bovine genome ntawm ARS-UCD 1.2 muab los ntawm RefSeq (https://www. ncbi.nlm.nih.gov/assembly, nkag rau 1 Tsib Hlis 2022) muaj 35,158 cov noob, ntawm 19,001 leukocyte genes tau quantifiable thaum nyeem cov sequencing. nyob rau hauv cov ntaub ntawv FASTQ tau mapped rau nws. Cov phiaj xwm hluav taws xob uas qhia cov lus qhia hauv MP thiab PP nyuj tau txais peb qhov kev noj haus sib txawv tau nthuav tawm hauv daim duab 1. Hauv MP nyuj, muaj 173 qhov sib txawv ntawm cov noob (DEGs) hauv kev sib piv ntawm HC thiab LC, 126 ntawm MC thiab LC, thiab 68 rau HC vs. MC (Cov Ntaub Ntawv Ntxiv S1A–C). Venn daim duab qhia tau hais tias tsis muaj noob (feem ntau DEG) yog qhov tseem ceeb hauv tag nrho peb qhov kev sib piv kev noj haus (Daim duab 2A). Hauv PP nyuj, muaj 460 DEGs hauv kev sib piv ntawm HC vs. LC, 178 ntawm MC vs. LC, thiab 128 ntawm HC vs. MC (Cov Ntaub Ntawv Ntxiv S2A–C). Tsuas yog ib hom noob (DCN, hloov pauv (FC)=−7.3) yog qhov tseem ceeb hauv peb qhov kev sib piv kev noj haus (Daim duab 2B). Qhov no encodes decorin, ib qho protein uas ua lub luag haujlwm hauv collagen fibril los ua ke. Zuag qhia tag nrho nws pom tau hais tias ntau dua ntawm DEGs tau pom nyob rau hauv kev sib piv kev noj haus ntawm leukocyte noob qhia hauv PP dua li hauv MP nyuj txawm tias cov pab pawg me me, nrog rau feem ntau ntawm cov noob no raug kho ntawm HC noj. Tsis tas li ntawd, muaj kev sib tshooj me me ntawm cov noob uas tau txheeb xyuas ntawm cov hnub nyoog sib txawv, raws li tau piav qhia hauv Venn daim duab hauv daim duab 3. Qhov no qhia tias cov khoom noj muaj qhov sib txawv ntawm leukocyte transcriptome hauv PP thiab MP nyuj. Hauv ob pawg hnub nyoog, qhov sib txawv loj tshaj plaws ntawm cov nyuj tau muab cov khoom noj LC thiab HC, yog li peb tsom rau qhov kev sib piv no hauv kev tshuaj ntsuam tom ntej.

Daim duab 1. Cov phiaj xwm hluav taws xob qhia cov lus qhia hauv MP thiab PP nyuj tau txais peb yam khoom noj sib txawv. (A) MP nyuj HC vs. LC, (B) MP nyuj HC vs. MC, (C) MP nyuj MC vs. LC, (D) PP HC vs. LC, (E) PP HC vs. MC thiab (F ) PP MC vs. LC. HC: siab concentrate (n=6 hauv PP nyuj thiab n=14 hauv MP nyuj), MC: nruab nrab concentrate (n=5 hauv PP nyuj thiab n=15 hauv MP nyuj ), thiab LC: qis concentration (n=6 hauv PP nyuj thiab n=14 hauv MP nyuj). Cov kev hloov pauv tau teev tseg 2- hloov pauv. Cov dots ntsuab qhia cov noob caj noob ces nrog p (BH) < 0.05 thiab hloov pauv tsawg dua lossis sib npaug rau −1.5 thiab cov dots liab qhia txog cov noob caj ces nrog p (BH) < {{ 16}}.05 thiab hloov pauv ntau dua lossis sib npaug rau 1.5. Cov txiv kab ntxwv dots qhia cov noob nrog p (BH) < 0.05 tab sis qhov tseeb fold hloov < 1.5.

Figure 2. Venn diagrams showing the differentially expressed genes by the circulating leukocytes between the three dietary groups in (A) multiparous (MP) cows and (B) primiparous (PP) cows. HC: high concentrate (n = 6 in PP cows and n = 14 in MP cows), MC: medium concentrate (n = 5 in PP cows and n = 15 in MP cows) and LC: low concentrate (n = 6 in PP cows and n = 14 in MP cows).

Daim duab 2. Venn daim duab qhia qhov txawv ntawm cov noob los ntawm cov leukocytes ncig ntawm peb pawg noj zaub mov hauv (A) multiparous (MP) nyuj thiab (B) primiparous (PP) nyuj. HC: siab concentrate (n=6 hauv PP nyuj thiab n=14 hauv MP nyuj), MC: nruab nrab concentrate (n=5 hauv PP nyuj thiab n=15 hauv MP nyuj ) thiab LC: qis concentration (n=6 hauv PP nyuj thiab n=14 hauv MP nyuj).

Figure 3. Venn diagrams showing the differentially expressed genes by circulating leukocytes between the PP and MP cows in the comparisons of (A) high concentrate (HC) with low concentrate (LC); (B) HC with medium concentrate (MC), and (C) MC with LC. HC: n = 6 in PP cows and n = 14 in MP cows, MC: n = 5 in PP cows and n = 15 in MP cows and LC: n = 6 in PP cows and n = 14 in MP cows

Daim duab 3. Venn daim duab qhia qhov sib txawv ntawm cov noob los ntawm kev nthuav tawm cov leukocytes ntawm PP thiab MP nyuj nyob rau hauv qhov sib piv ntawm (A) siab concentrate (HC) uas tsis muaj concentrate (LC); (B) HC nrog nruab nrab concentrate (MC), thiab (C) MC nrog LC. HC: n=6 hauv PP nyuj thiab n=14 hauv MP nyuj, MC: n=5 hauv PP nyuj thiab n=15 hauv MP nyuj thiab LC: n {{5 }} hauv PP nyuj thiab n=14 hauv MP nyuj

2.5. Kev sib piv ntawm Leukocyte Gene Expression Profiles ntawm Multiparous nyuj tau txais kev noj zaub mov siab lossis qis qis

Sab saum toj 20 upregulated thiab downregulated DEGs ranked los ntawm p qhov tseem ceeb (BH kho) nyob rau hauv cov MP nyuj pub ib HC piv nrog cov uas pub ib tug LC noj zaub mov yog muab nyob rau hauv Supplementary File S1D, E. Ntawm cov upregulated DEGs, feem ntau tau koom nyob rau hauv lub GO kev ua haujlwm ntawm cov txheej txheem tiv thaiv kab mob, cov metabolism, thiab cov lus teb rau kev txhawb nqa, nrog ntau cov proteins encoding muaj ntau lub luag haujlwm. Piv txwv li, ALAS2 (encoding 50 -aminolevulinate synthase 2) muaj lub luag haujlwm hauv cov txheej txheem metabolic, cov lus teb rau kev txhawb nqa, thiab kev loj hlob. COL1A1 (collagen type I alpha 1 chain) thiab DAB2 muaj kev koom tes hauv cov metabolism, cov lus teb rau stimulus, multicellular kab mob, locomotion, thiab kev loj hlob. Sab saum toj 20 downregulated noob qhia txog lub ntsiab lus meej ntawm kev hloov hauv kev tiv thaiv nrog 14 txuam DEGs. Ntawm cov no, DMTB1, FGA, FGB, thiab TF encode antimicrobial peptides, ALB thiab TF encode tsis zoo rau theem proteins (APP), thiab FGA thiab FGG encode zoo APPs. Yim lub noob ua lub luag haujlwm hauv cov metabolism thiab 10 koom nrog hauv kev teb rau kev txhawb nqa.

Desert ginseng-Improve immunity (15)

cistanche cog-nce kev tiv thaiv kab mob

Cov leukocyte DEGs tau los ntawm kev sib piv ntawm HC nrog pab pawg LC tom ntej yuav raug rau GO enrichment tsom xam. Lub 76 upregulated DEGs tau ua kom muaj txiaj ntsig zoo nrog 208 lub luag haujlwm, ntawm 20 sab saum toj raws li cov qhab nia ntxiv tau pom hauv daim duab 4A. Cov no tau cuam tshuam nrog ntau yam ntawm kev ua haujlwm ntawm tes, nrog platelet muab los ntawm kev loj hlob zoo los khi rau saum. Muaj ntau lub zog muaj feem xyuam rau cov protein thiab amino acid metabolism (xws li APLP1, COL1A1, COL1A2, COL3A1, HTR1B, thiab P2RY12 feem ntau), biomineralization thiab collagen ua (suav nrog COL1A1, COL1A2, SPP1, thiab TUFT1), thiab kev sib txuas lus ntawm tes. Hauv qhov sib piv, cov haujlwm saum toj kawg nkaus ntawm 97 downregulated DEGs muaj lub ntsiab lus meej ntawm ntau yam txheej txheem tiv thaiv kab mob (Daim duab 4B) uas feem ntau cuam tshuam nrog 20 DEGs. Ntawm cov no, FGA (zoo APP) tau txo qis los ntawm 85-fold hauv HC vs. LC kev sib piv. Ib lub cuab yeej GO browser tau sau tseg cov haujlwm lom neeg ntawm ob qho tib si nce thiab nqis tswj DEGs rau yim pawg tseem ceeb (Table 4). Tsuas yog rau biomineralization, tag nrho lwm yam kev ua haujlwm lom neeg, tshwj xeeb tshaj yog cov cuam tshuam nrog kev tiv thaiv kab mob, feem ntau cuam tshuam nrog kev txo qis ntawm DEGs.

Figure 4. Top 20 GO functions associated with the DEGs derived from HC vs. LC comparisons. (A) MP upregulated DEGs, (B) MP downregulated DEGs, (C) PP upregulated DEG and (D) PP downregulated DEGs.

