Background Exposure to bisphenol A(BPA),an environmental pollutant known for its endocrine-disrupting properties,during gestation has been reported to increase the risk of fetal growth restriction(FGR)in an ovine mode...Background Exposure to bisphenol A(BPA),an environmental pollutant known for its endocrine-disrupting properties,during gestation has been reported to increase the risk of fetal growth restriction(FGR)in an ovine model of pregnancy.We hypothesized that the FGR results from the BPA-induced insufficiency and barrier dysfunction of the placenta,oxidative stress,inflammatory responses,autophagy and endoplasmic reticulum stress(ERS).However,precise mechanisms underlying the BPA-induced placental dysfunction,and subsequently,FGR,as well as the potential involvement of placental ERS in these complications,remain to be investigated.Methods In vivo experiment,16 twin-pregnant(from d 40 to 130 of gestation)Hu ewes were randomly distributed into two groups(8 ewes each).One group served as a control and received corn oil once a day,whereas the other group received BPA(5 mg/kg/d as a subcutaneous injection).In vitro study,ovine trophoblast cells(OTCs)were exposed to 4 treatments,6 replicates each.The OTCs were treated with 400μmol/L BPA,400μmol/L BPA+0.5μg/m L tunicamycin(Tm;ERS activator),400μmol/L BPA+1μmol/L 4-phenyl butyric acid(4-PBA;ERS antagonist)and DMEM/F12 complete medium(control),for 24 h.Results In vivo experiments,pregnant Hu ewes receiving the BPA from 40 to 130 days of pregnancy experienced a decrease in placental efficiency,progesterone(P4)level and fetal weight,and an increase in placental estrogen(E2)level,together with barrier dysfunctions,OS,inflammatory responses,autophagy and ERS in type A cotyledons.In vitro experiment,the OTCs exposed to BPA for 24 h showed an increase in the E2 level and related protein and gene expressions of autophagy,ERS,pro-apoptosis and inflammatory response,and a decrease in the P4 level and the related protein and gene expressions of antioxidant,anti-apoptosis and barrier function.Moreover,treating the OTCs with Tm aggravated BPA-induced dysfunction of barrier and endocrine(the increased E2 level and decreased P4 level),OS,inflammatory responses,autophagy,and ERS.However,treating the OTCs with 4-PBA reversed the counteracted effects of Tm mentioned above.Conclusions In general,the results reveal that BPA exposure can cause ERS in the ovine placenta and OTCs,and ERS induction might aggravate BPA-induced dysfunction of the placental barrier and endocrine,OS,inflammatory responses,and autophagy.These data offer novel mechanistic insights into whether ERS is involved in BPA-mediated placental dysfunction and fetal development.展开更多
Background: Enhancing the post-ruminal supply of arginine(Arg), a semi-essential amino acid(AA), elicits positive effects on milk production. Our objective was to determine the effects of Arg infusion on milk producti...Background: Enhancing the post-ruminal supply of arginine(Arg), a semi-essential amino acid(AA), elicits positive effects on milk production. Our objective was to determine the effects of Arg infusion on milk production parameters and aspects of nitrogen(N) absorption and utilization in lactating dairy cows. Six lactating Chinese Holstein cows of similar body weight(508 ± 14 kg), body condition score(3.0 ± 0), parity(4.0 ± 0), milk yield(30.6 ±1.8 kg) and days in milk(20 ± 2 d) were randomly assigned to 3 treatments in a replicated 3 × 3 Latin square design with 21 d for each period(1 week for infusion and 2 weeks for washout). Treatments were 1) Control: saline;2) Arg group: saline + 9.42 g/L L-Arg;3) Alanine(Ala) group: saline + 19.31 g/L L-Ala(iso-nitrogenous to the Arg group). Milk production and composition, dry matter intake, apparent absorption of N, profiles of amino acids(AA) in blood,urea N in urine, milk, and blood, and gene expression of AA transporters were determined.Results: Compared with the Control or Ala group, the infusion of Arg led to greater expression of AA transporters(SLC7 A2 and SLC7 A8) and apparent uptake of free AA in the mammary gland, and was accompanied by greater milk yield, milk protein yield and milk efficiency(calculated by dividing milk yield over feed intake), together with lower concentration of urea N [regarded as an indicator of N utilization efficiency(NUE)] in blood and milk. Furthermore, in the cows infused with Arg, the NUE was higher and the concentration of urea N in urine was lower than those in the Ala group, although no differences were detected in NUE and urea N in urine between the Control and Arg group.The infusion of Ala had no effect on those indices compared with the Control.Conclusions: Overall, enhancing the post-ruminal supply of Arg via the jugular vein had a positive effect on the synthesis of milk protein at least in part by increasing gene expression of some AA transporters and uptake of free AA by mammary gland.展开更多
