Effects of maternal methyl donor intake during pregnancy on ileum methylation and function in an intrauterine growth restriction pig model

Background Intrauterine growth retardation(IUGR)affects intestinal growth,morphology,and function,which leads to poor growth performance and high mortality.The present study explored whether maternal dietary methyl donor(MET)supplementation alleviates IUGR and enhances offspring’s growth performance by improving intestinal growth,function,and DNA methylation of the ileum in a porcine IUGR model.Methods Forty multiparous sows were allocated to the control or MET diet groups from mating until delivery.After farrowing,8 pairs of IUGR and normal birth weight piglets from 8 litters were selected for sampling before suckling colostrum.Results The results showed that maternal MET supplementation tended to decrease the IUGR incidence and increased the average weaning weight of piglets.Moreover,maternal MET supplementation significantly reduced the plasma concentrations of isoleucine,cysteine,urea,and total amino acids in sows and newborn pig-lets.It also increased lactase and sucrase activity in the jejunum of newborn piglets.MET addition resulted in lower ileal methionine synthase activity and increased betaine homocysteine S-methyltransferase activity in the ileum of newborn piglets.DNA methylation analysis of the ileum showed that MET supplementation increased the methyla-tion level of DNA CpG sites in the ileum of newborn piglets.Down-regulated differentially methylated genes were enriched in folic acid binding,insulin receptor signaling pathway,and endothelial cell proliferation.In contrast,up-regulated methylated genes were enriched in growth hormone receptor signaling pathway and nitric oxide biosyn-thetic process.Conclusions Maternal MET supplementation can reduce the incidence of IUGR and increase the weaning litter weight of piglets,which may be associated with better intestinal function and methylation status.

Effects of Intrauterine Growth Restriction on Gene Expression in Small Intestine of Piglets

[ Objective] To profile the differentially expressed genes in small intestine between piglets with intrauterine growth restriction （IUGR）, describe the relationships between growth performance and gene expression in IUGR piglets, and thus provide a theoretical basis for further research. [Metbed] Eight suckling piglets at the age of 21 d Efour with normal body weight （NBW） of （1 503 ± 310） g and four with low BW of （806 ±35） g] were killed, and the intestinal samples were collected. Gene expression was detected by Affymetrix Porcine GeneChip and further confirmed by quantitative real-time PCR. [ ReseltJ Microarray analysis showed that there were 156 differentially expressed genes in the small intestine between the IUGR piglets and the age-matched NBW piglets, including 61 down-regulated genes and 95 up-regulated genes, The up-regulated genes included protein tyrosine phosphatase, myosin, troponin, heat shock protein, metallothionein, arginine vasopressin-induced 1, ribosomal protein L6, apoptosls antagonizing transcription factor, muscle creatine kinase, mannosidase, lysozyme, folliculin, urate transporterchannel protein, pyrroline-5-carboxylate reductese-like, and adenine phosphor-dbosyltransferase. The down-regulated genes included protein kinase, arachidohate 12-1ipoxygenase, transcription factor A, GTP-GDP dissociation stimulator 1, serine （or cysteine） proteinase inhibitor, fetuin, dolichol-phosphate-mannose synthase, apolipoprotein H, argininosuccinate synthetase 1, iron-regulated transporter, alpha-2-macroglobulin, immunoglobulin superfamily, thioltransferase, and guanylate binding protein 2. The gene expression profile changed in the small intestine of piglets with intrauterine growth restriction, providing a theoretical basis for eady intervention in growth restriction.

Antenatal taurine reduces cerebral cell apoptosis in fetal rats with intrauterine growth restriction

From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12th day of pregnancy, 300 mg/kg taurine was daily added to food until spontaneous delivery occurred. Brain tissues from normal neonatal rats at 6 hours after delivery, neonatal rats with intrauterine growth restriction, and neo- natal rats with intrauterine growth restriction undergoing taurine supplement were obtained for fur- ther experiments. The terminal deoxyribonucleotidyl transferase （TdT）-mediated biotin-16-dUTP nick-end labeling assay revealed that the number of apoptotic cells in the brain tissue of neonatal rats with intrauterine growth restriction significantly increased. Taurine supplement in pregnant rats reduced cell apoptosis in brain tissue from neonatal rats with intrauterine growth restriction. Immu- nohistochemical staining revealed that taurine supplement increased glial cell line-derived neuro- trophic factor expression and decreased caspase-3 expression in the cerebral cortex of intrauterine growth-restricted fetal rats. These results indicate that taurine supplement reduces cell apoptosis through the glial cell line-derived neurotrophic factor-caspase-3 signaling pathway, resulting in a protective effect on the intrauterine growth-restricted fetal rat brain.

