Perfluorooctane sulfonate （PFOS） is a class of stable organic compounds with wide industrial,commercial, and consumer applications, such as in textiles, paper, pesticides, and shampoos;. It is readily absorbed, but ...Perfluorooctane sulfonate （PFOS） is a class of stable organic compounds with wide industrial,commercial, and consumer applications, such as in textiles, paper, pesticides, and shampoos;. It is readily absorbed, but poorly eliminated, with the elimination half-life of approximately 5 years;.Hence, there have been concerns regarding its potential damage to human health. Some studies展开更多
Objective: Kratom is widely available and literature exploring the effects of prenatal kratom exposure is lacking. This study aims to report a validated method for the detection of mitragynine in the umbilical cord an...Objective: Kratom is widely available and literature exploring the effects of prenatal kratom exposure is lacking. This study aims to report a validated method for the detection of mitragynine in the umbilical cord and report our observations for specimens received at a national commercial reference laboratory. Study Design: Assays were validated according to the recommendations of ANSI/ASB. A retrospective evaluation of records at a national reference laboratory was conducted to determine prevalence and co-exposure to other substances of abuse. Result: Mitragynine was detected in 19 of 4456 specimens (0.43%) with concentrations ranging from 4 to >50 ng/g. Thirteen (13) of these specimens were positive for only mitragynine while the other 6 were also positive for either marijuana or opiates. Conclusion: Umbilical cord is a suitable specimen type for the surveillance of maternal kratom use and can be used to identify exposed neonates for further investigations into short- or long- term health consequences.展开更多
Background: Prenatal exposure to fentanyl may lead to Neonatal Abstinence Syndrome (NAS), a constellation of symptoms observed when newborns begin withdrawing from addictive substances such as opioids. The use of umbi...Background: Prenatal exposure to fentanyl may lead to Neonatal Abstinence Syndrome (NAS), a constellation of symptoms observed when newborns begin withdrawing from addictive substances such as opioids. The use of umbilical cord tissue segments (UC) for newborn toxicology has been increasing due to its apparent long detection window, sensitivity, and ease of collection. However, very little has been reported in the literature concerning the prevalence of in utero exposure to fentanyl and co-exposure with other commonly abused substances. Specific aim: The specific aims of this retrospective study are twofold. We will report prevalence of neonatal exposure to fentanyl for a nationwide high-risk population using UC submitted to a national reference laboratory for routine forensic toxicology analysis and the co-exposure patterns observed for these fentanyl-exposed neonates. Methods: A secondary analysis was performed using historical data for UC received between January 1, 2020 and December 31, 2020 for routine forensic toxicology analysis. Results: During the study period, our laboratory received 23,104 UC for analysis and 9667 (41.8%) of those UC were positive for at least one drug. The prevalence of fentanyl detection was 1.9% (n = 429). Of these 429 specimens there were 407 UC where both fentanyl and norfentanyl were detected. There were 14 UC where only fentanyl was detected and 8 UC where only norfentanyl was detected. When detected, the median concentrations of fentanyl and norfentanyl were 4029 pg/g (IQR: 1696, 9230 pg/g) and 10,756 pg/mg (IQR: 3925, 25,288 pg/g), respectively. Of the 429 positive fentanyl and/or norfentanyl UC, 33 (7.7%) were only positive for fentanyl and/or norfentanyl. Of the 396 polypositive UC, morphine was the highest co-exposure with 243 UC (56.6%) being positive for both fentanyls and morphine. The second most prevalent co-exposure observed was methamphetamine/amphetamine (n = 173;40.3%) followed by cannabinoids (n = 113;26.3%) and benzoylecgonine (cocaine metabolite;n = 106;24.7%). Conclusions: Nonmedical use of fentanyl is an alarming trend in this country including this maternal demographic reported here. Fentanyl was typically found with other commonly abused substances.展开更多