Dietary nutrient manipulation(e.g.protein fractions)could lower the environmental footprints of ruminants,especially reactive nitrogen(N).This study investigated the impacts of dietary soluble protein(SP)levels with d...Dietary nutrient manipulation(e.g.protein fractions)could lower the environmental footprints of ruminants,especially reactive nitrogen(N).This study investigated the impacts of dietary soluble protein(SP)levels with decreased crude protein(CP)on intestinal N absorption,hindgut N metabolism,fecal microbiota and metabolites,and their linkage with N metabolism phenotype.Thirty-two male Hu sheep,with an age of six months and an initial BW of 40.37±1.18 kg,were randomly assigned to four dietary groups.The control diet(CON),aligning with NRC standards,maintained a CP content of 16.7%on a dry matter basis.Conversely,the experimental diets(LPA,LPB,and LPC)featured a 10%reduction in CP compared with CON,accompanied by SP adjustments to 21.2%,25.9%,and 29.4%of CP,respectively.Our results showed that low-protein diets led to significant reductions in the concentrations of plasma creatinine,ammonia,urea N,and fecal total short-chain fatty acids(SCFA)(P<0.05).Notably,LPB and LPC exhibited increased total SCFA and propionate concentrations compared with LPA(P<0.05).The enrichment of the Prevotella genus in fecal microbiota associated with energy metabolism and amino acid(AA)biosynthesis pathways was evident with SP levels in low-protein diets of approximately 25%to 30%.Moreover,LPB and LPC diets demonstrated a decrease in fecal NH_(4)^(+) eN and NO_(2) eN contents as well as urease activity,compared with CON(P<0.05).Concomitantly,reductions in fecal glutamic acid dehydrogenase gene(gdh),nitrite reductase gene(nirS),and nitric oxide reductase gene(norB)abundances were observed(P<0.05),pointing towards a potential reduction in reactive N production at the source.Of significance,the up-regulation of mRNA abundance of AA and peptide transporters in the small intestine(duodenum,jejunum,and ileum)and the elevated concentration of plasma AA(e.g.arginine,methionine,aspartate,glutamate,etc.)underscored the enhancement of N absorption and N efficiency.In summary,a 10%reduction in CP,coupled with an SP level of approximately 25%to 30%,demonstrated the potential to curtail reactive N emissions through fecal Prevotella enrichment and improve intestinal energy and N utilization efficiency.展开更多
This study aimed to investigate the effects of dietary supplementation of underfed Hu ewes from d 35 to110 of gestation with either rumen-protected L-arginine(RP-Arg)or N-carbamylglutamate(NCG)on placental amino acid(...This study aimed to investigate the effects of dietary supplementation of underfed Hu ewes from d 35 to110 of gestation with either rumen-protected L-arginine(RP-Arg)or N-carbamylglutamate(NCG)on placental amino acid(AA)transport,angiogenic gene expression,and steroid anabolism.On d 35 of gestation,32 Hu ewes carrying twin fetuses were randomly divided into four treatment groups,each consisting of eight ewes,and were fed the following diets:A diet providing 100%of NRC’s nutrient requirements for pregnant ewes(CON);A diet providing 50%of NRC’s nutrient requirements for pregnant ewes(RES);RES diet plus 5 g/d NCG(RES+NCG);or RES diet plus 20 g/d RP-Arg(RES+ARG).On the d 110 of pregnancy,blood samples were taken from the mother,and samples were collected from type A cotyledons(COT;the fetal portions of the placenta).The levels of 17β-estradiol and progesterone in the maternal serum and both the capillary area density(CAD)and capillary surface density(CSD)in type A COT were decreased in response to Arg or NCG supplementation when compared to the RES group.The concentrations of arginine,leucine,putrescine and spermidine in type A COT were higher(P<0.05)in the RES+ARG or RES+NCG group than in the RES group.The mRNA expression levels of inducible nitric oxide synthase(iNOS)and solute carrier family 15,member 1(SLC15A1)were increased(P<0.05)while those of progesterone receptor(PGR)and fibroblast growth factor 2(FGF2)were decreased in type A COT by supplementation with either NCG or RP-Arg compared to the RES group.The results suggest that providing underfed pregnant ewes from d 35 to 110 of gestation with a diet supplemented with NCG or RP-Arg improves placental AA transport,and reduces the expression of angiogenic growth factor genes and steroid anabolism,leading to better fetal development.展开更多
