Background Organic acids(OA)and maternal nutritional strategies have been demonstrated to promote piglet health and development.The objective of this study was to investigate the effects of incorporating OA-preserved ...Background Organic acids(OA)and maternal nutritional strategies have been demonstrated to promote piglet health and development.The objective of this study was to investigate the effects of incorporating OA-preserved cereal grains into sow diets during late gestation and lactation,aiming to reduce the metabolic demands of lactation while optimising offspring development and growth until slaughter.The experiment compared OA-preserved wheat and barley to conventionally dried grains,focusing on sow and offspring performance,as well as their faecal microbiota during lactation.Forty sows were blocked based on parity,body weight and back fat thickness on d 100 of gestation and assigned to one of two diets:a dried grain lactation diet and a preserved grain lactation diet.Sow faecal samples were collected at farrowing for the coefficient of apparent total tract digestibility(CATTD)of nutrients and microbial analysis.Offspring faecal samples were collected on d 10 postpartum and at weaning(d 26 postpartum)for microbial analysis.Results Sow body weight,back fat changes,gestation and lactation length,total piglets born,wean-to-oestrus interval,and lactation efficiency were unaffected by sow diet(P>0.05).However,sows offered the preserved grain diet exhibited improved CATTD of dry matter,nitrogen,gross energy,and neutral detergent fibre(P<0.05).While no maternal effect was observed on offspring growth during lactation(P>0.05),pigs from sows offered the preserved grain diet showed improved growth and feed efficiency from weaning until slaughter(d 168)compared to those from sows offered the dried grain diet(P<0.05).The preserved grain diet also reduced the abundance of Proteobacteria in sow faeces at farrowing and in their offspring on d 10 postpartum,and improved piglet faecal scores throughout lactation(P=0.05).At weaning,piglets from sows offered the preserved grain diet exhibited an increased abundance of Lactobacillus and reduced abundance of Alistipes in their faeces(P<0.05).Conclusion OA-preserved grains enhanced the CATTD of nutrients in sows,promoted healthier piglet faecal scores during lactation,and improved offspring growth performance post-weaning,potentially linked to beneficial changes observed in the faecal microbiota of sows and their offspring during lactation.展开更多
Objective Electronic cigarettes(ECs)differ from traditional tobacco smoke but may contribute to cardiopulmonary remodeling.Pulmonary hypertension(PH),characterized by pulmonary artery and right ventricle remodeling,po...Objective Electronic cigarettes(ECs)differ from traditional tobacco smoke but may contribute to cardiopulmonary remodeling.Pulmonary hypertension(PH),characterized by pulmonary artery and right ventricle remodeling,poses a significant risk of mortality in infants,children,and adolescents.However,the impact of maternal EC exposure on PH development in offspring remains unclear.To address this,we established a PH rat model with maternal EC exposure.Methods Maternal EC exposure was initiated on gestation day 12 via electronic nicotine delivery systems.Offspring were administered monocrotaline(MCT)at 6 weeks of age(6-wo)to induce PH.Mechanistic experiments were conducted at 10-week-old(10-wo).Protein expression of NADPH oxidases,DNA methyltransferases,and autophagy-related markers was analyzed by Western blot.Morphological changes and the severity of PH were evaluated via hematoxylin and eosin(HE)staining and echocardiography,respectively.Furthermore,the involvement of the oxidative stress/DNA methylation/autophagy axis in response to maternal EC exposure was confirmed through a combination of ELISA,Western blot,HE staining,and echocardiography.Additionally,ATG5 mRNA expression was measured by qRT-PCR.Results Compared with control conditions,maternal EC exposure significantly worsened MCT-induced PH in male offspring.This was associated with increased oxidative stress,DNA hypomethylation,and anomalous autophagy in the offspring.In vivo treatment with chloroquine inhibited autophagy and ameliorated PH development in offspring exposed to maternal EC.Furthermore,N-acetylcysteine(NAC),an antioxidant,attenuated maternal EC exposure-induced oxidative stress,DNA hypomethylation,and excessive autophagy,thereby improving PH.DNA hypermethylation also reversed PH development,accompanied by reduced oxidative stress and suppressed autophagy.ATG5,a key regulator of autophagy,was identified