Intrauterine growth restriction alters growth performance, plasma hormones,and small intestinal microbial communities in growing-finishing pigs

Background: The interaction of the gut microbiota with key metabolic and physiological processes may be associated with poor growth outcomes in animals born with intrauterine growth restriction(IUGR).Results: Growth performance, plasma hormone concentrations, and intestinal microbiota composition were analyzed in IUGR pigs and in normal birth weight(NBW) pigs when the NBW pigs reached 25, 50, and 100 kg of body weight(BW). Compared to NBW pigs, IUGR pigs had lower initial, weaned, and final BW, and lower average daily gain and average daily feed intake in all the considered time points. In the 25 kg BW group, IUGR pigs had higher concentrations of plasma ghrelin and pancreatic polypeptide(PP), but lower insulin concentration than NBW pigs, while the situation was reversed in the 50 kg BW group. As compared to NBW pigs, IUGR pigs had higher microbial alpha diversity in the jejunum and ileum;in the 50 and 100 kg BW groups, IUGR pigs had higher Firmicutes abundance but lower Proteobacteria abundance in the jejunum, and lower Lactobacillus abundance in the jejunum and ileum;in the 25 kg BW group, IUGR pigs showed higher unclassified Ruminococcaceae abundance in the ileum;and in 25 and 50 kg BW groups, IUGR pigs showed lower Ochrobactrum abundance in the jejunum.Spearman's correlation revealed that Lactobacillus was negatively correlated with growth performance, while unclassified Ruminococcaceae was positively correlated. Predictive metagenomic analysis detected significantly different expression of genes in the intestinal microbiota between IUGR and NBW pigs, suggesting different metabolic capabilities between the two groups.Conclusions: Growing-finishing IUGR pigs showed lower growth performance, higher microbial alpha diversity, and differences in plasma hormone concentrations compared to NBW pigs. Alterations in the abundance of Firmicutes,Proteobacteria, Ruminococcaceae, Lactobacillus, and Ochrobactrum in the small intestine may be associated with IUGR, and may therefore serve as a future target for gut microbiota intervention in growing-finishing IUGR pigs.

Intrauterine growth restriction and genetic determinantsexisting findings, problems, and further direction

Fetal growth is determined largely by the nutrient supply, placental transport function, and growth hormones. Recently, gene mutation and expression, especially of those genes associated with the proteins that are related to the fetal growth, have been reported to play an important role in the development of intrauterine growth restriction(IUGR). Fetal growth epigenetics, a new concept in fetal growth, has resulted from studies on fetal programing. This paper outlines the findings of our serial studies on IUGR, and summarizes data on IUGR animal models, placental function in transferring nutrients, cell proliferation dynamics in IUGR, and experimental treatment of IUGR. We review genetic approaches to IUGR, especially those relating to growth factor genes, angiotensinogen genes and other gene mutations. We also discuss the epigenetics of fetal growth and future study directions on fetal growth restriction. These should be valuable in elucidating the mechanisms employed by the fetus and in helping to develop interventional strategies that might prevent the development of IUGR.

The Proteome Landscape of Human Placentas for Monochorionic Twins with Selective Intrauterine Growth Restriction

In perinatal medicine,intrauterine growth restriction(IUGR)is one of the greatest challenges.The etiology of IUGR is multifactorial,but most cases are thought to arise from placental insufficiency.However,identifying the placental cause of IUGR can be difficult due to numerous confounding factors.Selective IUGR(sIUGR)would be a good model to investigate how impaired placentation affects fetal development,as the growth discordance between monochorionic twins cannot be explained by confounding genetic or maternal factors.Herein,we constructed and analyzed the placental proteomic profiles of IUGR twins and normal cotwins.Specifically,we identified a total of 5481 proteins,of which 233 were differentially expressed(57 up-regulated and 176 down-regulated)in IUGR twins.Bioinformatics analysis indicates that these differentially expressed proteins(DEPs)are mainly associated with cardiovascular system development and function,organismal survival,and organismal development.Notably,34 DEPs are significantly enriched in angiogenesis,and diminished placental angiogenesis in IUGR twins has been further elaborately confirmed.Moreover,we found decreased expression of metadherin(MTDH)in the placentas of IUGR twins and demonstrated that MTDH contributes to placental angiogenesis and fetal growth in vitro.Collectively,our findings reveal the comprehensive proteomic signatures of placentas for sIUGR twins,and the DEPs identified may provide in-depth insights into the pathogenesis of placental dysfunction and subsequent impaired fetal growth.