This study aimed to explore whether dietary rumen-protected L-arginine(RP-Arg)or N-carbamylglutamate(NCG)supplementation to feed-restricted pregnant ewes counteracts fetal hepatic inflammation and innate immune dysfun...This study aimed to explore whether dietary rumen-protected L-arginine(RP-Arg)or N-carbamylglutamate(NCG)supplementation to feed-restricted pregnant ewes counteracts fetal hepatic inflammation and innate immune dysfunction associated with intrauterine growth retardation(IUGR)in ovine fetuses.On d 35 of pregnancy,twin-bearing Hu ewes(n=32)were randomly assigned to 4 treatment groups(8 ewes and 16 fetuses per group)and fed diets containing 100%of the NRC requirements(CON),50%of the NRC requirements(RES),RES+RP-Arg(20 g/d)(RESA),or RES+NCG(5 g/d)(RESN).At 08:00 on d 110 of gestation,fetal blood and liver tissue samples were collected.The levels of triglyceride,free fatty acid,cholesterol andβ-hydroxybutyrate in the fetal blood of RESA and RESN groups were lower(P<0.05)than those of the RES group,but were higher(P<0.05)than those of the CON group.The interleukin(IL)-6 and IL-1 levels in fetal blood and liver tissue as well as the myeloid differentiation primary response 88(MyD88),transforming growth factorβ(TGFβ),and nuclear factor kappa B(NF-κB)mRNA levels in the fetal liver were decreased(P<0.05)by the NCG or RP-Arg supplementation compared to the RES treatment.Similarly,the toll-like receptor(TLR)-4,MyD88,TGFβ,and p-c-Jun N-terminal kinase(JNK)protein levels in the fetal liver were reduced(P<0.05)in the NCG and RP-Arg-supplemented groups compared to the RES group.These results showed that dietary supplementation of RP-Arg or NCG to underfed pregnant ewes could protect against IUGR fetal hepatic inflammation via improving lipid metabolism,down-regulating the TLR-4 and the inflammatory JNK and NF-icB signaling pathways,and decreasing cytokine production in ovine fetal blood and liver tissue.展开更多
Previous studies have revealed that dietary N-carbamylglutamate(NCG)or L-arginine(Arg)improves small intestinal integrity and immune function in suckling Hu lambs that have experienced intrauterine growth retardation(...Previous studies have revealed that dietary N-carbamylglutamate(NCG)or L-arginine(Arg)improves small intestinal integrity and immune function in suckling Hu lambs that have experienced intrauterine growth retardation(IUGR).Whether these nutrients alter redox status and apoptosis in the colon of IUGR lambs is still unknown.This study,therefore,aimed at investigating whether dietary supplementation of Arg or NCG alters colonic redox status,apoptosis and endoplasmic reticulum(ER)stress and the underlying mechanism of these alterations in IUGR suckling Hu lambs.Forty-eight 7-d old Hu lambs,including 12 with normal birth weight(4.25±0.14 kg)and 36 with IUGR(3.01±0.12 kg),were assigned to 4 treatment groups(n=12 each;6 males and 6 females)for 3 weeks.The treatment groups were control(CON),IUGR,IUGR+Arg and IUGR+NCG.Relative to IUGR lambs,superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)content,as well as proliferation index,were higher(P<0.05)whereas reactive oxygen species(ROS),malondialdehyde(MDA)levels and apoptotic cell numbers were lower(P<0.05)in colonic tissue for both IUGR+Arg and NCG lambs.Both m RNA and protein levels of C/EBP homologous protein 10(CHOP10),B-cell lymphoma/leukaemia 2(Bcl-2)-associated X protein(Bax),apoptosis antigen 1(Fas),activating transcription factor 6(ATF6),caspase 3,and glucose-regulated protein 78(GRP78)were lower(P<0.05)while glutathione peroxidase 1(GPx1),Bcl-2 and catalase(CAT)levels were higher(P<0.05)in colonic tissue for IUGR+Arg and IUGR+NCG lambs compared with IUGR lambs.Based on our results,dietary NCG or Arg supplementation can improve colonic redox status and suppress apoptosis via death receptor-dependent,mitochondrial and ER stress pathways in IUGR suckling lambs.展开更多
Due to regulation by circadian rhythm, the lactation of the mammary gland has rhythmicity. As one of prominent members of period protein family which regulates biological rhythms, PER2 plays an important role in devel...Due to regulation by circadian rhythm, the lactation of the mammary gland has rhythmicity. As one of prominent members of period protein family which regulates biological rhythms, PER2 plays an important role in developing the milk duct and maintaining the polarity and the morphology of the mammary epithelium; at the same time, it is also closely related with the metabolism of milk protein and milk fat. This paper summarized recent researches on PER2 gene and related researches on mammary gland development and metabolism to provide some information for the studies of the theory and technology on physiological functions of the mammary gland and milk quality control.展开更多