as a potential therapeutic target,as its repression mitigated PH in maternal EC-exposed offspring.Conclusion Maternal EC exposure induces oxidative stress and DNA hypomethylation in offspring,leading to anomalous autophagy and exacerbation of PH development.Targeting ATG5-mediated autophagy may represent a novel therapeutic approach for improving PH outcomes in offspring exposed to maternal EC.Graphical Abstract Pregnant rats were exposed to either EC vapor or standard air from gestation day 12 until 2 days before delivery,with all offspring undergoing PH induction at 6-wo.Offspring exposed to maternal EC presented increased oxidative stress,which in turn affected DNA methylation patterns.The decreased DNA methylation in male offspring led to the activation of autophagy,exacerbating the development of PH.Treatment with ATG5 siRNA inhibited autophagy and alleviated heightened PH in male offspring with maternal EC exposure.展开更多
Inclusive fitness theory posits that altruistic behaviors,which are directed more likely towards relatives,should be favored by natural selection.However,the prevalence of alternative parenting behaviors in offspring ...Inclusive fitness theory posits that altruistic behaviors,which are directed more likely towards relatives,should be favored by natural selection.However,the prevalence of alternative parenting behaviors in offspring selection,including rejecting their own offspring and accepting the offspring of others,remains poorly understood within the context of parental care evolution.In order to investigate the factors that prompt the occurrence of alternative parenting behaviors,we designed a series of experiments in the Azure-winged Magpie(Cyanopica cyanus).By manipulating the nest spatial position or offspring age/number and parent-offspring familiarity,we addressed how parents provided parental care for the manipulated offspring.In the nest resettlement experiment,the probability of parents rejecting their own offspring significantly increased with nest-moving distances while decreased with offspring ages.In the cross-fostering experiments,the probability of parents provisioning unrelated young significantly decreased with the age difference between cross-fostered chicks.In the nest duplication experiments,where parents were given a choice between familiar offspring and unfamiliar unrelated chicks or between unfamiliar offspring and familiar unrelated chicks,the probability of both alternative parenting behaviors was significantly influenced by the time when parental association with their offspring was deprived.We conclude that as offspring phenotypic traits become individualized and fixed at a special developmental stage,parents gradually acquire the capacity for offspring recognition by associating with them.Any factors that disrupt parent-offspring association or introduce unrelated young into the nest prior to this critical timeline can result in the occurrence of alternative parenting behaviors.展开更多
Nicotine,ethanol,and caffeine are the most common exogenous substances in the men’s living environment,but their effects on the cartilage quality in the father and offspring have not been reported.According to the av...Nicotine,ethanol,and caffeine are the most common exogenous substances in the men’s living environment,but their effects on the cartilage quality in the father and offspring have not been reported.According to the average daily intake of adult men,we constructed a male rat model of paternal mixed exposure(PME)to low-dose nicotine(0.1 mg/(kg·day)),ethanol(0.5 g/(kg·day)),and caffeine(7.5 mg/(kg·day))for 8 weeks.Then,the male rats mated with normal female rats to obtain offspring.The results showed that PME reduced the cartilage quality of paternal and offspring rats.Among them,the paternal cartilage was damaged by enhancing matrix degradation,while the offspring cartilage was damaged by reducing matrix synthesis.The cartilage damage in male offspring rats was more evident than in female offspring.It was further confirmed that differential GC regulation mechanisms were the main reasons for the intergenerational differential damage of paternal/offspring cartilage quality caused by PME.In addition,the androgen receptor(AR)and estrogen receptor beta(ERβ)mediated the sex difference of PME-induced fetal cartilage dysplasia by affecting the binding degree of GR/P300.This study provided a theoretical and experimental basis for guiding male healthy lifestyle and exploring early prevention and treatment strategies for paternal diseases.展开更多