Dietary rumen-protected L-arginine or N-carbamylglutamate attenuated fetal hepatic inflammation in undernourished ewes suffering from intrauterine growth restriction

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.

Dietary N-carbamylglutamate or L-arginine improves fetal intestinal amino acid profiles during intrauterine growth restriction in undernourished ewes

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.

Dietary dimethylglycine sodium salt supplementation alleviates redox status imbalance and intestinal dysfunction in weaned piglets with intrauterine growth restriction

There are few studies on the mechanism of redox status imbalance and intestinal dysfunction in intrauterine growth restricted(IUGR)newborn piglets.Here,we investigated the mechanism of jejunum dysfunction in weaned piglets with IUGR and the mechanism through which dimethylglycine sodium salt(DMG-Na)supplementation improving the imbalance of their redox status.In this work,a total of 10 normal birth weight(NBW)newborn piglets and 20 IUGR newborn piglets were obtained.After weaning at 21 d,they were assigned to 3 groups(n=10/group):NBW weaned piglets fed standard basal diets(NBWC);one IUGR weaned piglets fed standard basal diets(IUGRC);another IUGR weaned piglets from the same litter fed standard basal diets plus 0.1%DMG-Na(IUGRD).The piglets in these 3 groups were sacrificed at 49 d of age,and the blood and jejunum samples were collected immediately.The growth performance values in the IUGRC group were lower(P<0.05)than those in the NBWC group.Jejunum histomorphological parameters,inflammatory cytokines,and digestive enzyme activity as well as serum immunoglobulin were lower(P<0.05)in the IUGRC group than those in the NBWC group.Compared with these in the NBWC group,the redox status of serum,jejunum,and mitochondria and the expression levels of jejunum redox status-related,cell adhesion-related,and mitochondrial function-related genes and proteins were suppressed in the IUGRC group(P<0.05).However,compared with those in the IUGRC group,the growth performance values,jejunum histomorphological parameters,inflammatory cytokines,digestive enzyme activity,serum immunoglobulin,redox status of serum,jejunum,and mitochondria,and the expression levels of jejunum redox status-related,cell adhesion-related,and mitochondrial function-related genes and proteins were improved(P<0.05)in the IUGRD group.In conclusion,dietary DMG-Na supplementation alleviates redox status imbalance and intestinal dysfunction in IUGR weaned piglets mainly by activating the sirtuin 1(SIRT1)/peroxisome proliferatoractivated receptorgcoactivator-1a(PGC1a)pathway,thereby improving their unfavorable body state.

Treatment of immune dysfunction in intrauterine growth restriction piglets via supplementation with dimethylglycine sodium salt during the suckling period

This study aimed to investigate the mechanism of small intestinal immune dysfunction in intrauterine growth restriction(IUGR)newborn piglets and relieve this dysfunction via dimethylglycine sodium salt(DMG-Na)supplementation during the suckling period.Thirty sows(Duroc×[Landrace×Yorkshire])were selected,and 1 male newborn piglet with normal birth weight(NBW)and 1 male newborn piglet with IUGR were obtained from each sow.Among them,10 NBW and 10 IUGR newborns were euthanized without suckling.The other 20 NBW newborns were allocated to the group named NCON,which means NBW newborns fed a basic milk diet(BMD)(n=10),and the group named ND,which means NBW newborns fed BMD supplemented with 0.1%DMG-Na(n=10);the other 20 IUGR newborns were assigned to the group named ICON,which means IUGR newborns fed BMD(n=10),and the group named ID,which means IUGR newborns fed BMD supplemented with 0.1%DMG-Na(n=10).The newborns were fed BMD from 7 to 21 d of age and euthanized at 21 d of age to collect serum and small intestinal samples.The growth performance,small intestinal histological morphology and sub-organelle ultrastructure,serum immunoglobulin,small intestinal digestive enzyme activity,inflammatory cytokine level,and jejunum mRNA and protein expression of the toll-like receptor 4(TLR4)/nucleotide-binding oligomerization domain protein(NOD)/nuclear factor-k B(NF-k B)network deteriorated in the ICON group compared to that in the NCON group.The small intestinal histological morphology and suborganelle ultrastructure,serum immunoglobulin,small intestinal digestive enzyme activity,and inflammatory cytokine level improved(P<0.05)in the ID group compared to those in the ICON group.The jejunum mRNA and protein expression of the TLR4/NOD/NF-k B network improved(P<0.05)in the ID group compared to that in the ICON group.In conclusion,the activity of the TLR4/NOD/NF-k B pathway was inhibited in the IUGR newborns,which in turn led to their jejunum immune dysfunction and reduced their performance.By ingesting DMG-Na,the IUGR newborns activated the TLR4/NOD/NF-k B pathway,thereby improving their unfavorable body state during the suckling period.