Background Prenatal bisphenol exposure has been reported to be associated with lower birth weight and obesity-related indicators in early childhood.These findings warrant an investigation of the relationship between p...Background Prenatal bisphenol exposure has been reported to be associated with lower birth weight and obesity-related indicators in early childhood.These findings warrant an investigation of the relationship between prenatal bisphenol exposure and the dynamic growth of offspring.This study aimed to evaluate the relationship of maternal bisphenol concentration in urine with the body mass index(BMI)growth trajectory of children aged up to two years and to identify the critical exposure periods.Methods A total of 826 mother–offspring pairs were recruited from Wuhan Children’s Hospital between November 2013 and March 2015.Maternal urine samples collected during the first,second,and third trimesters were analyzed for bisphenol A(BPA),bisphenol S,and bisphenol F(BPF)concentrations.Measurements of length and weight were taken at 0,1,3,6,8,12,18,and 24 months.Children's BMI was standardized using the World Health Organization reference,and group-based trajectory modeling was used to identify BMI growth trajectories.The associations between prenatal bisphenol exposure and BMI growth trajectory patterns were assessed using multinomial logistic regression models.Results The BMI growth trajectories of the 826 children were categorized into four patterns:low-stable(n=134,16.2%),low-increasing(n=142,17.2%),moderate-stable(n=350,42.4%),and moderate-increasing(n=200,24.2%).After adjusting for potential confounders,we observed that prenatal exposure to BPA during the second trimester[odds ratio(OR)=2.20,95%confidence interval(CI)=1.09–4.43]and BPF during the third trimester(OR=3.28,95%CI=1.55–6.95)at the highest quartile concentration were associated with an increased likelihood of the low-increasing BMI trajectory.Furthermore,in the subgroup analysis by infant sex,the positive association between the highest quartile of prenatal average urinary BPF concentration during the whole pregnancy and the low-increasing BMI trajectory was found only in girls(OR=2.82,95%CI=1.04–7.68).Conclusion Our study findings suggest that prenatal exposure to BPA and BPF(a commonly used substitute for BPA)is associated with BMI growth trajectories in offspring during the first two years,increasing the likelihood of the low-increasing pattern.展开更多
Amoxicillin,a widely used antibiotic in human and veterinary pharmaceuticals,is now considered as an“emerging contaminant”because it exists widespreadly in the environment and brings a series of adverse outcomes.Cur...Amoxicillin,a widely used antibiotic in human and veterinary pharmaceuticals,is now considered as an“emerging contaminant”because it exists widespreadly in the environment and brings a series of adverse outcomes.Currently,systematic studies about the developmental toxicity of amoxicillin are still lacking.We explored the potential effects of amoxicillin exposure on pregnancy outcomes,maternal/fetal serum phenotypes,and fetal multiple organ development in mice,at different doses(75,150,300 mg/(kg·day))during late-pregnancy,or at a dose of 300 mg/(kg·day)during different stages(mid-/latepregnancy)and courses(single-/multi-course).Results showed that prenatal amoxicillin exposure(PAmE)had no significant infuence on the body weights of dams,but it could inhibit the physical development and reduce the survival rate of fetuses,especially during the midpregnancy.Meanwhile,PAmE altered multiple maternal/fetal serum phenotypes,especially in fetuses.Fetal multi-organ function results showed that PAmE inhibited testicular/adrenal steroid synthesis,long bone/cartilage and hippocampal development,and enhanced ovarian steroid synthesis and hepatic glycogenesis/lipogenesis,and the order of severity might be gonad(testis,ovary)>liver>others.Further analysis found that PAmE-induced multiorgan developmental and functional alterations had differences in stages,courses and fetal gender,and the most obvious changes might be in high-dose,late-pregnancy and multicourse,but there was no typical rule of a dose-response relationship.In conclusion,this study confirmed that PAmE could cause abnormal development and multi-organ function alterations,which deepens our understanding of the risk of PAmE and provides an experimental basis for further exploration of the long-term harm.展开更多