Theincreasing prevalence of gestational diabetesmellitus(GDM)is associated with an array of pregnancy complications and enduring health challenges in bothmothers and their offspring.Studies have indicated that exposur...Theincreasing prevalence of gestational diabetesmellitus(GDM)is associated with an array of pregnancy complications and enduring health challenges in bothmothers and their offspring.Studies have indicated that exposure to the intrauterine environment can prompt adaptations in the offspring,thereby programming transgenerational inheritance.Physical activity during pregnancy,as a non-pharmacological intervention,mitigates metabolic risks through epigenetic modifications,mediating placental adaptations,the action of exercise factors,and gut microbiota.Here,we provide a review summarizing how regular exercise can reduce the risk of GDM and positively influence pregnancy outcomes.It also discusses the exercise-induced reduction in obesity,insulin resistance,and fatty liver disease in the offspring of GDM,outlining the mechanisms that underpin these health benefits.This review underscores the importance of exercise in safeguarding the health of GDM mothers and their offspring.展开更多
Gestational diabetes mellitus(GDM)is a pregnancy-related complication characterized by abnormal glucose metabolism in pregnant women and has an important impact on fetal development.As a bridge between the mother and ...Gestational diabetes mellitus(GDM)is a pregnancy-related complication characterized by abnormal glucose metabolism in pregnant women and has an important impact on fetal development.As a bridge between the mother and the fetus,the placenta has nutrient transport functions,endocrine functions,etc.,and can regulate placental nutrient transport and fetal growth and development according to maternal metabolic status.Only by means of placental transmission can changes in maternal hyperglycemia affect the fetus.There are many reports on the placental pathophysiological changes associated with GDM,the impacts of GDM on the growth and development of offspring,and the prevalence of GDM in offspring after birth.Placental epigenetic changes in GDM are involved in the programming of fetal development and are involved in the pathogenesis of later chronic diseases.This paper summarizes the effects of changes in placental nutrient transport function and hormone secretion levels due to maternal hyperglycemia and hyperinsulinemia on the development of offspring as well as the participation of changes in placental epigenetic modifications due to maternal hyperglycemia in intrauterine fetal programming to promote a comprehensive understanding of the impacts of placental epigenetic modifications on the development of offspring from patients with GDM.展开更多
BACKGROUND Prolonged fetal exposure to hyperglycemia may increase the risk of developing abnormal glucose metabolism and type-2 diabetes during childhood,adolescence,and adulthood;however,the mechanisms by which gesta...BACKGROUND Prolonged fetal exposure to hyperglycemia may increase the risk of developing abnormal glucose metabolism and type-2 diabetes during childhood,adolescence,and adulthood;however,the mechanisms by which gestational diabetes mellitus(GDM)predisposes offspring to metabolic disorders remain unknown.AIM To quantify the nerve axons,macrophages,and vasculature in the pancreas from adult offspring born from mouse dams with GDM.METHODS GDM was induced by i.p.administration of streptozotocin(STZ)in ICR mouse dams.At 12 wk old,fasting blood glucose levels were determined in offspring.At 15 wk old,female offspring born from dams with and without GDM were sacrificed and pancreata were processed for immunohistochemistry.We quantified the density of sensory[calcitonin gene-related peptide(CGRP)]and tyrosine hydroxylase(TH)axons,blood vessels(endomucin),and macro-phages(CD68)in the splenic pancreas using confocal microscopy.RESULTS Offspring mice born from STZ-treated dams had similar body weight and blood glucose values compared to offspring born from vehicle-treated dams.However,the density of CGRP+and TH+axons,endomucin+blood vessels,and CD68+macrophages in the exocrine pancreas was significantly greater in offspring from mothers with GDM vs control offspring.Likewise,the microvasculature in the islets was significantly greater,but not the number of macrophages within the islets of offspring born from dams with GDM compared to control mice.CONCLUSION GDM induces neuronal,vascular,and inflammatory changes in the pancreas of adult progeny,which may partially explain the higher propensity for offspring of mothers with GDM to develop metabolic diseases.展开更多