Glucose Metabolic and Gluconeogenic Pathways Disturbance in the Intrauterine Growth Restricted Adult Male Rats

Objective To explore the molecular mechanism of type 2 diabetes in intrauterine growth restricted adult rats through determination of blood glucose and expression of gluconeogenic enzymes in liver.Methods Male intrauterine growth restriction(IUGR) offspring induced by maternal protein-malnutrition and normal controls were studied.The body weights of offspring rats were weighted from birth to 12 weeks of age.Fasting plasma glucose and insulin levels were determined by glucose oxidase method and enzyme-linked immunosorbent assay(ELISA) respectively at 1 week,8 weeks,and 12 weeks.Peroxisome proliferator-activated receptor-γ coactivator-1α(PGC-1α),phosphoenolpyruvate carboxykinase(PEPCK),and glucose-6-phosphatase(G6Pase) mRNA and protein levels in liver were measured by real time RT-PCR and Western blot in newborn rats(Week 1) and adult rats(Week 12).Results Birth weights of IUGR rats were significantly lower than those of controls until 4 weeks later,when IUGR rats caught up to controls.Between 8 and 12 weeks,the growth of IUGR rats surpassed that of controls.No significant differences were observed in blood glucose and insulin levels at newborn rats between the two groups.However,by the end of 8 weeks IUGR rats developed hyperinsulinemia and high insulin resistance index.At the age of 12 weeks,IUGR rats had mild fasting hyperglycemia.In addition,hepatic PGC-1α mRNA and protein levels as well as hepatic mRNA levels of PEPCK and G6Pase at Week 1 and Week 12 in IUGR rats were all significantly higher than those of controls(P<0.05).Conclusions As a result of intrauterine malnutrition,the expression of gluconeogenic genes is exaggerated in offspring.This change stays through adulthood and may contribute to the pathogenesis of type 2 diabetes.

Supplemental Clostridium butyricum modulates lipid metabolism by reshaping the gut microbiota composition and bile acid profile in IUGR suckling piglets

Background Intrauterine growth restriction(IUGR)can cause lipid disorders in infants and have long-term adverse effects on their growth and development.Clostridium butyricum(C.butyricum),a kind of emerging probiotics,has been reported to effectively attenuate lipid metabolism dysfunctions.Therefore,the objective of this study was to investigate the effects of C.butyricum supplementation on hepatic lipid disorders in IUGR suckling piglets.Methods Sixteen IUGR and eight normal birth weight(NBW)neonatal male piglets were used in this study.From d 3to d 24,in addition to drinking milk,the eight NBW piglets(NBW-CON group,n=8)and eight IUGR piglets(IUGR-CON group,n=8)were given 10 mL sterile saline once a day,while the remaining IUGR piglets(IUGR-CB group,n=8)were orally administered C.butyricum at a dose of 2×108colony-forming units(CFU)/kg body weight(suspended in 10 mL sterile saline)at the same frequency.Results The IUGR-CON piglets exhibited restricted growth,impaired hepatic morphology,disordered lipid metabolism,increased abundance of opportunistic pathogens and altered ileum and liver bile acid(BA)profiles.However,C.butyricum supplementation reshaped the gut microbiota of the IUGR-CB piglets,characterized by a decreased abundance of opportunistic pathogens in the ileum,including Streptococcus and Enterococcus.The decrease in these bile salt hydrolase(BSH)-producing microbes increased the content of conjugated BAs,which could be transported to the liver and function as signaling molecules to activate liver X receptorα(LXRα)and farnesoid X receptor(FXR).This activation effectively accelerated the synthesis and oxidation of fatty acids and down-regulated the total cholesterol level by decreasing the synthesis and promoting the efflux of cholesterol.As a result,the growth performance and morphological structure of the liver improved in the IUGR piglets.Conclusion These results indicate that C.butyricum supplementation in IUGR suckling piglets could decrease the abundance of BSH-producing microbes(Streptococcus and Enterococcus).This decrease altered the ileum and liver BA profiles and consequently activated the expression of hepatic LXRαand FXR.The activation of these two signaling molecules could effectively normalize the lipid metabolism and improve the growth performance of IUGR suckling piglets.