Our previous studies demonstrated that prenatal in utero growth restriction impairs postnatal intestinal function.Thus,improving postpartal intestinal absorption capacity and growth by manipulating the maternal diet p...Our previous studies demonstrated that prenatal in utero growth restriction impairs postnatal intestinal function.Thus,improving postpartal intestinal absorption capacity and growth by manipulating the maternal diet prepartum is of importance.This work was conducted to determine whether supplementation of N-carbamylglutamate(NCG)or rumen-protected L-arginine(RP-Arg)increased fetal intestinal amino acid(AA)profiles in intrauterine growth retardation(IUGR)fetuses.On d 35 of gestation,Hu ewes(n=32)carrying twin fetuses were randomized into 4 groups(8 ewes and 16 fetuses in each group),where diets were as follows:100%of nutrient requirements recommended by National Research Council(NRC,2007)(CON);50%of nutrient requirements recommended by NRC(2007)(RES);RES+RPArg(20 g/d),(RES+ARG);and RES+NCG(5 g/d),(RES+NCG).On d 110 of gestation,both fetal and maternal tissues were collected and weighed.Compared with RES,solute carrier family 1,member 5(SLC1A5)was upregulated(P<0.05)within fetal jejunum,duodenum and ileum when supplementing NCG and RP-Arg.Relative to RES,RP-Arg or NCG supplementation to RES resulted in upregulation(P<0.05)of peptide transporter 1 protein abundance within the fetal ileum.NCG or RP-Arg supplementation to RES also upregulated phosphorylated mechanistic target of rapamycin(pmTOR)-to-mTOR ratio in the fetal ileum induced by IUGR(P<0.05).As a result,during IUGR,supplementation of Arg or NCG affected intestinal AA profiles in the fetus in part through controlling mTOR signal transduction as well as AA and peptide transport.Future studies should be conducted to understand the role(if any)of the placenta on the improvement of growth and AA profiles independent of the fetal intestine.This would help demonstrate the relative contribution of intestinal uptake in fetal life.展开更多
The objective of this study was to investigate the effects of dietary administration of L-arginine(Arg)or N-carbamylglutamate(NCG)on hepatic energy status and mitochondrial functions in suckling Hu lambs with intraute...The objective of this study was to investigate the effects of dietary administration of L-arginine(Arg)or N-carbamylglutamate(NCG)on hepatic energy status and mitochondrial functions in suckling Hu lambs with intrauterine growth retardation(IUGR).Forty-eight newborn Hu lambs of 7 d old were allocated into 4 treatment groups of 12 lambs each,in triplicate with 4 lambs per replicate(2 males and 2 females)as follows:CON(lambs of normal birth weight,4.25±0.14 kg),IUGR(3.01±0.12 kg),IUGR+1%Arg(2.99±0.13 kg),or IUGR+0.1%NCG(3.03±0.11 kg).The experiment lasted for 21 d,until d 28 after birth,and all lambs were fed milk replacer as a basal diet.Compared with IUGR lambs,NCG or Arg administration increased(P<0.05)the adenosine triphosphate(ATP)level and the activities of com-plexes I/III/IV,isocitrate dehydrogenase and citrate synthase in the liver.Compared with CON lambs,the relative mRNA levels of adenosine monophosphate-activated protein kinaseα1(AMPKα1),peroxisome proliferator-activated receptorγcoactivator-1α(PGC1α)and transcription factor A(TFAM)were increased(P<0.05)in the liver of IUGR lambs,but were decreased(P<0.05)in the liver of NCG-or Arg-treated lambs compared with those in the IUGR lambs.Compared with IUGR lambs,NCG or Arg administration decreased(P<0.05)the total AMPKα(tAMPKα)-to-phosphorylated AMPKα(pAMPKα)ratio and the protein expression of PGC1αand TFAM.The results suggested that dietary Arg or NCG supplements improved hepatic energy status and mitochondrial function and inhibited the AMPK-PGC1α-TFAM pathway in IUGR suckling lambs.展开更多
基金supported by the fund for the National 14th Five-Year Plan Key Research and Development Program(2021YFD1600702)XPCC Agricultural Science and Technology Innovation Project(NCG202232)the Top Talents Award Plan of Yangzhou University(2020)。