BACKGROUND Gestational diabetes mellitus(GDM)women require prenatal care to minimize short-and long-term complications.The mechanism by which exercise during pregnancy affects organ development and whether glucose tra...BACKGROUND Gestational diabetes mellitus(GDM)women require prenatal care to minimize short-and long-term complications.The mechanism by which exercise during pregnancy affects organ development and whether glucose transporter(GLUT)1 plays a role in GDM offspring organ development remains unknown.AIM To determine the effect of exercise during pregnancy on the cardiac,hepatic and renal development of GDM mother’s offspring.METHODS Placenta samples were collected from humans and mice.GDM mouse models were created using streptozotocin along with a GDM with exercise group.The hearts,livers and kidneys of 3-and 8-week-old offspring were collected for body composition analysis and staining.The effects of high glucose levels and hypoxia were investigated using HTR8/SVneo.Transwell and wound-healing assays were performed to assess cell migration.Immunofluorescence accompanied with TUNEL and Ki67 staining was used to explore apoptosis and proliferation.RESULTS Exercise during pregnancy downregulated the GLUT1 and hypoxia inducible factor-1αexpression in placenta from individuals with GDM.Cobalt chloride induced hypoxia and high glucose levels also significantly decreased migration and apoptosis of HTR8/SVneo cells.In addition,exercise reduced inflammatory cell infiltration in the liver and decreased the tubular vacuolar area in the kidneys of offspring.CONCLUSION GDM affects the growth and development of organs in offspring.Exercise during pregnancy can reverse adverse effects of GDM on the development of the heart,liver,and kidney in offspring.展开更多
Maternal sleep deprivation(MSD)has emerged as a significant public health concern,yet its effects on offspring metabolism remain poorly understood.This study investigated the metabolomic implications of MSD on offspri...Maternal sleep deprivation(MSD)has emerged as a significant public health concern,yet its effects on offspring metabolism remain poorly understood.This study investigated the metabolomic implications of MSD on offspring cognitive development,with a particular focus on alterations in glutamate metabolism.Pregnant rats were subjected to sleep deprivation during late gestation.Plasma and brain samples from their offspring were collected at different postnatal days(P1,P7,P14,and P56)and analyzed using untargeted metabolomics with liquid chromatography-mass spectrometry.Metabolomic analysis revealed significant differences in various amino acids,including L-glutamate,L-phenylalanine,L-tyrosine,and L-tryptophan,which are crucial for cognitive function.Subsequent differential analysis and partial least squares discriminant analysis(sPLS-DA)demonstrated a gradual reduction in these metabolic differences in the brain as the offspring underwent growth and development.KEGG pathway analysis revealed differential regulation of several pathways,including alanine,aspartate,and glutamate metabolism,glutathione metabolism,arginine biosynthesis,aminoacyl-tRNA biosynthesis,histidine metabolism,and taurine and hypotaurine metabolism,at different developmental stages.Mantel and Spearman analyses indicated that the observed changes in metabolites in MSD progeny may be related to various gut microbes,Ruminococcus_1,Ruminococcaceae_UCG-005,and Eubacterium_coprostanoligenes_group.Biochemical assays further demonstrated developmental changes in the L-glutamate metabolic pathway.Collectively,these findings suggest that MSD not only affects maternal wellbeing but also has enduring metabolic consequences for offspring,particularly impacting pathways linked to cognitive function.This highlights the importance of addressing maternal sleep health to mitigate potential long-term consequences for offspring.展开更多
基金funded by the Science Foundation Ireland(BiOrbic,Dublin,Ireland)and Adesco Nutricines(Dungarvan,Waterford,Ireland)under grant number 16/RC/3889。
