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 ...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.展开更多
Fetal growth restriction(FGR),or intrauterine growth restriction(IUGR),is a complication of pregnancy where the fetus does not achieve its genetic growth potential.FGR is characterized by a pathological retardation of...Fetal growth restriction(FGR),or intrauterine growth restriction(IUGR),is a complication of pregnancy where the fetus does not achieve its genetic growth potential.FGR is characterized by a pathological retardation of intrauterine growth velocity in the curve of intrauterine growth.However,the FGR definition is still debated,and there is a lack of a uniform definition in the literature.True IUGR,compared to constitutional smallness,is a pathological condition in which the placenta fails to deliver an adequate supply of oxygen and nutrients to the developing fetus.Infants with IUGR,compared to appropriately grown gestational age infants,have a significantly higher risk of mortality and neonatal complications with long-term consequences.Several studies have demonstrated how suboptimal fetal growth leads to long-lasting physiological alterations for the developing fetus as well as for the newborn and adult in the future.The long-term effects of fetal growth retardation may be adaptations to poor oxygen and nutrient supply that are effective in the fetal period but deleterious in the long term through structural or functional alterations.Epidemiologic studies showed that FGR could be a contributing factor for adult chronic diseases including cardiovascular disease,metabolic syndrome,diabetes,respiratory diseases and impaired lung function,and chronic kidney disease.In this review we discussed pathophysiologic mechanisms of FGR-related complications and potential preventive measures for FGR.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
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
Objective: The aim of this study was to analyze homocysteine levels in maternal serum in women with pregnancies complicated by preeclampsia and/or IUGR. Patients and methods: The study was carried out on 49 pregnant p...Objective: The aim of this study was to analyze homocysteine levels in maternal serum in women with pregnancies complicated by preeclampsia and/or IUGR. Patients and methods: The study was carried out on 49 pregnant patients with normotensive pregnancies complicated by intrauterine fetal growth restriction (group IUGR), 31 patients with preeclampsia complicated by IUGR (group PRE-IUGR), and 35 preeclamptic patients with appropriate-for-gestational-age weight fetuses (group PRE). The control group consisted of 47 healthy normotensive pregnant patients with singleton uncomplicated pregnancies and with proper intrauterine fetal growth. Results: We revealed higher levels of maternal serum homocysteine in the group of pregnant patients with isolated fetal intrauterine growth restriction in comparison with the control subjects. The concentrations of homocysteine were also higher in both groups of patients with pregnancy complicated by preeclampsia with and without IUGR. The highest levels of homocysteine were observed in preeclamptic women with appropriate-for-gestational-age fetal growth. The mean values were 9.004 +/– 2.820 umol/L in the IUGR group, 10.815 +/– 3.785 umol/ L in the group PRE, 9.808 +/– 2.543 umol/L in the group PRE-IUGR and 7.639 +/– 2.728 umol/L in the control group. Conclusions: Increased levels of homocysteine are involved in pathogenesis IUGR and preeclampsia and may contribute to endothelial cells activation or dysfunction observed in these pregnancy disorders. Further studies are needed to explain these aspects in order to improve the management and therapeutic strategies for pregnancies complicated by IUGR and/or preeclampsia.展开更多
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 ...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.展开更多
基金funded by the National Natural Science Foundation of China,No.81170577
文摘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.
文摘Fetal growth restriction(FGR),or intrauterine growth restriction(IUGR),is a complication of pregnancy where the fetus does not achieve its genetic growth potential.FGR is characterized by a pathological retardation of intrauterine growth velocity in the curve of intrauterine growth.However,the FGR definition is still debated,and there is a lack of a uniform definition in the literature.True IUGR,compared to constitutional smallness,is a pathological condition in which the placenta fails to deliver an adequate supply of oxygen and nutrients to the developing fetus.Infants with IUGR,compared to appropriately grown gestational age infants,have a significantly higher risk of mortality and neonatal complications with long-term consequences.Several studies have demonstrated how suboptimal fetal growth leads to long-lasting physiological alterations for the developing fetus as well as for the newborn and adult in the future.The long-term effects of fetal growth retardation may be adaptations to poor oxygen and nutrient supply that are effective in the fetal period but deleterious in the long term through structural or functional alterations.Epidemiologic studies showed that FGR could be a contributing factor for adult chronic diseases including cardiovascular disease,metabolic syndrome,diabetes,respiratory diseases and impaired lung function,and chronic kidney disease.In this review we discussed pathophysiologic mechanisms of FGR-related complications and potential preventive measures for FGR.
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.
文摘Objective: The aim of this study was to analyze homocysteine levels in maternal serum in women with pregnancies complicated by preeclampsia and/or IUGR. Patients and methods: The study was carried out on 49 pregnant patients with normotensive pregnancies complicated by intrauterine fetal growth restriction (group IUGR), 31 patients with preeclampsia complicated by IUGR (group PRE-IUGR), and 35 preeclamptic patients with appropriate-for-gestational-age weight fetuses (group PRE). The control group consisted of 47 healthy normotensive pregnant patients with singleton uncomplicated pregnancies and with proper intrauterine fetal growth. Results: We revealed higher levels of maternal serum homocysteine in the group of pregnant patients with isolated fetal intrauterine growth restriction in comparison with the control subjects. The concentrations of homocysteine were also higher in both groups of patients with pregnancy complicated by preeclampsia with and without IUGR. The highest levels of homocysteine were observed in preeclamptic women with appropriate-for-gestational-age fetal growth. The mean values were 9.004 +/– 2.820 umol/L in the IUGR group, 10.815 +/– 3.785 umol/ L in the group PRE, 9.808 +/– 2.543 umol/L in the group PRE-IUGR and 7.639 +/– 2.728 umol/L in the control group. Conclusions: Increased levels of homocysteine are involved in pathogenesis IUGR and preeclampsia and may contribute to endothelial cells activation or dysfunction observed in these pregnancy disorders. Further studies are needed to explain these aspects in order to improve the management and therapeutic strategies for pregnancies complicated by IUGR and/or preeclampsia.
基金The Roslin Institute receives Institute Strategic Grant funding from the BBSRC(BB/J004316/1)a studentship from the University of Edinburghfunded by the National Agency for Research and Development (ANID)/Scholarship Program/DOCTORADO BECAS CHILE/2016-72170349.
文摘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.