文摘Background Exposure to bisphenol A(BPA),an environmental pollutant known for its endocrine-disrupting properties,during gestation has been reported to increase the risk of fetal growth restriction(FGR)in an ovine model of pregnancy.We hypothesized that the FGR results from the BPA-induced insufficiency and barrier dysfunction of the placenta,oxidative stress,inflammatory responses,autophagy and endoplasmic reticulum stress(ERS).However,precise mechanisms underlying the BPA-induced placental dysfunction,and subsequently,FGR,as well as the potential involvement of placental ERS in these complications,remain to be investigated.Methods In vivo experiment,16 twin-pregnant(from d 40 to 130 of gestation)Hu ewes were randomly distributed into two groups(8 ewes each).One group served as a control and received corn oil once a day,whereas the other group received BPA(5 mg/kg/d as a subcutaneous injection).In vitro study,ovine trophoblast cells(OTCs)were exposed to 4 treatments,6 replicates each.The OTCs were treated with 400μmol/L BPA,400μmol/L BPA+0.5μg/m L tunicamycin(Tm;ERS activator),400μmol/L BPA+1μmol/L 4-phenyl butyric acid(4-PBA;ERS antagonist)and DMEM/F12 complete medium(control),for 24 h.Results In vivo experiments,pregnant Hu ewes receiving the BPA from 40 to 130 days of pregnancy experienced a decrease in placental efficiency,progesterone(P4)level and fetal weight,and an increase in placental estrogen(E2)level,together with barrier dysfunctions,OS,inflammatory responses,autophagy and ERS in type A cotyledons.In vitro experiment,the OTCs exposed to BPA for 24 h showed an increase in the E2 level and related protein and gene expressions of autophagy,ERS,pro-apoptosis and inflammatory response,and a decrease in the P4 level and the related protein and gene expressions of antioxidant,anti-apoptosis and barrier function.Moreover,treating the OTCs with Tm aggravated BPA-induced dysfunction of barrier and endocrine(the increased E2 level and decreased P4 level),OS,inflammatory responses,autophagy,and ERS.However,treating the OTCs with 4-PBA reversed the counteracted effects of Tm mentioned above.Conclusions In general,the results reveal that BPA exposure can cause ERS in the ovine placenta and OTCs,and ERS induction might aggravate BPA-induced dysfunction of the placental barrier and endocrine,OS,inflammatory responses,and autophagy.These data offer novel mechanistic insights into whether ERS is involved in BPA-mediated placental dysfunction and fetal development.
基金supported by projects from the National Key Research and Development Program of China(2018YFD0502100)China Scholarship Council–The University of Western Australia Joint Scholarship(201708320259)+1 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)P.R.China
文摘Background: Enhancing the post-ruminal supply of arginine(Arg), a semi-essential amino acid(AA), elicits positive effects on milk production. Our objective was to determine the effects of Arg infusion on milk production parameters and aspects of nitrogen(N) absorption and utilization in lactating dairy cows. Six lactating Chinese Holstein cows of similar body weight(508 ± 14 kg), body condition score(3.0 ± 0), parity(4.0 ± 0), milk yield(30.6 ±1.8 kg) and days in milk(20 ± 2 d) were randomly assigned to 3 treatments in a replicated 3 × 3 Latin square design with 21 d for each period(1 week for infusion and 2 weeks for washout). Treatments were 1) Control: saline;2) Arg group: saline + 9.42 g/L L-Arg;3) Alanine(Ala) group: saline + 19.31 g/L L-Ala(iso-nitrogenous to the Arg group). Milk production and composition, dry matter intake, apparent absorption of N, profiles of amino acids(AA) in blood,urea N in urine, milk, and blood, and gene expression of AA transporters were determined.Results: Compared with the Control or Ala group, the infusion of Arg led to greater expression of AA transporters(SLC7 A2 and SLC7 A8) and apparent uptake of free AA in the mammary gland, and was accompanied by greater milk yield, milk protein yield and milk efficiency(calculated by dividing milk yield over feed intake), together with lower concentration of urea N [regarded as an indicator of N utilization efficiency(NUE)] in blood and milk. Furthermore, in the cows infused with Arg, the NUE was higher and the concentration of urea N in urine was lower than those in the Ala group, although no differences were detected in NUE and urea N in urine between the Control and Arg group.The infusion of Ala had no effect on those indices compared with the Control.Conclusions: Overall, enhancing the post-ruminal supply of Arg via the jugular vein had a positive effect on the synthesis of milk protein at least in part by increasing gene expression of some AA transporters and uptake of free AA by mammary gland.