文摘Background Organic acids(OA)and maternal nutritional strategies have been demonstrated to promote piglet health and development.The objective of this study was to investigate the effects of incorporating OA-preserved cereal grains into sow diets during late gestation and lactation,aiming to reduce the metabolic demands of lactation while optimising offspring development and growth until slaughter.The experiment compared OA-preserved wheat and barley to conventionally dried grains,focusing on sow and offspring performance,as well as their faecal microbiota during lactation.Forty sows were blocked based on parity,body weight and back fat thickness on d 100 of gestation and assigned to one of two diets:a dried grain lactation diet and a preserved grain lactation diet.Sow faecal samples were collected at farrowing for the coefficient of apparent total tract digestibility(CATTD)of nutrients and microbial analysis.Offspring faecal samples were collected on d 10 postpartum and at weaning(d 26 postpartum)for microbial analysis.Results Sow body weight,back fat changes,gestation and lactation length,total piglets born,wean-to-oestrus interval,and lactation efficiency were unaffected by sow diet(P>0.05).However,sows offered the preserved grain diet exhibited improved CATTD of dry matter,nitrogen,gross energy,and neutral detergent fibre(P<0.05).While no maternal effect was observed on offspring growth during lactation(P>0.05),pigs from sows offered the preserved grain diet showed improved growth and feed efficiency from weaning until slaughter(d 168)compared to those from sows offered the dried grain diet(P<0.05).The preserved grain diet also reduced the abundance of Proteobacteria in sow faeces at farrowing and in their offspring on d 10 postpartum,and improved piglet faecal scores throughout lactation(P=0.05).At weaning,piglets from sows offered the preserved grain diet exhibited an increased abundance of Lactobacillus and reduced abundance of Alistipes in their faeces(P<0.05).Conclusion OA-preserved grains enhanced the CATTD of nutrients in sows,promoted healthier piglet faecal scores during lactation,and improved offspring growth performance post-weaning,potentially linked to beneficial changes observed in the faecal microbiota of sows and their offspring during lactation.
基金supported by National Natural Science Foundation of China(No.82300268)Guangzhou Municipal Science and Technology Project(No.2023B03J1255).
文摘Objective Electronic cigarettes(ECs)differ from traditional tobacco smoke but may contribute to cardiopulmonary remodeling.Pulmonary hypertension(PH),characterized by pulmonary artery and right ventricle remodeling,poses a significant risk of mortality in infants,children,and adolescents.However,the impact of maternal EC exposure on PH development in offspring remains unclear.To address this,we established a PH rat model with maternal EC exposure.Methods Maternal EC exposure was initiated on gestation day 12 via electronic nicotine delivery systems.Offspring were administered monocrotaline(MCT)at 6 weeks of age(6-wo)to induce PH.Mechanistic experiments were conducted at 10-week-old(10-wo).Protein expression of NADPH oxidases,DNA methyltransferases,and autophagy-related markers was analyzed by Western blot.Morphological changes and the severity of PH were evaluated via hematoxylin and eosin(HE)staining and echocardiography,respectively.Furthermore,the involvement of the oxidative stress/DNA methylation/autophagy axis in response to maternal EC exposure was confirmed through a combination of ELISA,Western blot,HE staining,and echocardiography.Additionally,ATG5 mRNA expression was measured by qRT-PCR.Results Compared with control conditions,maternal EC exposure significantly worsened MCT-induced PH in male offspring.This was associated with increased oxidative stress,DNA hypomethylation,and anomalous autophagy in the offspring.In vivo treatment with chloroquine inhibited autophagy and ameliorated PH development in offspring exposed to maternal EC.Furthermore,N-acetylcysteine(NAC),an antioxidant,attenuated maternal EC exposure-induced oxidative stress,DNA hypomethylation,and excessive autophagy,thereby improving PH.DNA hypermethylation also reversed PH development,accompanied by reduced oxidative stress and suppressed autophagy.ATG5,a key regulator of autophagy,was identified as a potential therapeutic target,as its repression mitigated PH in maternal EC-exposed offspring.Conclusion Maternal EC exposure induces oxidative stress and DNA hypomethylation in offspring,leading to anomalous autophagy and exacerbation of PH development.Targeting ATG5-mediated autophagy may represent a novel therapeutic approach for improving PH outcomes in offspring exposed to maternal EC.Graphical Abstract Pregnant rats were exposed to either EC vapor or standard air from gestation day 12 until 2 days before delivery,with all offspring undergoing PH induction at 6-wo.Offspring exposed to maternal EC presented increased oxidative stress,which in turn affected DNA methylation patterns.The decreased DNA methylation in male offspring led to the activation of autophagy,exacerbating the development of PH.Treatment with ATG5 siRNA inhibited autophagy and alleviated heightened PH in male offspring with maternal EC exposure.