Daim duab 4. Sab saum toj 20 GO functions txuam nrog DEGs muab los ntawm HC thiab LC kev sib piv. (A) MP upregulated DEGs, (B) MP downregulated DEGs, (C) PP upregulated DEG thiab (D) PP downregulated DEGs.

Table 4. Cov ntsiab lus ntawm GO enrichment lub luag haujlwm tseem ceeb ntawm leukocyte DEGs nyob rau hauv kev sib piv ntawm cov nyuj multiparous tau txais siab (n=14) thiab qis (n=14) noj cov zaub mov thaum ntxov lactation.

Table 4. Summary of GO enrichment main functions of leukocyte DEGs in the comparison between the multiparous cows receiving high (n = 14) and low (n = 14) concentrate diets in early lactation.

Table 4. Cont.

Kev sib xyaw ua ke thiab txo qis DEGs (n=173) tau ua kom muaj txiaj ntsig zoo nrog 23 KEGG txoj hauv kev uas feem ntau cuam tshuam nrog ntau yam kev tiv thaiv kab mob thiab cov txheej txheem metabolic (Table 5). Ntxiv thiab coagulation cascades nyob rau sab saum toj nrog yim downregulated DEGs (CFB, FGA, FGB, FGG, KNG1, PROC, SERPINA1, thiab VTN). Txoj kev inflammatory ntawm NOD-zoo li signaling tau txuam nrog rau DEGs (IFNB1, MAPK10, OAS1X, OAS1Y, OAS1Z, thiab OAS2), uas tag nrho tab sis MAPK10 tau downregulated. Txoj hauv kev ntawm kev zom cov protein thiab nqus tau muaj rau DEGs, ntawm qhov uas peb (COL1A1, COL1A2, thiab COL3A1) tau raug tswj xyuas thiab peb qhov txo qis (CELA2A, COL5A3, thiab ELN). Tsib downregulated DEGs tau koom nrog hauv peroxisome proliferator-activated receptors (PPARs) kev taw qhia txoj hauv kev (APOA2, APOC3, FABP1, HMGCS2, thiab PCK1). Txoj hauv kev ntawm extracellular matrix-receptor kev sib cuam tshuam, focal adhesion, thiab sphingolipid signaling yog txhua tus koom tes hauv kev saib xyuas ntawm tes thiab cov ntaub so ntswg.

Table 5. Txoj hauv kev tseem ceeb uas tau txheeb xyuas los ntawm KEGG txoj hauv kev txhawb nqa cuam tshuam nrog qhov sib txawv ntawm cov leukocyte cov noob nyob rau hauv cov nyuj multiparous muaj cov khoom noj muaj siab (n=14) piv nrog cov uas tau noj cov zaub mov tsis tshua muaj siab (n=14).

Table 5. Significant pathways identified by KEGG pathway enrichment associated with differentially expressed leukocyte genes in the multiparous cows offered the high concentrate diet (n = 14) compared with those offered the low concentrate diet (n = 14).

2.6. Kev sib piv ntawm Leukocyte Gene Expression Patterns ntawm Primiparous nyuj tau txais kev noj zaub mov siab lossis qis qis

Sab saum toj 20 circulating leukocyte DEGs nyob rau hauv PP nyuj pub HC piv nrog cov LC cov zaub mov muaj npe nyob rau hauv Ntxiv Cov Ntaub Ntawv S2D, E. Immune, thiab cov txheej txheem metabolic predominated cov roj ntsha muaj nuj nqi ntawm cov upregulated DEGs, muaj 11 thiab 12 DEGs feem. Ntawm cov no, ACSL6, MMP9 thiab SLC11A1 tau koom nrog hauv leukocyte proliferation, thiab ACSL6, ADGRG3, COL1A2, DUSP1, HCK, MMP9 thiab PADI4 hauv txoj kev loj hlob. SLC40A1 yog tus thauj hlau loj uas ua lub luag haujlwm tseem ceeb hauv kev ntsuas cov cellular thiab cov txheej txheem hlau. Qee qhov DEGs no encode proteins nrog ntau lub luag haujlwm. Piv txwv li, MMP9, DUSP1, SLC11A1, thiab COL1A2 yog txuam nrog feem ntau ntawm cov haujlwm saum toj no GO. Cov kev ua haujlwm lom neeg ntawm cov txheej txheem saum toj kawg nkaus ntawm DEGs muaj ntau haiv neeg. Muaj yim DEGs koom nrog hauv cov txheej txheem tiv thaiv kab mob, tsib lub luag haujlwm hauv cov metabolism, thiab ob qho cuam tshuam nrog ob qho tib si leukocyte proliferation thiab txoj kev loj hlob (EPCAM thiab FCRL3). Ib zaug ntxiv, qee qhov DEGs, piv txwv li CD96 thiab FCRL3, encode proteins nrog ntau lub luag haujlwm.

Hauv PP nyuj, 382 upregulated DEGs muab los ntawm HC vs. LC kev sib piv tau cuam tshuam nrog 690 GO functions, nrog rau sab saum toj 20 qhia hauv daim duab 4C. Tag nrho cov no koom nrog 116 DEGs (Cov Ntaub Ntawv Ntxiv S2F) nrog ntau yam kev tiv thaiv kab mob. Cov haujlwm saum toj kawg nkaus yog lub xov tooj ntawm tes receptor signaling txoj hauv kev. Qhov no tau txuam nrog 43 DEGs uas suav nrog cov noob encoding ntau receptors rau lub cev tiv thaiv kab mob, xws li CXCR1, CXCR2, IL17RD, thiab IL1RAP. Qhov kev ua haujlwm no muaj rau lub luag haujlwm tseem ceeb suav nrog lipopolysaccharide (LPS)-kho cov teeb liab txoj hauv kev (PTAFR, TLR4, thiab SCARB1) thiab lub cev tiv thaiv kab mob tiv thaiv kab mob ntawm cov cell nto receptor signaling pathway. Qhov kev ua haujlwm siab tshaj plaws nyob rau hauv kev tswj hwm ntawm cov txheej txheem ntau lub cev yog kev tswj hwm ntawm cytokine ntau lawm, nrog 24 upregulated DEGs, xws li MARK13, LTF, thiab TLR4. Muaj tsawg dua kev tswj hwm DEGs (tsuas yog 78) uas tau cuam tshuam nrog 298 qhov tseem ceeb GO lub luag haujlwm, nrog cov qhab nia qis dua thiab ntau cov txheej txheem lom neeg. Daim duab 4D qhia txog 20 lub luag haujlwm saum toj kawg nkaus. Ib tug xov tooj ntawm cov no tau txuam nrog cov yam ntxwv ntawm kev tiv thaiv kab mob, xws li cell adhesion, kev tswj hwm ntawm kev tsim cov neeg nruab nrab ntawm lub cev tiv thaiv kab mob, cov lus teb rau LPS, thiab cov lus teb rau cov kab mob ntawm cov kab mob. Lwm tus tau cuam tshuam txog kev saib xyuas homeostasis, xws li cell nto, cytolysis, transmembrane thauj, thiab serine-type endopeptidase. Cov ntsiab lus tseem ceeb ntawm kev ua haujlwm lom neeg muaj feem cuam tshuam nrog ob qho tib si nce thiab txo qis DEGs tau tsim xya pawg (Table 6), nrog rau cov txheej txheem tiv thaiv kab mob rau sab saum toj thiab feem ntau ntawm lwm cov haujlwm tseem cuam tshuam nrog kev tiv thaiv kab mob. Piv txwv li, locomotion tau enriched los ntawm DEGs nrog chemotactic thiab tiv thaiv kab mob thiab interspecies kev sib cuam tshuam ntawm cov kab mob, uas muaj feem xyuam rau tua invaded pathogens. Ob leeg txheej txheem ntawm tes thiab kev tswj kev lom neeg tau cuam tshuam nrog ntau tus DEGs. Cov txheej txheem ntawm tes (n=239 DEGs) suav nrog ntau cov haujlwm ua haujlwm cuam tshuam nrog kev sib txuas ntawm tes, kev tua ntawm tes, kev ua kom lub cev tiv thaiv kab mob, thiab kev loj hlob ntawm cov neeg ntawm tes. Kev tswj hwm kev noj qab haus huv (125 DEGs) kuj muaj ntau yam kev tiv thaiv kab mob, xws li kev tswj hwm lub cev tiv thaiv kab mob, kev txav chaw, thiab teb rau kev txhawb nqa. Tag nrho cov haujlwm no muaj feem ntau tswj hwm DEGs ntawm HC noj zaub mov.

Table 6. Cov ntsiab lus ntawm GO enrichment lub luag haujlwm tseem ceeb ntawm DEGs hauv kev sib piv ntawm cov nyuj primiparous muab cov siab (n=6) thiab qis (n=6) noj cov zaub mov thaum ntxov lactation.

Table 6. Summary of GO enrichment main functions of DEGs in the comparison between the primiparous cows offered the high (n = 6) and low (n = 6) concentrate diets in early lactation.

Table 6. Cont.