LRP6 Bidirectionally Regulates Insulin Sensitivity through Insulin Receptor and S6K Signaling in Rats with CG-IUGR

Objective Intrauterine growth restriction followed by postnatal catch-up growth(CG-IUGR)increases the risk of insulin resistance-related diseases.Low-density lipoprotein receptor-related protein 6(LRP6)plays a substantial role in glucose metabolism.However,whether LRP6 is involved in the insulin resistance of CG-IUGR is unclear.This study aimed to explore the role of LRP6 in insulin signaling in response to CG-IUGR.Methods The CG-IUGR rat model was established via a maternal gestational nutritional restriction followed by postnatal litter size reduction.The mRNA and protein expression of the components in the insulin pathway,LRP6/β-catenin and mammalian target of rapamycin(mTOR)/S6 kinase(S6K)signaling,was determined.Liver tissues were immunostained for the expression of LRP6 andβ-catenin.LRP6 was overexpressed or silenced in primary hepatocytes to explore its role in insulin signaling.Results Compared with the control rats,CG-IUGR rats showed higher homeostasis model assessment for insulin resistance(HOMA-IR)index and fasting insulin level,decreased insulin signaling,reduced mTOR/S6K/insulin receptor substrate-1(IRS-1)serine307 activity,and decreased LRP6/β-catenin in the liver tissue.The knockdown of LRP6 in hepatocytes from appropriate-for-gestational-age(AGA)rats led to reductions in insulin receptor(IR)signaling and mTOR/S6K/IRS-1 serine307 activity.In contrast,LRP6 overexpression in hepatocytes of CG-IUGR rats resulted in elevated IR signaling and mTOR/S6K/IRS-1 serine307 activity.Conclusion LRP6 regulated the insulin signaling in the CG-IUGR rats via two distinct pathways,IR and mTOR-S6K signaling.LRP6 may be a potential therapeutic target for insulin resistance in CG-IUGR individuals.

Factors controlling nutrient availability to the developing fetus in ruminants

Inadequate delivery of nutrients results in intrauterine growth restriction （IUGR）, which is a leading cause of neonatal morbidity and mortality in livestock. In ruminants, inadequate nutrition during pregnancy is often prevalent due to frequent utilization of exensive forage based grazing systems, making them highly susceptible to changes in nutrient quality and availability. Delivery of nutrients to the fetus is dependent on a number of critical factors including placental growth and development, utero-placental blood flow, nutrient availability, and placenta metabolism and transport capacity. Previous findings from our laboratory and others, highlight essential roles for amino acids and their metabolites in supporting normal fetal growth and development, as well as the critical role for amino acid transporters in nutrient delivery to the fetus. The focus of this review will be on the role of materna nutrition on placental form and function as a regulator of fetal development in ruminants.