基金provided by the National Natural Sciences Foundation of China (Grant 32071491,31772465,31672299,31572271,and 32260128)。
文摘Inclusive fitness theory posits that altruistic behaviors,which are directed more likely towards relatives,should be favored by natural selection.However,the prevalence of alternative parenting behaviors in offspring selection,including rejecting their own offspring and accepting the offspring of others,remains poorly understood within the context of parental care evolution.In order to investigate the factors that prompt the occurrence of alternative parenting behaviors,we designed a series of experiments in the Azure-winged Magpie(Cyanopica cyanus).By manipulating the nest spatial position or offspring age/number and parent-offspring familiarity,we addressed how parents provided parental care for the manipulated offspring.In the nest resettlement experiment,the probability of parents rejecting their own offspring significantly increased with nest-moving distances while decreased with offspring ages.In the cross-fostering experiments,the probability of parents provisioning unrelated young significantly decreased with the age difference between cross-fostered chicks.In the nest duplication experiments,where parents were given a choice between familiar offspring and unfamiliar unrelated chicks or between unfamiliar offspring and familiar unrelated chicks,the probability of both alternative parenting behaviors was significantly influenced by the time when parental association with their offspring was deprived.We conclude that as offspring phenotypic traits become individualized and fixed at a special developmental stage,parents gradually acquire the capacity for offspring recognition by associating with them.Any factors that disrupt parent-offspring association or introduce unrelated young into the nest prior to this critical timeline can result in the occurrence of alternative parenting behaviors.
基金supported by the National Natural Science Foundation of China(U22A20362,U23A20407,82030111,82104301)Hubei Province’s Outstanding Medical Academic Leader program.
文摘Nicotine,ethanol,and caffeine are the most common exogenous substances in the men’s living environment,but their effects on the cartilage quality in the father and offspring have not been reported.According to the average daily intake of adult men,we constructed a male rat model of paternal mixed exposure(PME)to low-dose nicotine(0.1 mg/(kg·day)),ethanol(0.5 g/(kg·day)),and caffeine(7.5 mg/(kg·day))for 8 weeks.Then,the male rats mated with normal female rats to obtain offspring.The results showed that PME reduced the cartilage quality of paternal and offspring rats.Among them,the paternal cartilage was damaged by enhancing matrix degradation,while the offspring cartilage was damaged by reducing matrix synthesis.The cartilage damage in male offspring rats was more evident than in female offspring.It was further confirmed that differential GC regulation mechanisms were the main reasons for the intergenerational differential damage of paternal/offspring cartilage quality caused by PME.In addition,the androgen receptor(AR)and estrogen receptor beta(ERβ)mediated the sex difference of PME-induced fetal cartilage dysplasia by affecting the binding degree of GR/P300.This study provided a theoretical and experimental basis for guiding male healthy lifestyle and exploring early prevention and treatment strategies for paternal diseases.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82401994)the Top Medical Expert Team of the Wuxi Taihu Talent Plan(Grant Nos.DJTD202106,GDTD202105)+1 种基金the Medical Key Discipline Program of theWuxi Health Commission(Grant Nos.ZDXK2021007,CXTD2021005)Top Talent Support Program for Young and Middle-Aged People of Wuxi Health Committee(Grant No.HB2023079).