Kev sib xyaw ua ke thiab txo qis DEGs (460) hauv PP nyuj tau ntxiv nrog 35 txoj hauv kev tseem ceeb KEGG (Table 7). Ntau yam tau cuam tshuam nrog cov txheej txheem metabolic uas muaj cov amino acids (valine, leucine, isoleucine, arginine, thiab glutathione), proteins, lipids (arachidonic acid, glycerollipid, thiab roj cholesterol), vitamin B6, thiab qee cov tshuaj hormones (aldosterone, cortisol, thyroid thiab loj hlob hormones. ). Cov txheej txheem metabolic no feem ntau ua kom muaj txiaj ntsig zoo nrog DEGs upregulated ntawm HC noj. Piv txwv li, biosynthesis ntawm amino acids yog txuam nrog tsib upregulated DEGs (ARG2, ASS1, GPT2, SDS, thiab SDSL), txoj kev loj hlob hormone synthesis, secretion, thiab kev ua tau enriched nrog rau upregulated (ADCY6, CREB3L2, CREB5, FOS. , MAPK13 thiab SOCS3) thiab ib qho downregulated (BCAR1) DEGs, thiab arachidonic acid metabolism muaj tsib upregulated DEGs (CYP2J2, GGT5, GPX3, PLB1 thiab TBXAS1). Ntau txoj hauv kev cuam tshuam nrog cov txheej txheem tiv thaiv kab mob / inflammatory kuj tseem muaj txiaj ntsig zoo, ntxiv nrog rau kev tswj hwm DEGs. Cov no suav nrog chemokine, MAPK, thiab TNF qhia txoj hauv kev thiab ntxiv thiab coagulation cascades. Piv txwv li, chemokine signaling pathway muaj yim upregulated (ADCY6, CCL16, CCR1, CXCL13, CXCR1, CXCR2, GNG7, thiab HCK) thiab ob downregulated DEGs (BCAR1 thiab CCR5), TNF signaling pathway muaj rau upregulated DEGs (CREB5L2, , FOS, MAPK13, MMP9, thiab SOCS3), thiab MAPK cov cim qhia txoj hauv kev muaj 12 upregulated DEGs, suav nrog IL1A, MAP3K6 thiab MAPK13.

Table 7. Txoj hauv kev tseem ceeb uas tau txheeb xyuas los ntawm Kegg txoj hauv kev txhawb nqa cov txiaj ntsig sib txawv ntawm cov noob leukocyte sib txawv hauv cov nyuj primiparous tau muab cov khoom noj muaj zog siab (n=6) piv nrog cov uas tau noj cov zaub mov tsis tshua muaj siab (n=6).

Table 7. Significant pathways identified by Kegg pathway enrichment associated with differentially expressed leukocyte genes in the primiparous cows offered the high concentrate diet (n = 6) compared with those offered the low concentrate diet (n = 6).

3. Kev sib tham

Cov nyuj tom qab yug me nyuam muaj homeostatic mechanisms los tswj cov khoom noj sib faib ntawm lactation thiab lwm yam tseem ceeb hauv lub neej, xws li kev tiv thaiv kab mob thiab kev loj hlob [8]. Cov ntaub so ntswg mob yog ib qho kev hloov pauv ntawm cov tsiaj nyeg los txhawb kev lactation, tab sis qee tus nyuj ua metabolically imbalanced [35,37]. Cov tsiaj zoo li no tau dhau los ua cov ntaub so ntswg adipose, tiv thaiv insulin, thiab cov kab mob hauv lub cev uas ua rau lub cev tsis muaj zog feem ntau pom nyob rau lub sijhawm no [38]. Qhov no yog txuam nrog inflammatory mediators xws li TNF thiab IL6 [39,40]. Nyob rau hnub 14 tom qab calving, thaum lub circulating leukocyte kuaj nyob rau hauv qhov kev tshawb fawb no tau sau, lub hlwb thiaj li raug mus rau ib lub sij hawm ntawm inflammatory stimulation. Peb tau ua kom pom kev siv cov tiam tom ntej thiab kev soj ntsuam bioinformatics tias cov khoom noj uas muaj ntau qhov sib txawv ntawm cov ntsiab lus ua rau muaj kev cuam tshuam sib txawv ntawm cov leukocyte transcriptome hauv PP thiab MP nyuj thaum ntxov lactation. Qhov no tau cuam tshuam nrog qhov sib txawv ntawm lawv txoj kev noj qab haus huv thiab fertility. Cov ntaub ntawv no tau ntxiv cov kev tshawb pom tshiab rau peb daim ntawv tshaj tawm dhau los ntawm kev noj haus ntawm cov mis nyuj thiab kev tiv thaiv kab mob [32].

3.1. Kev sib piv ntawm cov txiaj ntsig ntawm Kev Noj Qab Haus Huv Siab thiab qis qis hauv Multiparous nyuj

MP nyuj ntawm HC cov zaub mov muaj DMI siab dua MC thiab LC nyuj thiab qhov no tau cuam tshuam nrog ntau dua circulating concentrations ntawm ob qho tib si qabzib thiab IGF{{0}}}. Qhov no ua rau HC nyuj nyob hauv NEB hnyav dua thiab tsim cov mis nyuj ntau dua. Kev noj zaub mov HC tau tsim los ua kom tau raws li qhov xav tau ntawm lub zog thiab cov protein ntau rau kev lactation thiab kev saib xyuas ntawm lub cev homeostasis thiab cov kev ntsuas metabolite tau lees paub tias lawv cov txheej txheem metabolic tau zoo dua li rau LC nyuj, nrog rau kev xav tau tsawg dua rau cov ntaub so ntswg kom tau raws li qhov xav tau ntawm lub zog. Qhov no yuav tsum tau pab kom ceev cov kev daws teeb meem ntawm postpartum inflammatory txheej txheem, raws li muaj ntau inflammatory kab mob nyob rau hauv thaum ntxov lactation yog txuam nrog los yog tshwm sim los ntawm metabolic ntshawv siab [38] thiab peb tau pom yav tas los hais tias uterine o tau daws sai dua nyob rau hauv nyuj nrog ib tug zoo zog tshuav nyiaj li cas. [2]. Hauv kev tshawb fawb tam sim no, tsis muaj qhov sib txawv ntawm qhov piv ntawm PMNs rau cov hlwb epithelial hauv lub tsev menyuam lumen raws li kev noj zaub mov hauv MP nyuj. Qhov kev ntsuas no feem ntau coj los ua qhov qhia txog cytological endometritis [41]. Qhov sib txawv raws li kev noj haus tau, txawm li cas los xij, pom nyob rau hauv lub caj pas mammary vim LC nyuj muaj SCC siab dua thiab qhov no tau cuam tshuam nrog ntau dua ntawm lawv tau ntsib kev kho mob mastitis thaum thawj 16 DIM (28.6% vs. 0% hauv LC vs. . HC pawg).

Feem ntau ntawm DEGs tau txheeb xyuas hauv kev tshuaj xyuas ntawm leukocyte transcriptome tau koom nrog hauv kev tiv thaiv kab mob thiab / lossis cov txheej txheem metabolic, raws li xav tau hauv cov neeg tiv thaiv kab mob. Txoj hauv kev tseem ceeb tshaj plaws ntawm KEGG yog qhov sib ntxiv thiab coagulation cascade, uas suav nrog rau ntawm cov noob qis tshaj plaws hauv HC nyuj. Ntawm no, CFB encodes complement factor B, ib feem ntawm lwm txoj hauv kev ntawm kev ua kom tiav. FGA, FGB, thiab FGG encode peb subunits ntawm coagulation factor fibrinogen, ib feem tseem ceeb ntawm cov ntshav txhaws uas tseem ceeb heev nyob rau hauv khi cov kab mob rau platelets [42]. Lub siab molecular hnyav daim ntawv ntawm kininogen, encoded los ntawm KNG1, kuj yog ib qho tseem ceeb rau cov ntshav coagulation, thiab kininogen tso bradykinin, peptide nrog ntau lub zog nrog rau kev ua haujlwm ntawm cov kab mob thiab tshuaj tua kab mob. Vitronectin, encoded los ntawm VTN, tseem koom nrog hauv kev tswj hwm txoj hauv kev coagulation thiab kho qhov txhab, thaum nws cov heparin-binding domain muab cov khoom tiv thaiv kab mob. PROC encodes plasma glycoprotein uas nws daim ntawv qhib muaj cov serine protease domain uas ua haujlwm hauv kev degradation ntawm cov ntaub ntawv ua kom muaj coagulation yam V thiab VIII, thaum SERPINA1 encodes serine protease inhibitor uas nws lub hom phiaj muaj xws li plasmin, thrombin, thiab plasminogen activator. Upregulation ntawm complement thiab coagulation cascade yav tas los tau pom nyob rau hauv cov ntaub so ntswg mammary raws li tus tswv tsev thaum ntxov teb rau E. coli los yog Staph. aureus kab mob [43] Raws li txoj hauv kev no tau nthuav tawm ntau dua hauv cov nyuj ntawm LC noj zaub mov, qhov no txhawb nqa cov pov thawj ntawm qhov tshwm sim ntau dua ntawm mastitis hauv cov tsiaj no.

Desert ginseng-Improve immunity (23)

cistanche tubulosa- txhim kho lub cev tiv thaiv kab mob

Lwm qhov kev ua haujlwm saum toj kawg nkaus tau sau tseg los ntawm GO browser yog cov txheej txheem tua kab mob (kev sib cuam tshuam ntawm cov kab mob), uas tau cuam tshuam nrog 14 qhov kev txwv tsis pub DEGs hauv HC nyuj (Table 4). Qhov no suav nrog ntau cov noob caj noob ces koom nrog hauv kev ua haujlwm tiv thaiv kab mob (IFI6, IFNB1, ISG15, MX2, OAS1Y, OAS1Z, OAS2, thiab RSAD2) uas tau qhia nyob rau theem qis. Ntawm cov no, IFNB1 encodes interferon beta 1 thaum lwm tus yog tag nrho cov interferon-stimulated noob [44,45]. Lawv tag nrho kuj yog ib feem ntawm NOD-zoo li receptor (NLR) kev taw qhia txoj hauv kev. NLRs yog cytosolic pattern recognition receptors uas tau qhib los ntawm ntau yam tsis-tus kheej-khoom nrog nrog rau cov kab mob peptidoglycan, muaj peev xwm pib NF-kappa B-/AP-1- nyob ntawm kev qhia ntawm pro-inflammatory cytokines, qhia hom I interferons, autophagy thiab kev kho mob [46]. Peb txoj kev tshawb fawb tsis ntev los no tau pom tias txoj hauv kev no tau hloov kho hauv cov leukocytes los ntawm cov nyuj uas muaj kab mob E. coli [47]. Lwm cov noob tau txheeb xyuas yog MPO, encoding myeloperoxidase, ib qho enzyme khaws cia hauv azurophilic granules ntawm PMNs thiab macrophages. Nws raug tso tawm rau hauv cov kua dej ntxiv thaum lub sijhawm ua haujlwm inflammatory thiab tau siv los ua tus cim ntawm kev mob thiab oxidative kev nyuaj siab [48]. IL1R2 encodes ib tug tswv cuab ntawm tsev neeg interleukin 1 receptor thiab yog ib qho ntawm feem ntau txo qis DEG pom nyob rau hauv MP nyuj. Qhov no tuaj yeem khi IL1A, IL1B, thiab interleukin 1 receptor, hom I (IL1R1 / IL1RA) tab sis ua raws li cov decoy receptor inhibit ligand kev ua haujlwm.