基金supported by Bintuan Science and Technology Program (2023AB078)Bintuan Agricultural Innovation Project (NCG202232)+2 种基金China Scholarship Council (NO.202208320271)Postgraduate Research&Practice Innovation Program of Jiangsu Province (KYCX22_3532,SJCX23_1991)the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD),China.
文摘Dietary nutrient manipulation(e.g.protein fractions)could lower the environmental footprints of ruminants,especially reactive nitrogen(N).This study investigated the impacts of dietary soluble protein(SP)levels with decreased crude protein(CP)on intestinal N absorption,hindgut N metabolism,fecal microbiota and metabolites,and their linkage with N metabolism phenotype.Thirty-two male Hu sheep,with an age of six months and an initial BW of 40.37±1.18 kg,were randomly assigned to four dietary groups.The control diet(CON),aligning with NRC standards,maintained a CP content of 16.7%on a dry matter basis.Conversely,the experimental diets(LPA,LPB,and LPC)featured a 10%reduction in CP compared with CON,accompanied by SP adjustments to 21.2%,25.9%,and 29.4%of CP,respectively.Our results showed that low-protein diets led to significant reductions in the concentrations of plasma creatinine,ammonia,urea N,and fecal total short-chain fatty acids(SCFA)(P<0.05).Notably,LPB and LPC exhibited increased total SCFA and propionate concentrations compared with LPA(P<0.05).The enrichment of the Prevotella genus in fecal microbiota associated with energy metabolism and amino acid(AA)biosynthesis pathways was evident with SP levels in low-protein diets of approximately 25%to 30%.Moreover,LPB and LPC diets demonstrated a decrease in fecal NH_(4)^(+) eN and NO_(2) eN contents as well as urease activity,compared with CON(P<0.05).Concomitantly,reductions in fecal glutamic acid dehydrogenase gene(gdh),nitrite reductase gene(nirS),and nitric oxide reductase gene(norB)abundances were observed(P<0.05),pointing towards a potential reduction in reactive N production at the source.Of significance,the up-regulation of mRNA abundance of AA and peptide transporters in the small intestine(duodenum,jejunum,and ileum)and the elevated concentration of plasma AA(e.g.arginine,methionine,aspartate,glutamate,etc.)underscored the enhancement of N absorption and N efficiency.In summary,a 10%reduction in CP,coupled with an SP level of approximately 25%to 30%,demonstrated the potential to curtail reactive N emissions through fecal Prevotella enrichment and improve intestinal energy and N utilization efficiency.
基金The research was supported by the fund for the Top Talents Award Plan of Yangzhou University(2020)the Cyanine Project of Yangzhou University(2020).
文摘This study aimed to investigate the effects of dietary supplementation of underfed Hu ewes from d 35 to110 of gestation with either rumen-protected L-arginine(RP-Arg)or N-carbamylglutamate(NCG)on placental amino acid(AA)transport,angiogenic gene expression,and steroid anabolism.On d 35 of gestation,32 Hu ewes carrying twin fetuses were randomly divided into four treatment groups,each consisting of eight ewes,and were fed the following diets:A diet providing 100%of NRC’s nutrient requirements for pregnant ewes(CON);A diet providing 50%of NRC’s nutrient requirements for pregnant ewes(RES);RES diet plus 5 g/d NCG(RES+NCG);or RES diet plus 20 g/d RP-Arg(RES+ARG).On the d 110 of pregnancy,blood samples were taken from the mother,and samples were collected from type A cotyledons(COT;the fetal portions of the placenta).The levels of 17β-estradiol and progesterone in the maternal serum and both the capillary area density(CAD)and capillary surface density(CSD)in type A COT were decreased in response to Arg or NCG supplementation when compared to the RES group.The concentrations of arginine,leucine,putrescine and spermidine in type A COT were higher(P<0.05)in the RES+ARG or RES+NCG group than in the RES group.The mRNA expression levels of inducible nitric oxide synthase(iNOS)and solute carrier family 15,member 1(SLC15A1)were increased(P<0.05)while those of progesterone receptor(PGR)and fibroblast growth factor 2(FGF2)were decreased in type A COT by supplementation with either NCG or RP-Arg compared to the RES group.The results suggest that providing underfed pregnant ewes from d 35 to 110 of gestation with a diet supplemented with NCG or RP-Arg improves placental AA transport,and reduces the expression of angiogenic growth factor genes and steroid anabolism,leading to better fetal development.