Associations between testicular development and fetal size in the pig

Background:Impaired reproductive performance is the largest contributing factor for the removal of boars from commercial systems.Intrauterine growth restricted piglets represent 25%of the total number of piglets born and have impaired reproductive performance.This study aimed to improve the understanding of temporal changes in testicular gene expression during testes development in fetuses of different size.The lightest and closest to mean litter weight(CTMLW)male Large White×Landrace littermates were collected at gestational days(GD)45,60 and 90(n=5-6 litters/GD).Results:Testes weight and testes weight as a percentage of fetal weight were not associated with fetal size at GD60 or 90.Fetal plasma testosterone was not associated with fetal size at GD90.There was no association between fetal size and seminiferous tubule area and number,number of germ or Sertoli cells per tubule.The lightest fetuses tended to have wider seminiferous tubules compared to the CTMLW fetuses at GD90(P=0.077).The testicular expression of KI67(P≤0.01)and BAX:BCL2 ratio(P=0.058)mRNAs decreased as gestation progressed.Greater SPP1 mRNA expression was observed at GD60 when compared with GD45 and 90(P≤0.05).Lower expression of DMRT1 and SPP1(P<0.01)mRNAs was observed in testes associated with the lightest fetuses compared to the CTMLW fetuses at GD90.Conclusions:These findings provide novel insights into the expression profiles of genes associated with testicular development and function.Further,these data suggest that programming of reproductive potential in IUGR boars occurs late in gestation,providing a platform for further mechanistic investigation.

Endoplasmic reticulum stress-induced apoptosis in the development of reproduction

Proteins synthesized in the endoplasmic reticulum （ER） are properly folded with the assistance of ER chaperones. Accumulation of misfolded protein in the ER triggers an adaptive ER stress （ERS） response termed the unfolded protein response. Recent interest has focused on the possibility that the accumulation of misfolded proteins can also contribute to reproductive response, including preimplantation embryos, testicular germ cell, placenta, and unexplained intrauterine growth restriction （IUGR）. The major ERS pathway constituents are present at all stages of preimplantation development and that the activation of ERS pathways can be induced at the 8-cell, morula and blastocyst stage. This review mainly introduced the research progress of ERS induced apoptosis of reproductive cells, providing a new direction for the research of reproductive disease therapy.

Cord blood zinc status effects on pregnancy outcomes and its relation with maternal serum zinc levels:a systematic review and meta-analysis

Background The association between maternal and cord blood zinc level and pregnancy outcomes remains uncertain.The present study aims to assess whether maternal blood zinc level represents cord blood zinc level correctly.Methods In this meta-analysis,systematic search was performed in PubMed,Web of Science,and Scopus databases for relevant available English articles which included mean and standard deviation values of cord blood zinc level up to April 2019.For the assessment of the relation between cord blood zinc level and pregnancy outcomes,the pooled standard mean difference with 95%confidence interval(CI)was used and 23 studies were analyzed.Results Cumulative analysis showed that cord blood zinc level was found significantly decreased in pregnancies with complications compared with healthy pregnancy controls[REM:P=0.0007,mean difference−7.9(−12.48,−3.31)].For further analysis,maternal serum zinc level status was determined from same studies to compare with cord blood levels and subgroups were detected as“Preterm”,“Preeclampsia”,“Small for gestational age/Intrauterine growth restriction and Low birth weight”.It was observed that cord blood zinc levels in subgroup analysis were also decreased and/or tend to be decreased compared to healthy pregnancies,except for preeclampsia subgroup.Also,a correlation was seen between cord blood and maternal blood zinc level status(R=0.4365,95%CI−0.530,0.756;P=0.0351).Conclusion It was thought that cord blood zinc level might tend to decrease more than maternal serum zinc level in the pathological conditions during pregnancies.

The Controversies and Challenges in the Management of Twin Pregnancy: From the Perspective of International Federation of Gynecology and Obstetrics Guidelines

The rate of multiple pregnancy is increasing, mainly because of the widespread use of assisted reproduction techniques and families’ desire for twins. Twin pregnancy accounts for a higher risk of chromosomal abnormalities, structural malformations, and neonatal adverse events than singleton pregnancy. The presence of artery-vein anastomoses, unbalanced placenta sharing, and abnormal cord insertion in monochorionic twins is associated with twin complications such as twin-to-twin transfusion syndrome, selective intrauterine growth restriction, and twin anemia polycythemia sequence. Although many guidelines and studies have established and improved the processes about the antenatal surveillance and management of twin pregnancy, they also raise more controversies and challenges. This review aims to highlight the international consensus on the antenatal care of twin pregnancies and analyze the controversies and predicaments based on the published International Federation of Gynecology and Obstetrics guidelines and research.

Dietary N-carbamylglutamate or L-arginine supplementation improves hepatic energy status and mitochondrial function and inhibits the AMP-activated protein kinase-peroxisome proliferator- activated receptor γ coactivator-1α-transcription factor A pathway in intrauterine-growth-retarded suckling lambs

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.