Cov noob uas muaj qhov sib txawv tseem ceeb tshaj plaws ntawm MP nyuj ntawm cov khoom noj sib txawv yog FCER1A, nrog kev qhia qis dua hauv HC nyuj. Qhov no encodes ib lub subunit ntawm IgE receptor, uas yog tus pib ntawm kev tsis haum tshuaj teb uas yuav tau hloov zuj zus los txhawb tus tswv tsev tiv thaiv kab mob los ntawm kev tso tawm cov neeg kho mob xws li histamine [49]. Interestingly, FCER1A yog ib qho ntawm 18 noob caj noob ces uas nws cov theem qhia tau pom tias yog kev ntxub ntxaug ntawm cov nqaij nyuj heifers [50]. Nws lub luag haujlwm meej hauv cov nyuj tseem tsis tau txiav txim siab tab sis hauv kev sim tshuaj tiv thaiv ntawm calves tau sim kis tus kab mob tseem ceeb ntawm cov kab mob parasitic nematode Ostertagia ostertagi, nws cov qib qhia hauv cov ntshav sib cuam tshuam zoo nrog mast cell suav thiab tsis zoo nrog cov kab mob [51]. Peb lwm cov noob caj noob ces hauv HC nyuj nrog qee qhov kev tiv thaiv kab mob yog ALAS2, GZMB, thiab LIF. ALAS2 encodes 50 -aminolevulinate synthase 2, ib qho erythroid-specific mitochondrially nyob enzyme uas catalyzes thawj thiab tus nqi-txheej kauj ruam hauv heme biosynthetic txoj kev. Heme yog ib qho tseem ceeb cofactor nyob rau hauv ntau yam txheej txheem tseem ceeb nrog rau kev thauj cov pa oxygen, thaum kev hloov pauv hauv cov noob no tau txuas nrog ntau yam kab mob ntawm tib neeg, suav nrog ntshav qab zib [52]. GZMB encodes ib tug preprotein uas yog secreted los ntawm tej yam ntuj tso killer hlwb thiab cytotoxic T lymphocytes thiab yog ua tiav los tsim ib tug nquag protease uas induces lub hom phiaj cell apoptosis thiab tseem ua cytokines thiab degrades extracellular matrix proteins [53]. Lub cytokine leukemia inhibitory yam tseem ceeb, encoded los ntawm LIF, tau pib pom los ntawm kev koom tes hauv kev sib txawv ntawm macrophage tab sis nws kuj tau pom tias ua lub luag haujlwm tseem ceeb hauv kev loj hlob ntawm embryo thiab tsim kev xeeb tub hauv ntau hom tsiaj nrog rau nyuj [54].

Cov DEGs tau muab los ntawm HC thiab LC kev sib piv hauv MP nyuj kuj tseem muaj ntau txoj hauv kev tseem ceeb cuam tshuam nrog cov piam thaj, protein, thiab fatty acid metabolism. Cov no suav nrog plaub qhov kev txwv tsis pub DEGs koom nrog PPAR txoj kev taw qhia (APOA2, APOC3, FABP1, thiab PCK1). Hauv txoj kev tshawb no, peb qhov loj PPAR isoforms (A, D, G) tau kuaj pom hauv cov neeg leukocyte. Txawm hais tias kev qhia ntawm PPARs lawv tus kheej tsis cuam tshuam los ntawm kev noj zaub mov, txoj hauv kev no tuaj yeem cuam tshuam rau kev qhia cov noob koom nrog hauv qabzib thiab lipid metabolism, kev sib txawv ntawm adipocytes, thiab cov lus teb inflammatory [55,56] thiab pab txhawb rau kev hloov pauv hauv metabolic rau cov khoom noj tsawg los ntawm inducing noob koom nrog -oxidation [57]. Txoj kev retinol metabolic kuj tseem raug txo qis hauv HC nyuj, nrog kev qhia qis ntawm RBP4 thiab TTR (encoding retinol-binding protein thiab transthyretin, raws li), ob qho tib si ua raws li retinol transporters hauv cov ntshav. Kev sib cuam tshuam ntawm retinol nrog PPAR teeb liab txoj hauv kev cuam tshuam rau kev hloov pauv ntawm ntau lwm cov noob caj noob ces [58]. APOA2 thiab APOC3 ua ke nrog APOH kuj yog ib feem ntawm txoj kev cholesterol metabolic. Cov roj (cholesterol) yog ib feem tseem ceeb ntawm cov plasma membrane thiab cuam tshuam rau nws lub koom haum thiab kev ua haujlwm [59,60]. Cov kev tshawb fawb tsis ntev los no tau qhia txog lub luag haujlwm tseem ceeb rau cov roj cholesterol ua ib qho tseem ceeb ntawm kev hloov pauv hauv lub cev thiab kev tiv thaiv kab mob [61].

Txoj hauv kev ntawm glycolysis / gluconeogenesis tau cuam tshuam nrog peb qhov kev txo qis ntawm DEGs hauv HC-fed nyuj (ADH1C, ALDOB, thiab PCK1). Ntawm cov no, PCK1 encodes phosphoenolpyruvate carboxykinase 1 uas ua raws li lub ntsiab lus tseem ceeb rau kev tswj hwm ntawm gluconeogenesis. Cov enzyme no, ua ke nrog GTP, catalyzes tsim phosphoenolpyruvate los ntawm oxaloacetate, nrog rau kev tso tawm carbon dioxide thiab GDP. Kev ua kom lub cev tiv thaiv kab mob / inflammatory txoj hauv kev txhawb nqa kev hloov pauv ntawm gluconeogenic genes ntawm kev hu xov tooj zoo li receptor 4 (TLR4) [62]. Qhov no tuaj yeem ua rau lub cev tiv thaiv kab mob hloov lawv cov piam thaj metabolism los ntawm oxidative phosphorylation ntawm glycolysis los tsim ob lub zog thiab cov as-ham uas xav tau rau kev loj hlob thiab kev tiv thaiv kab mob molecule [12,63]. Qhov no ua rau muaj kev xav tau ntau ntxiv rau cov piam thaj uas sib tw tiv thaiv kev xav tau ntawm lactate ntau lawm [64].

Hauv cov ntsiab lus, cov noob qhia qhov sib txawv ntawm MP nyuj ntawm HC thiab LC cov zaub mov muab pov thawj ntawm kev tiv thaiv kab mob ntau dua thiab mob hauv LC nyuj. Qhov no tau nrog los ntawm qhov tshwm sim ntau dua ntawm mastitis. Hauv qhov sib piv, cov noob encoding qee cov proteins yuav muaj txiaj ntsig zoo rau kev noj qab haus huv thiab kev xeeb tub xws li ALAS2 thiab LIF tau raug tswj hwm hauv HC nyuj. Qhov no txhawb nqa cov ntsuas metabolic ntsuas qhia tau tias muaj kev txhim kho EBAL hauv MP nyuj ntawm HC cov zaub mov, uas tej zaum yuav pab tiv thaiv lawv tiv thaiv kev loj hlob ntawm kis kab mob lossis kab mob metabolic.

3.2. Kev sib piv ntawm qhov cuam tshuam ntawm cov khoom noj siab thiab qis qis hauv cov nyuj Primiparous

Hauv qhov zoo sib xws rau MP nyuj, PP nyuj ntawm HC noj zaub mov kuj muaj DMI siab dua, txog li 4 kg / d, tab sis cov kua mis tawm tsis tau nce ntau. Tsis muaj qhov sib txawv tseem ceeb hauv kev nthuav dav ntawm cov piam thaj, NEFA, BHB, lossis IGF-1, tsuas yog urea tau siab dua ntawm cov khoom noj LC. Hauv qhov sib piv, muaj ntau qhov sib txawv ntawm leukocyte noob qhia ntawm pawg noj zaub mov ntau dua li MP nyuj, nrog 460 vs. 173 DEGs tau txheeb xyuas hauv HC thiab LC kev sib piv, ntawm 83% tau upregulated hauv PP nyuj ntawm HC noj. Tsuas yog ib feem me me ntawm DEGs sib tshooj ntawm ob pawg hnub nyoog (Daim duab 3), qhia tias kev hloov pauv hauv leukocyte muaj nuj nqi rau kev noj zaub mov thaum cev xeeb tub tau nkag siab ntau dua hauv PP nyuj dua li MP nyuj. Peb tau cia siab tias HC kev noj haus yuav muaj txiaj ntsig zoo rau PP nyuj los ntawm kev nce lawv cov DMI thiab ua kom tau raws li cov kev xav tau ntawm cov protein uas tsis muaj degradable thiab metabolizable. EBAL tau raug txhim kho tiag tiag ntawm HC noj zaub mov tab sis kev tshuaj ntsuam gene qhia pom tias muaj kev tswj hwm ntau dua ntawm cov noob koom nrog hauv kev tiv thaiv kab mob. Cov nyuj pub HC kuj muaj qhov sib piv ntau dua ntawm PMNs: UEC hauv lawv lub tsev menyuam nrog rau SCC ntau dua thiab ntau tus neeg mob mastitis. Qhov no qhia tau hais tias lawv tau ntau dua, ntau dua li tsawg dua, muaj kab mob. Peb yav dhau los pom tias cov neutrophils sau los ntawm PP nyuj nyob rau hauv txoj kev tshawb no nyob rau hauv thawj peb lub lis piam ntawm lactation muaj ntau dua phagocytic Performance index thiab oxidative burst index piv nrog cov MP nyuj, tab sis lub 2- txoj kev los ntawm kev noj haus thiab parity ntawm Cov kev ntsuas no tsis tau tshaj tawm [32].