基金supported by the fund for the National Natural Science Foundation of China(31902180)the Top Talents Award Plan of Yangzhou University(2019)+2 种基金the Cyanine Project of Yangzhou University(2020)the funds from State Key Laboratory of Sheep Genetic Improvement and Healthy Production(2021ZD07)Yangzhou University Science and Technology Innovation Foundation(2019CXJ152)。
文摘This study aimed to explore whether dietary rumen-protected L-arginine(RP-Arg)or N-carbamylglutamate(NCG)supplementation to feed-restricted pregnant ewes counteracts fetal hepatic inflammation and innate immune dysfunction associated with intrauterine growth retardation(IUGR)in ovine fetuses.On d 35 of pregnancy,twin-bearing Hu ewes(n=32)were randomly assigned to 4 treatment groups(8 ewes and 16 fetuses per group)and fed diets containing 100%of the NRC requirements(CON),50%of the NRC requirements(RES),RES+RP-Arg(20 g/d)(RESA),or RES+NCG(5 g/d)(RESN).At 08:00 on d 110 of gestation,fetal blood and liver tissue samples were collected.The levels of triglyceride,free fatty acid,cholesterol andβ-hydroxybutyrate in the fetal blood of RESA and RESN groups were lower(P<0.05)than those of the RES group,but were higher(P<0.05)than those of the CON group.The interleukin(IL)-6 and IL-1 levels in fetal blood and liver tissue as well as the myeloid differentiation primary response 88(MyD88),transforming growth factorβ(TGFβ),and nuclear factor kappa B(NF-κB)mRNA levels in the fetal liver were decreased(P<0.05)by the NCG or RP-Arg supplementation compared to the RES treatment.Similarly,the toll-like receptor(TLR)-4,MyD88,TGFβ,and p-c-Jun N-terminal kinase(JNK)protein levels in the fetal liver were reduced(P<0.05)in the NCG and RP-Arg-supplemented groups compared to the RES group.These results showed that dietary supplementation of RP-Arg or NCG to underfed pregnant ewes could protect against IUGR fetal hepatic inflammation via improving lipid metabolism,down-regulating the TLR-4 and the inflammatory JNK and NF-icB signaling pathways,and decreasing cytokine production in ovine fetal blood and liver tissue.
基金funded by the National Natural Science Foundation of China(31902180)the Top Talents Award Plan of Yangzhou University(2020)the Cyanine Project of Yangzhou University(2020)。
文摘Previous studies have revealed that dietary N-carbamylglutamate(NCG)or L-arginine(Arg)improves small intestinal integrity and immune function in suckling Hu lambs that have experienced intrauterine growth retardation(IUGR).Whether these nutrients alter redox status and apoptosis in the colon of IUGR lambs is still unknown.This study,therefore,aimed at investigating whether dietary supplementation of Arg or NCG alters colonic redox status,apoptosis and endoplasmic reticulum(ER)stress and the underlying mechanism of these alterations in IUGR suckling Hu lambs.Forty-eight 7-d old Hu lambs,including 12 with normal birth weight(4.25±0.14 kg)and 36 with IUGR(3.01±0.12 kg),were assigned to 4 treatment groups(n=12 each;6 males and 6 females)for 3 weeks.The treatment groups were control(CON),IUGR,IUGR+Arg and IUGR+NCG.Relative to IUGR lambs,superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)content,as well as proliferation index,were higher(P<0.05)whereas reactive oxygen species(ROS),malondialdehyde(MDA)levels and apoptotic cell numbers were lower(P<0.05)in colonic tissue for both IUGR+Arg and NCG lambs.Both m RNA and protein levels of C/EBP homologous protein 10(CHOP10),B-cell lymphoma/leukaemia 2(Bcl-2)-associated X protein(Bax),apoptosis antigen 1(Fas),activating transcription factor 6(ATF6),caspase 3,and glucose-regulated protein 78(GRP78)were lower(P<0.05)while glutathione peroxidase 1(GPx1),Bcl-2 and catalase(CAT)levels were higher(P<0.05)in colonic tissue for IUGR+Arg and IUGR+NCG lambs compared with IUGR lambs.Based on our results,dietary NCG or Arg supplementation can improve colonic redox status and suppress apoptosis via death receptor-dependent,mitochondrial and ER stress pathways in IUGR suckling lambs.
基金supported by the Natural Science Foundation(BK20151312,BK20141270)2015 University Student Innovation Training Program(201511117037)of Jiangsu ProvincePriority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)P.R.China
文摘Due to regulation by circadian rhythm, the lactation of the mammary gland has rhythmicity. As one of prominent members of period protein family which regulates biological rhythms, PER2 plays an important role in developing the milk duct and maintaining the polarity and the morphology of the mammary epithelium; at the same time, it is also closely related with the metabolism of milk protein and milk fat. This paper summarized recent researches on PER2 gene and related researches on mammary gland development and metabolism to provide some information for the studies of the theory and technology on physiological functions of the mammary gland and milk quality control.