文摘Theincreasing prevalence of gestational diabetesmellitus(GDM)is associated with an array of pregnancy complications and enduring health challenges in bothmothers and their offspring.Studies have indicated that exposure to the intrauterine environment can prompt adaptations in the offspring,thereby programming transgenerational inheritance.Physical activity during pregnancy,as a non-pharmacological intervention,mitigates metabolic risks through epigenetic modifications,mediating placental adaptations,the action of exercise factors,and gut microbiota.Here,we provide a review summarizing how regular exercise can reduce the risk of GDM and positively influence pregnancy outcomes.It also discusses the exercise-induced reduction in obesity,insulin resistance,and fatty liver disease in the offspring of GDM,outlining the mechanisms that underpin these health benefits.This review underscores the importance of exercise in safeguarding the health of GDM mothers and their offspring.
文摘Gestational diabetes mellitus(GDM)is a pregnancy-related complication characterized by abnormal glucose metabolism in pregnant women and has an important impact on fetal development.As a bridge between the mother and the fetus,the placenta has nutrient transport functions,endocrine functions,etc.,and can regulate placental nutrient transport and fetal growth and development according to maternal metabolic status.Only by means of placental transmission can changes in maternal hyperglycemia affect the fetus.There are many reports on the placental pathophysiological changes associated with GDM,the impacts of GDM on the growth and development of offspring,and the prevalence of GDM in offspring after birth.Placental epigenetic changes in GDM are involved in the programming of fetal development and are involved in the pathogenesis of later chronic diseases.This paper summarizes the effects of changes in placental nutrient transport function and hormone secretion levels due to maternal hyperglycemia and hyperinsulinemia on the development of offspring as well as the participation of changes in placental epigenetic modifications due to maternal hyperglycemia in intrauterine fetal programming to promote a comprehensive understanding of the impacts of placental epigenetic modifications on the development of offspring from patients with GDM.
基金Supported by the National Council for Humanities,Science and Technology of Mexico CONAHCyT,No.CB/2017-2018/A1-S-27869.
文摘BACKGROUND Prolonged fetal exposure to hyperglycemia may increase the risk of developing abnormal glucose metabolism and type-2 diabetes during childhood,adolescence,and adulthood;however,the mechanisms by which gestational diabetes mellitus(GDM)predisposes offspring to metabolic disorders remain unknown.AIM To quantify the nerve axons,macrophages,and vasculature in the pancreas from adult offspring born from mouse dams with GDM.METHODS GDM was induced by i.p.administration of streptozotocin(STZ)in ICR mouse dams.At 12 wk old,fasting blood glucose levels were determined in offspring.At 15 wk old,female offspring born from dams with and without GDM were sacrificed and pancreata were processed for immunohistochemistry.We quantified the density of sensory[calcitonin gene-related peptide(CGRP)]and tyrosine hydroxylase(TH)axons,blood vessels(endomucin),and macro-phages(CD68)in the splenic pancreas using confocal microscopy.RESULTS Offspring mice born from STZ-treated dams had similar body weight and blood glucose values compared to offspring born from vehicle-treated dams.However,the density of CGRP+and TH+axons,endomucin+blood vessels,and CD68+macrophages in the exocrine pancreas was significantly greater in offspring from mothers with GDM vs control offspring.Likewise,the microvasculature in the islets was significantly greater,but not the number of macrophages within the islets of offspring born from dams with GDM compared to control mice.CONCLUSION GDM induces neuronal,vascular,and inflammatory changes in the pancreas of adult progeny,which may partially explain the higher propensity for offspring of mothers with GDM to develop metabolic diseases.