Cov txheej txheem tiv thaiv kab mob tau txheeb xyuas hauv HC vs. LC kev sib piv suav nrog kev txhim kho ntawm cov cell nto receptor thiab cov qauv kev paub txog kev pom zoo, chemotaxis, cytokine ntau lawm, thiab leukocyte tsiv teb tsaws hauv HC-fed nyuj. Kev txheeb xyuas DEGs tau cuam tshuam nrog ntau yam kev tiv thaiv kab mob, suav nrog ntau yam tshuaj tiv thaiv kab mob peptides (AMP) (CATHL6, CXCL13, DEFB1, LTF, PGLYRP1, PGLYRP4, SA100A8, SA100A9, S100A1, thiab SLC11A1). Cov no tuaj yeem tsis tsuas yog tua cov kab mob nkag mus ncaj qha tab sis kuj pab los ntawm kev hloov pauv lwm yam kev tiv thaiv kab mob thiab tshuaj tua kab mob [65–67]. Upregulation ntawm antimicrobial peptides nyob rau hauv leukocyte transcriptomic profiles tau yav tas los tau pom nyob rau hauv nyuj nrog kev kho mob mastitis [47,68] thiab metritis / endometritis [69,70]. Lub leukocyte adhesion muaj nuj nqi yog txuam nrog 16 upregulated thiab tsib downregulated DEGs nyob rau hauv cov tsiaj noj HC. Adhesion ntawm leukocytes rau cov phab ntsa capillary yog thawj kauj ruam tseem ceeb hauv kev ua kom lawv hloov mus los ntawm cov ntshav thiab kev khiav mus rau qhov chaw ntawm cov ntaub so ntswg puas, kab mob, thiab mob [71]. Ob leeg cell-cell thiab cell-matrix kev sib cuam tshuam cuam tshuam rau leukocyte phenotype, thiab dysregulation ntawm adhesion txoj hauv kev tuaj yeem ua rau muaj kev ua kom tsis tu ncua leukocyte nrog kev kho tsis tau o [72]. Ntawm cov upregulated DEG txheeb xyuas, ADAM8, ANGPTL3, CD24, ICAM3, thiab THY1 yog tag nrho cov koom nrog extravasation [73,74] thaum FN1, NRP1, TNFAIP6, thiab VCAN muaj peev xwm ua haujlwm hauv leukocyte cell lag luam thiab ua haujlwm hauv cov ntaub so ntswg mob [72, 75] ib. Cov noob encoding cov chemokine receptors CXCR1 thiab CXCR2 kuj tau tswj hwm hauv HC-fed nyuj; Cov no yog ob qho tib si tseem ceeb hauv kev txhawb cov chemotaxis ntawm PMN mus rau qhov chaw kis kab mob nrog rau kev ua kom muaj cov txheej txheem biochemical uas tua cov kab mob invading [76].

Ntawm cov noob caj noob ces cuam tshuam nrog adhesion nyob rau hauv HC-fed nyuj, BCAR1 encodes ib tug multifunctional protein hu ua cas nrog kev koom tes nyob rau hauv cell motility, apoptosis, thiab cell voj voog tswj [77]. Polymorphisms hauv BCAR1 yav dhau los tau cuam tshuam nrog SCC thiab mastitis tsis kam [78]. ADGRG1 (tseem hu ua GPR56) encodes G protein-coupled receptor uas khi collagen 3 thiab transglutaminase 2, ob qho tib si ntawm cov ntaub so ntswg stroma. ADGRG1 tau pom tias ua lub luag haujlwm hauv tib neeg lub cev tua neeg (NK) hlwb, uas nws inhibits lawv cytotoxicity [79]. Nws tus kheej qhia yog downregulated tom qab cytokine-induced activation, uas yuav ua raws li cov txiaj ntsig tau qhia ntawm no. CD96 protein kuj ua raws li qhov inhibitory checkpoint receptor ntawm NK hlwb [80]. Cov kev tshawb fawb yav dhau los ntawm kev hloov pauv hauv leukocyte transcriptome thaum lub sijhawm hloov pauv kuj tseem pom cov kev hloov pauv hauv cov noob qhia txog kev hloov pauv hloov pauv txawm hais tias muaj qhov sib txawv, qhia txog kev ua kom muaj zog tom qab calving [81] lossis inhibition [82], ntsig txog. Peb qhov kev tsom xam kuj tau txheeb xyuas ntau qhov sib txawv ntawm cov amino acid metabolism hauv kev kos npe rau txoj hauv kev hauv PP nyuj ntawm HC noj zaub mov piv nrog cov LC noj zaub mov, cuam tshuam nrog enzymes encoded los ntawm tsib upregulated DEGs (ARG2, ASS1, GPT2, SDS, thiab SDSL) . Ntawm cov no, ASS1 encodes arginine succinate synthase 1, uas catalyzes cov kauj ruam kawg ntawm arginine biosynthetic txoj kev, thaum ARG2 encodes arginase, catalyzing hydrolysis ntawm arginine rau ornithine thiab urea. L-arginine kuj tseem tuaj yeem hloov mus rau nitric oxide, lub teeb liab molecule uas ua lub luag haujlwm tseem ceeb hauv cov kab mob ntawm qhov mob [83]. Glutamic-pyruvic transaminase 2 (GPT2) yog mitochondrial enzyme uas catalyzes reversible transamination ntawm alanine thiab 2-oxoglutarate los tsim pyruvate thiab glutamate. Cov noob no tau hloov kho nyob rau hauv cov xwm txheej ntawm metabolic kev ntxhov siab thiab ua lub luag haujlwm hauv kev tsav cov gluconeogenesis los ntawm cov amino acid metabolism [84]. Serine dehydratase (SDS) encodes ib qho enzyme uas hloov L-serine rau pyruvate thiab ammonia, thaum serine dehydratase (SDSL) tau kwv yees tias yuav koom nrog txoj hauv kev ntawm isoleucine biosynthesis los ntawm threonine.

Txoj hauv kev ntawm cov roj cholesterol metabolism tau cuam tshuam nrog plaub qhov kev tswj hwm DEGs ntawm HC noj zaub mov (ANGPTL3, LRP1, SCARB1, thiab SORT1). Qhov no tuaj yeem ua rau muaj cov roj cholesterol ntau hauv cov leukocytes ntawm HC-nyiam nyuj thiab txhawb kev mob, nrog rau kev nthuav tawm ntawm TLR signaling, inflammasome activation, thiab ntau dua ntawm monocytes thiab neutrophils nyob rau hauv cov pob txha pob txha thiab spleen [85]. Txoj kev ntawm arachidonic acid metabolism nrog tsib upregulated DEGs (raws li teev yav dhau los) ua rau zus tau tej cov cascades ntawm pro- thiab anti-inflammatory khoom, xws li prostaglandins thiab leukotrienes [86]. Txoj kev glycerollipid metabolism tau cuam tshuam nrog plaub qhov kev tswj hwm DEGs (DGAT2, DGKG, GK, thiab GPAT3) uas encode rau lipogenic noob koom nrog hauv kev sib txuas ntawm triacylglycerol. Nws tsub zuj zuj tuaj yeem ua rau cov leukocyte activation thiab o [87,88]. Tag nrho cov kev tshawb pom no txhawb qhov kev txiav txim siab tias HC kev noj haus tau tswj hwm leukocyte metabolic txoj hauv kev hauv PP nyuj nyob rau hauv ib txoj kev uas ua rau lawv lub cev tiv thaiv kab mob / inflammatory teb. Kev ua haujlwm yav dhau los hauv nyuj tau tsom mus rau lub sijhawm qhuav thiab tau pom tias kev noj zaub mov ntau dhau thiab BCS siab nyob rau lub sijhawm no txhawb nqa cov lipid mobilization tom qab thiab muaj kev cuam tshuam ntau ntxiv thaum lub sijhawm peripartum [34]. Hauv kev tshawb fawb tam sim no, uterine PMN: UEC piv thiab qhov sib txawv ntawm SCC siab dua txhawb cov lus qhia tias muaj cov leukocyte ntau ntxiv mus rau lub tsev menyuam thiab cov qog mammary hauv PP nyuj tau txais HC noj. Txawm hais tias qhov no yog ib qho tseem ceeb ntawm kev tiv thaiv kab mob, overactivation tuaj yeem ua rau hyper-o. Kev kawm ntxiv nrog rau tus qauv loj dua yuav tsum tau ua kom paub tseeb tias cov kev tshawb pom no.