基金The research was supported by the fund for the National Natural Science Foundation of China(31902180)the Science and Technology Innovation Project of Yangzhou University(2019CXJ152)+2 种基金the Top Talents Award Plan of Yangzhou University(2019)the funds from State Key Laboratory of Sheep Genetic Improvement and Healthy Production(2021ZD07)the Cyanine Project of Yangzhou University(2020).
文摘Our previous studies demonstrated that prenatal in utero growth restriction impairs postnatal intestinal function.Thus,improving postpartal intestinal absorption capacity and growth by manipulating the maternal diet prepartum is of importance.This work was conducted to determine whether supplementation of N-carbamylglutamate(NCG)or rumen-protected L-arginine(RP-Arg)increased fetal intestinal amino acid(AA)profiles in intrauterine growth retardation(IUGR)fetuses.On d 35 of gestation,Hu ewes(n=32)carrying twin fetuses were randomized into 4 groups(8 ewes and 16 fetuses in each group),where diets were as follows:100%of nutrient requirements recommended by National Research Council(NRC,2007)(CON);50%of nutrient requirements recommended by NRC(2007)(RES);RES+RPArg(20 g/d),(RES+ARG);and RES+NCG(5 g/d),(RES+NCG).On d 110 of gestation,both fetal and maternal tissues were collected and weighed.Compared with RES,solute carrier family 1,member 5(SLC1A5)was upregulated(P<0.05)within fetal jejunum,duodenum and ileum when supplementing NCG and RP-Arg.Relative to RES,RP-Arg or NCG supplementation to RES resulted in upregulation(P<0.05)of peptide transporter 1 protein abundance within the fetal ileum.NCG or RP-Arg supplementation to RES also upregulated phosphorylated mechanistic target of rapamycin(pmTOR)-to-mTOR ratio in the fetal ileum induced by IUGR(P<0.05).As a result,during IUGR,supplementation of Arg or NCG affected intestinal AA profiles in the fetus in part through controlling mTOR signal transduction as well as AA and peptide transport.Future studies should be conducted to understand the role(if any)of the placenta on the improvement of growth and AA profiles independent of the fetal intestine.This would help demonstrate the relative contribution of intestinal uptake in fetal life.
基金supported by the fund for the National Natural Science Foundation of China(31902180)the Research Project of Natural Science Foundation of Jiangsu Province(BK20170488)+3 种基金the China Postdoctoral Science Foundation(2017M610358)the Science and Technology Innovation Project of Yangzhou University(2019CXJ152)the Top Talents Award Plan of Yangzhou University(2020)the Cyanine Project of Yangzhou University(2020)
文摘The objective of this study was to investigate the effects of dietary administration of L-arginine(Arg)or N-carbamylglutamate(NCG)on hepatic energy status and mitochondrial functions in suckling Hu lambs with intrauterine growth retardation(IUGR).Forty-eight newborn Hu lambs of 7 d old were allocated into 4 treatment groups of 12 lambs each,in triplicate with 4 lambs per replicate(2 males and 2 females)as follows:CON(lambs of normal birth weight,4.25±0.14 kg),IUGR(3.01±0.12 kg),IUGR+1%Arg(2.99±0.13 kg),or IUGR+0.1%NCG(3.03±0.11 kg).The experiment lasted for 21 d,until d 28 after birth,and all lambs were fed milk replacer as a basal diet.Compared with IUGR lambs,NCG or Arg administration increased(P<0.05)the adenosine triphosphate(ATP)level and the activities of com-plexes I/III/IV,isocitrate dehydrogenase and citrate synthase in the liver.Compared with CON lambs,the relative mRNA levels of adenosine monophosphate-activated protein kinaseα1(AMPKα1),peroxisome proliferator-activated receptorγcoactivator-1α(PGC1α)and transcription factor A(TFAM)were increased(P<0.05)in the liver of IUGR lambs,but were decreased(P<0.05)in the liver of NCG-or Arg-treated lambs compared with those in the IUGR lambs.Compared with IUGR lambs,NCG or Arg administration decreased(P<0.05)the total AMPKα(tAMPKα)-to-phosphorylated AMPKα(pAMPKα)ratio and the protein expression of PGC1αand TFAM.The results suggested that dietary Arg or NCG supplements improved hepatic energy status and mitochondrial function and inhibited the AMPK-PGC1α-TFAM pathway in IUGR suckling lambs.