基金Supported by Key R and D Program of Zhejiang Province,No.2022C03058Medical and Health Technology Program of Zhejiang Province,No.WKJ-ZJ-2324and 4+X Clinical Research Project of Women's Hospital,School of Medicine,Zhejiang University,No.ZDFY2022-4XB101.
文摘BACKGROUND Gestational diabetes mellitus(GDM)women require prenatal care to minimize short-and long-term complications.The mechanism by which exercise during pregnancy affects organ development and whether glucose transporter(GLUT)1 plays a role in GDM offspring organ development remains unknown.AIM To determine the effect of exercise during pregnancy on the cardiac,hepatic and renal development of GDM mother’s offspring.METHODS Placenta samples were collected from humans and mice.GDM mouse models were created using streptozotocin along with a GDM with exercise group.The hearts,livers and kidneys of 3-and 8-week-old offspring were collected for body composition analysis and staining.The effects of high glucose levels and hypoxia were investigated using HTR8/SVneo.Transwell and wound-healing assays were performed to assess cell migration.Immunofluorescence accompanied with TUNEL and Ki67 staining was used to explore apoptosis and proliferation.RESULTS Exercise during pregnancy downregulated the GLUT1 and hypoxia inducible factor-1αexpression in placenta from individuals with GDM.Cobalt chloride induced hypoxia and high glucose levels also significantly decreased migration and apoptosis of HTR8/SVneo cells.In addition,exercise reduced inflammatory cell infiltration in the liver and decreased the tubular vacuolar area in the kidneys of offspring.CONCLUSION GDM affects the growth and development of organs in offspring.Exercise during pregnancy can reverse adverse effects of GDM on the development of the heart,liver,and kidney in offspring.
基金supported by the National Natural Science Foundation of China(32371030,82071395)Natural Science Foundation of Chongqing(CSTB2024NSCQ-LZX0008)+1 种基金Science and Technology Research Program of Chongqing Municipal Education Commission(KJQN202300424)CQMU Program for Youth Innovation in Future Medicine(W0044)。
文摘Maternal sleep deprivation(MSD)has emerged as a significant public health concern,yet its effects on offspring metabolism remain poorly understood.This study investigated the metabolomic implications of MSD on offspring cognitive development,with a particular focus on alterations in glutamate metabolism.Pregnant rats were subjected to sleep deprivation during late gestation.Plasma and brain samples from their offspring were collected at different postnatal days(P1,P7,P14,and P56)and analyzed using untargeted metabolomics with liquid chromatography-mass spectrometry.Metabolomic analysis revealed significant differences in various amino acids,including L-glutamate,L-phenylalanine,L-tyrosine,and L-tryptophan,which are crucial for cognitive function.Subsequent differential analysis and partial least squares discriminant analysis(sPLS-DA)demonstrated a gradual reduction in these metabolic differences in the brain as the offspring underwent growth and development.KEGG pathway analysis revealed differential regulation of several pathways,including alanine,aspartate,and glutamate metabolism,glutathione metabolism,arginine biosynthesis,aminoacyl-tRNA biosynthesis,histidine metabolism,and taurine and hypotaurine metabolism,at different developmental stages.Mantel and Spearman analyses indicated that the observed changes in metabolites in MSD progeny may be related to various gut microbes,Ruminococcus_1,Ruminococcaceae_UCG-005,and Eubacterium_coprostanoligenes_group.Biochemical assays further demonstrated developmental changes in the L-glutamate metabolic pathway.Collectively,these findings suggest that MSD not only affects maternal wellbeing but also has enduring metabolic consequences for offspring,particularly impacting pathways linked to cognitive function.This highlights the importance of addressing maternal sleep health to mitigate potential long-term consequences for offspring.