3.3. Zoo sib xws hauv Teb rau Kev Noj Qab Haus Huv los ntawm Multiparous thiab Primiparous Nyuj

In terms of metabolic changes, both the MP and PP cows had higher circulating concentrations of urea when on the LC diet. Blood urea in both late pregnancy and early lactation may rise following mobilization of amino acids stored in skeletal muscle [89] or when dietary protein supply exceeds energy availability or protein needed [90], so these situations could have applied here. Elevated levels of urea have been associated with reduced fertility, but only at >4.5 mmol / L, siab dua cov concentrations uas tau mus txog hauv cov tsiaj noj LC hauv txoj kev tshawb no [91]. Hais txog cov ntaub ntawv leukocyte gene transcription, nws yog qhov nthuav kom nco ntsoov tias DEGs muab los ntawm HC thiab LC kev sib piv hauv ob pawg hnub nyoog tau txhawb nqa txoj hauv kev ntawm cov protein zom thiab nqus, uas cov noob encoding ntau yam isoforms ntawm collagen ua lub luag haujlwm tseem ceeb. . Ntawm lawv, muaj peb lub noob caj noob ces collagen (COL1A1, COL1A2, thiab COL3A1) hauv MP thiab PP nyuj, thiab ib qho downregulated (COL5A3) collagen noob hauv MP nyuj. Lawv qhov kev qhia qhov tseem ceeb hauv cov qauv me me, tab sis qhov sib txawv tseem ceeb. Ib feem ntawm cov RNA no tuaj yeem yog los ntawm fibrocytes, cov neeg nyob hauv cell uas muaj tsuas yog 0.1–{14}}.5% ntawm cov cell nonerythrocytic hauv cov ntshav peripheral [92,93]. Collagen yog ib qho kev tiv thaiv kab mob ntev ntev uas cuam tshuam nrog ntau yam kev tiv thaiv kab mob / kab mob [93,94]. Nws upregulated ntau lawm nyob rau hauv circulating ntshav los ntawm HC noj zaub mov tej zaum yuav muaj feem xyuam rau leukocyte muaj nuj nqi.

3.4. Qhov cuam tshuam rau Fertility

Ntau cov kev tshawb fawb yav dhau los tau tshaj tawm tias kev sib txuas ntawm cov metabolism hauv thiab kev tiv thaiv kab mob thiab kab mob ntawm cov nyuj thaum lactation thaum ntxov muaj kev cuam tshuam loj rau lawv cov fertility tom qab (xws li, [38,95]). Peb tus kheej ua haujlwm tau pom tias MP nyuj nrog qis IGF -1 concentration ntawm 14 DIM tsis tshua muaj xeeb tub ntawm tag nrho [37]. Tsis ntev los no, peb tau tshaj tawm tias 63% ntawm cov nyuj uas qis IGF-1 nyob rau lub sijhawm no tau ntsib ntau dua ib qho teeb meem kev noj qab haus huv thaum lawv thawj 35 DIM piv nrog tsuas yog 26% ntawm IGF siab -1 nyuj. Qhov no suav nrog ntau tus tsiaj uas muaj kab mob hauv tsev menyuam thiab kev kho mob mastitis [10]. Foley et al. [69] sib txawv ntawm cov nyuj noj qab nyob zoo, uas muaj peev xwm kho tau homeostasis li ntawm 3 lub lis piam tom qab calving, thiab lwm tus uas tau ntsib ib tug mob hnyav thiab ntev inflammatory teb uas tom qab ntawd mus rau kev kho mob endometritis. Kev koom tes nrog cov ntshav peripheral tau pom los ntawm Galvão li al. [96] uas tau pom tias cov neutrophils los ntawm nyuj nyob rau hauv EBAL tsis zoo muaj cov ntsiab lus glycogen qis dua ntawm xya DIM thiab cov tsiaj no tau ntsib cov kab mob uterine ntau dua, uas cuam tshuam nrog kev txo qis ntawm cov roj oxidative rau kev tiv thaiv kab mob. Clinical mastitis nyob rau hauv thaum ntxov lactation kuj yog txuam nrog nce tus nqi ntawm pre-implantation embryo poob, nrog ib co qhia tias ib tug tsawg BCS ntxiv tsub kom qhov kev pheej hmoo [97]. Ib tug xov tooj ntawm cov txheej txheem txuam nrog cytokine thiab prostaglandin ntau lawm thiab lwm yam inflammatory mediators tau pom tias yuav cuam tshuam rau lub zes qe menyuam thiab / los yog ua rau ib tug tsis zoo uterine ib puag ncig [98,99]. Cov ntaub ntawv fertility tau los ntawm cov nyuj hauv peb txoj kev tshawb fawb tau txhawb nqa qhov kev tshawb pom ntsig txog lawv lub cev tiv thaiv kab mob thiab kev noj qab haus huv hauv kev lactation thaum ntxov. MP nyuj ntawm LC noj zaub mov yuav tsum muaj ntau S / C raws li lawv cov neeg pluag EBAL ua ke nrog cov pov thawj los ntawm kev soj ntsuam ntawm cov leucocyte transcriptome ntawm ntau zog tiv thaiv kab mob nyob rau hauv kev kawm, raws li kev txhawb nqa los ntawm lawv cov mob ntau dua ntawm mastitis. Hauv qhov sib piv, PP nyuj ntawm HC noj zaub mov tau siv sijhawm ntev dua los xeeb tub thiab tsawg dua cev xeeb tub hauv kev sib piv nrog LC-feed nyuj. Lawv muaj pov thawj ntau dua ntawm kev mob thaum cev xeeb tub thaum ntxov txawm tias lawv suav EBAL zoo dua. Tam sim no, cov txheej txheem hauv qab uas ua rau lawv cov kev noj qab haus huv tsis zoo thiab kev xeeb tub tsis paub tseeb txawm hais tias peb kuj tau pom cov pov thawj raws li lub ntiaj teb cov noob qhia txog kev nce siab hauv siab thiab fibrosis (Cheng, Me, Ferris, Takeda, Ingvartsen, Crowe thiab Wathes, kev soj ntsuam tsis tau tshaj tawm) .

3.5. Kev txwv ntawm Kev Kawm

Muaj tsawg dua PP nyuj rau ib pab pawg, thiab qhov no txo qis lub zog ntawm kev txheeb xyuas ntawm cov phenotypes. Kev kawm ntxiv nrog rau cov qauv loj dua yog li ntawd yuav tsum tau lees paub qhov kev noj zaub mov muaj txiaj ntsig ntawm kev yug me nyuam thiab kab mob. Hauv kev tshawb fawb tam sim no, peb tau rho tawm tag nrho RNA los ntawm tag nrho cov ntshav peripheral siv Tempus hlab thiab nws qhov kev cais tawm. Qhov no muab kev yooj yim ntawm kev sau qoob loo rau kev kawm ua liaj ua teb loj tab sis tsis cais cov cell hom, uas yuav suav nrog T thiab B lymphocytes, ntuj killer cells, platelets, monocytes, granulocytes (neutrophils, eosinophils, thiab, basophils), thiab fibrocytes. Cov ntaub ntawv qhia txog cov noob tau nthuav tawm yog li ntawd tau cuam tshuam los ntawm kev kho mob tshwm sim ntawm cov txheeb ze ntawm cov cell tshwj xeeb ntxiv rau lawv cov kev hloov pauv ntawm tus kheej. Cov txiaj ntsig no kuj yog raws li qib kev hloov pauv cov noob caj noob ces thiab tsis suav nrog cov ntaub ntawv ntawm lawv cov txheej txheem tom qab kev txhais lus, uas tseem yuav cuam tshuam ntau npaum li cas cov protein tsim tawm.

4. Cov ntaub ntawv thiab cov txheej txheem

4.1. Tsiaj txhu thiab khoom noj

Tag nrho cov txheej txheem tau ua raws li Txoj Cai Tsiaj (Kev Tshawb Fawb) Txoj Cai 1986 thiab them los ntawm Lub Tsev Haujlwm Lub Tsev Haujlwm Daim Ntawv Tso Cai Tus lej PPL2754 thiab Daim Ntawv Pov Thawj ntawm Kev Tsim Kho. Txoj haujlwm tseem raug pom zoo los ntawm Pawg Saib Xyuas Kev Ncaj Ncees thiab Kev Noj Qab Haus Huv ntawm Agri-Food thiab Biosciences Institute (AFBI, Belfast, Northern Ireland, UK). Rau caum-ob Holstein-Friesian mis nyuj nyuj tau nrhiav los ntawm AFBI pab tsiaj. Ntawm lawv, 18 yog PP (lactation 1) thiab 44 MP nrog lactation naj npawb 2–7 (3.5 ± 1.28) thiab txhua tus nyuj tau noj qab nyob zoo raws li kws kho tsiaj kuaj. Lub cev hnyav yog 680 ± 62 (Mean ± STD) kg rau MP nyuj thiab 550 ± 39 kg rau PP nyuj. Tom qab calving, PP thiab MP nyuj raug cais rau peb pawg noj zaub mov, nrog rau kev faib nyob rau hauv txhua pab pawg hnub nyoog sib npaug rau kev kwv yees kis tau rau cov rog ntxiv rau cov protein (kg), pre-calving BW, thiab BCS. MP nyuj kuj tau sib npaug rau qhov sib luag thiab lactation yav dhau los 305-hnub mis nyuj tawm los. Cov nyuj tau muab los ntawm (1) tsis tshua muaj siab (LC, 30% concentrate ntxiv rau 70% nyom silage, n=6 rau PP thiab n=14 rau MP); (2) nruab nrab concentrate (MC, 50% concentrate ntxiv 50% nyom silage, n=6 rau PP thiab n=15 rau MP) lossis (3) siab concentration (HC, 70% concentrate ntxiv 30% nyom silage, n=6 rau PP thiab n=15 rau MP) cov zaub mov (feem pua ntawm cov teeb meem qhuav). Cov concentrated rau txhua qhov kev kho mob tau tsim los ua kom tiav tag nrho cov khoom noj khoom haus crude protein (CP) concentration rau txhua tus ntawm LC, MC, thiab HC (152, 152, thiab 154 g / kg DM feem), thaum suav tag nrho cov khoom noj metabolizable zog ( ME) cov ntsiab lus yog 12.0, 12.4 thiab 12.8 MJ / kg DM. Cov khoom noj tau kwv yees muab 1556, 1997, thiab 2420 g / d zoo rumen degradable protein; 559, 733, thiab 888 g / d noj zaub mov tsis muaj protein ntau thiab 1346, 1817, thiab 2275 g / d metabolizable protein rau LC, MC thiab HC, raws li. Kev nkag mus rau kev kho mob tau tswj hwm los ntawm Calan Broadbent feeding system (American Calan Inc., Northwood, NH, USA) txuas mus rau ib qho kev txheeb xyuas hluav taws xob, uas tso cai rau tus neeg noj nyuj noj txhua hnub. Kev noj zaub mov rau txhua qhov kev kho mob tau muab rau ntawm 107% ntawm cov hnub dhau los 'kev noj haus kom ntseeg tau libitum noj. Txhua tus nyuj kuj tau muab ntxiv 0.5 kg mloog zoo ntawm txhua qhov kev pub mis nyuj los ntawm kev pub mis hauv tsev los pab tswj cov nyuj zoo. Txoj kev tshawb fawb tam sim no yog ib feem ntawm txoj haujlwm dav dua thiab tag nrho cov ntsiab lus ntawm cov khoom noj muaj, kev tswj kev noj zaub mov, thiab cov khoom noj khoom haus tau piav qhia yav dhau los [32].

4.2. Nyuj Phenotype Data Collection

Lub cev hnyav tau sau ob zaug ib lub lim tiam uas siv cov ntsuas ntsuas. BCS tau kwv yees nyob ib ncig ntawm 14 DIM [100]. Txhua tus nyuj tau mis nyuj ob zaug ib hnub thiab lawv cov txiaj ntsig txhua hnub tau sau tseg. Cov mis nyuj kuaj tau raug tshuaj xyuas ob zaug ib lub lim tiam siv cov kev ntsuam xyuas nruab nrab ntawm qhov ntsuas ntawm cov protein, rog, thiab lactose, thiab cov mis somatic hlwb raug suav. Ntxiv cov kua mis thaum sawv ntxov (2 × 8 mL) tau sau ob zaug hauv ib lub lim tiam thiab khaws cia ntawm −18 ◦C rau kev soj ntsuam ntawm LDH (EC. 1.1.1.27) thiab NAGase (EC 3.2.1.30) siv fluorometric assays [101]. Lub zog kho cov kua mis tawm (ECM; kg / hnub) raug xam raws li cov kev siv hauv peb pab pawg [32]. EBAL ntawm txhua tus nyuj tau kwv yees siv txoj kev tau piav qhia yav dhau los [102].

Clinical mastitis tau kuaj pom siv cov txheej txheem raws li kev soj ntsuam txhua hnub rau kev hloov pauv ntawm cov mis nyuj (piv txwv li, flakes, clots), zoo, mis nyuj tawm los, thiab mammary inflammatory teb (redness, o, kub, los yog mob). Mis SCC nyeem ua ke nrog cov kev kuaj mob tau siv los faib cov nyuj ua peb pawg. Cov nyuj noj qab nyob zoo tau raug txhais tias muaj SCC <100,{1}} hlwb/mL mis nyuj thiab tsis muaj tsos mob tshwm sim. Subclinically mastitic nyuj tau txhais tias muaj SCC ntawm 100, 000 thiab 400, 000 hlwb/mL mis nyuj thiab tsis muaj tsos mob tshwm sim. Cov nyuj tau kuaj pom tias muaj mob mastitis muaj SCC> 400,000 cell/mL mis nyuj thiab pom qee cov tsos mob saum toj no. nyuj tau inseminated ntawm pom estrus siv ib txwm herd xyaum thiab fertility cov ntaub ntawv rau lub sij hawm ntawm lub tom ntej lactation los yog kom txog thaum tus tsiaj raug culled tau muab los ntawm herd cov ntaub ntawv. Cov ntaub ntawv tau tshaj tawm suav nrog hnub rau thawj qhov kev pabcuam (DFS), hnub rau kev xeeb tub (hnub qhib), cov kev pabcuam ib lub tswvyim, thiab feem ntau ntawm cov nyuj uas xeeb menyuam. Tsis tas li ntawd, cov ntaub ntawv xav tau tau qhab nia siv 4-point hauv calf los ntawm (ICB) qhab nia raws li (1)<100 days, (2) 100–200 days, (3) >200 hnub, los yog (4) ua tsis tau tejyam xeeb los yog culled.

4.3. Uterine Cytology Analysis

Ib tus qauv cytobrush uterine (Minitube, Minitüb GmbH, Tiefenbach, Lub teb chaws Yelemees) raug coj los ntawm txhua tus nyuj nyob ib ncig ntawm 14 DIM los ntsuas endometrial cytology, raws li tau piav qhia yav dhau los [103]. Ib tug ob-tiv thaiv cytobrush tau coj manually los ntawm lub ncauj tsev menyuam mus rau hauv lub tsev menyuam, tus neeg saib xyuas sab hauv yog extruded los ntawm tus neeg saib xyuas sab nrauv, thiab txhuam tau tig maj mam tawm tsam phab ntsa endometrial. Tom qab ntawd tus txhuam tau muab tshem tawm mus rau hauv tus neeg saib xyuas sab hauv thiab tshem tawm. Slides rau kev ntsuam xyuas cytological tau npaj los ntawm dov lub cytobrush mus rau lub iav tsom iav kom huv si thiab kho cov qauv nrog Fisherbrand™ CytoPrep™ Cytology Fixative (Fishers Scientific, Blanchardstown, Ireland). Tsau swb raug xa mus rau UCD Lub Tsev Kawm Ntawv ntawm Veterinary Medicine, University College Dublin, Ireland rau kev ua thiab stained nrog hloov kho Giemsa stain. Kev ntsuam xyuas cytological tau ua los ntawm kev suav PMNs UECs ntawm 400 × magnification (Leitz Labourlux-S, Wetzlar, Lub teb chaws Yelemees) thiab txiav txim siab lawv qhov piv, qhov nruab nrab suav ntawm 10 lub zog loj hauv ib qho swb.

4.4. Kev soj ntsuam ntawm Circulating Metabolites thiab IGF-1

Ntawm 14 ± 2 (txhais tau tias ± STD) hnub tom qab calving, 10 mL ntawm cov ntshav kuaj tau sau los ntawm cov hlab ntsha jugular ntawm tag nrho cov nyuj mus rau hauv Na heparin hlab rau cov ntshav plasma thiab cov hlab ntsha. Tom qab kev sib cais ntawm cov ntshav los yog cov ntshav nrog centrifugation, lawv tau khaws cia ntawm −20 ◦C kom txog thaum kev soj ntsuam. Cov concentration ntawm plasma qabzib, urea, BHB, NEFA, thiab cov roj cholesterol raug ntsuas los ntawm cov txheej txheem tau piav qhia yav dhau los [20,25]. Luv luv, ntshav NEFA concentration tau txiav txim siab nrog ACS-ACOD txoj kev siv NEFA C Cov Khoom Siv (Wako, Neuss, Lub Tebchaws Yelemees). Plasma glucose tau suav nrog ib txoj kev enzymatic (ADVIA 1800 Clinical Chemistry System, Siemens Healthcare Diagnostics, Ballerup, Denmark). Serum BHB tau txiav txim siab los ntawm kev ntsuas qhov nqus ntawm 340 nm vim kev tsim cov NADH ntawm alkaline pH nyob rau hauv muaj BHB dehydrogenase. Serum urea tau txheeb xyuas los ntawm spectrophotometric. Intra- thiab inter-assay coefficients ntawm variation (CV) nyob rau hauv txhua rooj plaub hauv qab peb thiab plaub feem pua, feem, rau ob qho tib si qis thiab siab tswj cov qauv. Concentrations ntawm serum IGF{11}} tau suav nrog radioimmunoassay tom qab cov kua qaub ethanol rho tawm [104]. Intra-assay CV yog 12.4, 7.5, thiab 9.9% rau cov qauv qis, nruab nrab, thiab siab tswj, feem.

4.5. Ntshav RNA Extraction

Cov ntshav kuaj rau RNA rho tawm tau sau los ntawm jugular venepuncture los ntawm txhua tus nyuj ntawm 14 ± 2 DIM rau hauv Tempus ntshav RNA hlab (Thermo-Fisher Scientific, Loughborough, UK). Cov raj tau shaken rau 15–20 sec tam sim ntawd thaum sau, ces khov thiab khaws cia ntawm −80 ◦C rau RNA rho tawm. Tag nrho cov ntshav RNA tau muab rho tawm siv Tempus Spin RNA cais cov khoom siv (Thermo-Fisher) ua raws li cov chaw tsim khoom cov lus qhia raws li tau piav qhia yav dhau los [20]. Agilent BioAnalyzer 2000 (Agilent Technologies UK Ltd., Cheadle, UK) nrog Agilent RNA 6000 Nano Kit (Agilent Technologies UK Ltd., Cheadle, UK) tau siv los ntsuas RNA kom muaj nuj nqis thiab kev ncaj ncees. Tsis tas li ntawd, qhov ntau thiab purity tau raug lees paub nrog NanoDrop 1000 (Thermo Fischer). Cov ntaub ntawv zoo tau sau tseg hauv Cov Ntaub Ntawv Ntxiv S3. Qhov no tau pom tias tag nrho cov qauv RNA muaj kev ncaj ncees (RIN tooj> 8.7, 9.3 ± 0.3) thiab purity (260/280 ntawm 2.01 thiab 2.15, txhais tau tias ± STD 2.10 ± 0.03), yog li tsis muaj tsiaj raug tshem tawm ntawm kev tshuaj ntsuam. RNA tau khaws cia ntawm −80 ◦C rau RNA sequencing tom ntej.

4.6. RNA-Sequencing, Mapping thiab Quantification

Cov rho tawm leukocyte RNA tau ua raws li ntawm Illumina NextSeq 500 platform raws li tau piav qhia yav dhau los [68]. Luv luv, siv epMotion kua tuav chaw ua haujlwm (Eppendorf, Hamburg, Lub Tebchaws Yelemees) 750 ng tag nrho RNA tau thim rov qab mus rau cDNA cov tsev qiv ntawv sib txuas nrog Illumina TruSeq Stranded Total RNA Library Prep Ribo-Zero Gold kit (Illumina, San Diego, CA, USA, USA ). Cov tsev qiv ntawv cDNA tau sib sau ua ke ntawm Illumina NextSeq 500 sequencer ntawm 75 nucleotide ntev ib-kawg nyeem kom ncav cuag qhov nruab nrab ntawm 33.5 lab nyeem ib tus qauv. Cov ntaub ntawv FASTQ nyoos tau muab tso rau European Nucleotide Archive (E-MTAB-9347 thiab E-MTAB-9431). Txhua qhov kev soj ntsuam ua ke tau ua tiav siv CLC Genomic Workbench v21 (Qiagen, Manchester, UK). Txhua tus qauv muaj cov ntawv nyeem los ntawm plaub txoj kab, thiab lawv tau muab tso rau hauv ib daim ntawv fastq. Qhov zoo ntawm ob qho tib si raw thiab trimmed fastq cov ntaub ntawv tau soj ntsuam tom qab Illumina Pipeline 1.8 thiab cov ntawv nyeem tsis tau raug tshem tawm. Cov ntawv nyeem tom qab ntawd tau kos npe rau qhov kev siv genome Bos taurus los ua ke (ARS-UCD1.2 muab los ntawm RefSeq ntawm https://www. ncbi.nlm.nih.gov/assembly, nkag mus rau 1 Lub Ib Hlis 2021) thiab suav raws li nyeem ib lub noob, nyeem ib kilobase lab (RPKM), thiab transcripts per kilobase lab (TPM). Cov no tau muab khaws cia ua cov ntaub ntawv gene qhia (GE) hauv CLC Genomics Workbench los siv rau kev soj ntsuam hauv qab no ntawm kev qhia cov noob sib txawv.

4.7. Kev soj ntsuam ntawm qhov sib txawv ntawm Gene Expression ntawm Pawg Kev Noj Qab Haus Huv

Ua ntej qhov kev ntsuam xyuas qhov sib txawv rau kev noj zaub mov zoo, peb tau siv qhov kev tshuaj ntsuam xyuas tseem ceeb (PCA) nrog rau RPKM qhov tseem ceeb los txheeb xyuas cov neeg sab nrauv, thiab qhov no qhia tau tias ob tug nyuj (ntshav020009, MP thiab Blood020103, PP) yog cov pejxeem outliers thiab yog li ntawd raug tshem tawm los ntawm kev tshuaj xyuas ntxiv (Cov Ntaub Ntawv Ntxiv S4A). Thawj qhov kev tshuaj ntsuam xyuas tseem pom tau tias tsuas muaj kev sib tshooj ntawm cov noob caj noob ces tag nrho ntawm PP thiab MP nyuj (Cov Ntaub Ntawv Ntxiv S2B). Qhov no txhawb cov qauv kev tshawb fawb thawj zaug los tshuaj xyuas txhua pawg hnub nyoog sib cais. Cov ntaub ntawv GE tau muab los ntawm tag nrho cov qauv ntawm tus kheej yog li cais los ntawm pawg hnub nyoog (PP, n=5–6 ib pab pawg thiab MP, n=14–15 rau ib pab). Cov DEGs ntawm pawg noj zaub mov hauv PP lossis MP nyuj tau txheeb xyuas nrog CLC Genomics Workbench V21 ntawm txoj kev ANOVA-zoo li ib txoj kev. Qhov kev tshawb pom cuav (FDR) rau ntau qhov kev ntsuam xyuas tau hloov kho nrog Benjamini-Hochberg (BH) thiab qhov tseem ceeb tau txiav txim siab ntawm p <0.05. Cov kev hloov pauv (FCs) raug xam raws li cov noob qhia piv ntawm cov concentration siab dua rau pawg qis concentrate (piv txwv li, HC vs. LC, MC vs. LC, lossis HC vs. MC) yog tias tus nqi ntawm pawg concentration siab dua. tau ntau dua li ntawm pawg qis concentrate (zoo fold hloov, upregulation). Yog hais tias tus nqi ntawm pawg qis concentrate yog ntau dua li ntawm cov concentration siab dua, qhov piv ntawm cov concentration qis dua rau cov concentration siab dua tau siv (piv txwv li, LC vs. HC, MC vs. HC, thiab LC vs. MC. ) (tsis zoo fold hloov, downregulation). Lub DEGs upregulated thiab downregulated nrog ib tug kiag li fold hloov loj dua los yog sib npaug rau 1.5 ntawm cov pab pawg neeg noj zaub mov raug xaiv los soj ntsuam ntxiv.

4.8. Gene Ontology (GO) Enrichment Analysis

Cov DEGs tau muab los ntawm kev sib piv ntawm cov pab pawg noj zaub mov tau muab tso rau hauv Partek Genomics Suite V7.1 (Partek Incorporation, Chesterfield, MO, USA) rau GO enrichment tsom xam rau kev tshawb nrhiav txog kev ua haujlwm lom neeg thiab kev sib cuam tshuam ntawm DEGs thiab cov koom nrog Kyoto Encyclopedia ntawm Genes thiab Genomes (KEGG) txoj hauv kev nrog genome ntawm Bos taurus ARS-UCD1.2. Fisher qhov tseeb qhov kev sim nrog BH hloov kho tau siv thiab qhov tseem ceeb ntawm cov ntaub ntawv tau txiav txim siab ntawm p < 0.05.

4.9. Kev txheeb xyuas cov ntaub ntawv Phenotype

Cov ntaub ntawv muab los ntawm txhua tus nyuj yog thawj zaug faib los ntawm pawg hnub nyoog (PP thiab MP nyuj), raws li kev tshawb fawb tsim. Qhov tseem ceeb ntawm DMI, BW, mis tsis, EBAL, BCS, circulating metabolites (glucose, urea, BHB, NEFAs, cholesterol, thiab IGF{{0}}), SCC (logarithmically transformed), thiab uterine cell suav. thiab lawv cov piv txwv tau sau tseg raws li qhov txhais tau tias ± tus qauv yuam kev ntawm qhov nruab nrab (SE). Kev txheeb xyuas kev txheeb xyuas tau siv los sib piv qhov sib txawv ntawm pawg neeg noj zaub mov uas siv ib txoj kev ANOVA ua rau hauv SPSS V28 software pob (Chicago, IL, USA). Qhov sib txawv ntawm qhov sib txawv rau txhua qhov sib txawv tau sim nrog Levene cov txheeb cais ua ntej ANOVA. Cov txiaj ntsig tau pom tias kev sib koom ua ke ntawm pawg rau ECM, EBAL, qabzib, urea, BHB, thiab IGF-1 hauv PP nyuj tsis tau ua tiav, yog li kev hloov logarithmic tau siv rau cov hloov pauv no. Qhov twg ANOVA qhia qhov tseem ceeb, ntau qhov kev sib piv nrog Fisher's LSD txoj kev tau ua los txheeb xyuas qhov sib txawv. Raws li homogeneity ntawm qhov sib txawv rau cov ntaub ntawv ntawm mis nyuj SCC thiab uterine cytology tsis tuaj yeem ua tiav tom qab kev hloov pauv ntawm logarithmic, cov kev hloov pauv no tau sim siv Kruskal-Wallis ib-txoj kev ANOVA nrog Dunn ntau qhov sib piv. Cov ntaub ntawv fertility tau sim nrog txoj kev Wilcoxon. Nyob rau hauv txhua rooj plaub, qhov tseem ceeb tau txiav txim siab ntawm p <0.05.

5. Cov lus xaus

Txoj kev tshawb no txhawb nqa kev ua haujlwm dhau los hauv kev ua kom pom tseeb kev sib txuas ntawm cov txheej txheem metabolic ntawm nyuj thaum lactation thaum ntxov thiab lawv lub cev tiv thaiv kab mob. Feem ntau cov kev tshawb fawb yav dhau los tsom rau kev txhim kho kev noj qab haus huv tom qab yug me nyuam los ntawm kev noj zaub mov zoo dua tau tsom mus rau lub sijhawm ua ntej thiab pom tau tias kev noj zaub mov ntau dhau thiab BCS siab nyob rau lub sijhawm no txhawb nqa cov lipid mobilization tom qab thiab cov lus teb nce ntxiv thaum lub sijhawm peripartum [34]. Peb tau hloov pauv kev ntsuas seb nws puas tuaj yeem hloov kho lub cev tiv thaiv kab mob tom qab calving los ntawm kev hloov cov zaub mov lactation. Peb pom tau hais tias cov lus teb rau kev tsom xam ntxiv, uas tau muab cov zaub mov tsim kom tau raws li tus tsiaj lub zog thiab cov protein ntau, ua rau muaj kev sib txawv ntawm leukocyte transcriptome hauv MP thiab PP nyuj. Hauv MP nyuj, HC noj zaub mov kom meej meej tau txais txiaj ntsig zoo, vim tias cov leucocytes ntawm LC nyuj muaj kev tswj hwm ntawm kev sib ntxiv thiab coagulation cascade thiab lub cev tiv thaiv kab mob tiv thaiv kab mob. Hauv qhov sib piv, cov leukocytes hauv PP nyuj ntawm HC noj zaub mov tau pom ntau dua kev tiv thaiv kab mob / cov lus teb thiab lawv muaj PMN ntau dua: UEC piv, qhia txog kev nce leukocyte mus rau lub tsev menyuam. Cov nyuj no tom qab ntawd muaj lub sijhawm ntev ntawm calving mus rau conception, qhia tias pluag fertility. Kev ua hauj lwm ntxiv nrog cov nyuj ntau dua yog lav kom paub meej tias qhov kev tshawb pom ntawm kev noj zaub mov muaj txiaj ntsig rau kev xeeb tub thiab kom nkag siab ntau ntxiv tias cov lus teb metabolic ntawm cov khoom noj tom qab yug me nyuam txawv li cas ntawm cov tsiaj hluas.

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