Prenatal alcohol exposure disrupts the development of normal fetal respiratory function, but whether it perturbs respiratory rhythmical discharge activity is unclear. Furthermore, it is unknown whether the 5-hydroxytr...Prenatal alcohol exposure disrupts the development of normal fetal respiratory function, but whether it perturbs respiratory rhythmical discharge activity is unclear. Furthermore, it is unknown whether the 5-hydroxytryptamine 2A receptor（5-HT2AR） is involved in the effects of prenatal alcohol exposure. In the present study, pregnant female rats received drinking water containing alcohol at concentrations of 0%, 1%, 2%, 4%, 8% or 10%（v/v） throughout the gestation period. Slices of the medulla from 2-day-old neonatal rats were obtained to record respiratory rhythmical discharge activity. 5-HT2 AR protein and m RNA levels in the pre-B？tzinger complex of the respiratory center were measured by western blot analysis and quantitative RT-PCR, respectively. Compared with the 0% alcohol group, respiratory rhythmical discharge activity in medullary slices in the 4%, 8% and 10% alcohol groups was decreased, and the reduction was greatest in the 8% alcohol group. Respiratory rhythmical discharge activity in the 10% alcohol group was irregular. Thus, 8% was the most effective alcohol concentration at attenuating respiratory rhythmical discharge activity. These findings suggest that prenatal alcohol exposure attenuates respiratory rhythmical discharge activity in neonatal rats by downregulating 5-HT2 AR protein and m RNA levels.展开更多
Prednisone is a synthetic glucocorticoid that is commonly used in both human and veterinary medication.Now,it is also recognized as an emerging environmental contaminant.Pregnantwomenmay be exposed to prednisone activ...Prednisone is a synthetic glucocorticoid that is commonly used in both human and veterinary medication.Now,it is also recognized as an emerging environmental contaminant.Pregnantwomenmay be exposed to prednisone actively or passively throughmultiple pathways and cause developmental toxicity to the fetus.However,the impact of prenatal prednisone exposure(PPE)on fetal kidney development remains unclear.In this study,pregnant mice were administered prednisone intragastrically during full-term pregnancy with different doses(0.25,0.5,or 1 mg/(kg·day)),or at the dose of 1 mg/(kg·day)in different gestational days(GD)(GD0-9,GD10-18,or GD0-18).The pregnant mice were euthanized on GD18.HE staining revealed fetal kidney dysplasia,with an enlarged glomerular Bowman’s capsule space and a reduced capillary network in the PPE groups.The expression of the podocyte and the mesangial cell marker genes was significantly reduced in the PPE groups.However,overall gene expression in renal tubules and collecting ducts were markedly increased.All of the above effects were more pronounced in high-dose,full-term pregnancy,and female fetuses.Studies on the mechanism of the female fetal kidney have revealed that PPE reduced the expression of Six2,increased the expression of Hnf1β,Hnf4α,and Wnt9b,and inhibited the expression of glial cell line-derived neurotrophic factor(GDNF)and Notch signaling pathways.In conclusion,this study demonstrated that there is a sex difference in the developmental toxicity of PPE to the fetal kidney,and the time effect is manifested as full-term pregnancy>early pregnancy>mid-late pregnancy.展开更多
Prenatal caffeine exposure(PCE)leads to intrauterine growth retardation and altered glucose homeostasis after birth,but the underlying mechanism remains unclear.This study aims to investigate the alteration of pancrea...Prenatal caffeine exposure(PCE)leads to intrauterine growth retardation and altered glucose homeostasis after birth,but the underlying mechanism remains unclear.This study aims to investigate the alteration of pancreatic development and insulin biosynthesis in the PCE female offspring and explore the intrauterine programming mechanism.Pregnant rats were orally treated with 120 mg/(kg·day)of caffeine from gestational day(GD)9 to 20.Results showed that fetal pancreaticβ-cells in the PCE group exhibited reduced mass and impaired insulin synthesis function,as evidenced by decreased expression of developmental and functional genes and reduced pancreatic insulin content.At postnatal week(PW)12,the PCE offspring exhibited glucose intolerance,diminishedβ-cell mass,and lower blood insulin levels.However,by PW28,glucose tolerance showed some improvement.Both in vivo and in vitro findings collectively indicated that excessive serum corticosterone(CORT)levels of the PCE fetuses may act through the activation of the pancreatic glucocorticoid receptor(GR)and recruitment of histone deacetylase 9(HDAC9),leading to H3K9 deacetylation in promoter and downregulation of insulin-like growth factor 1(IGF1),thereby inhibiting pancreatic islet morphogenesis and insulin synthesis in fetal rats.Furthermore,the PCE offspring after birth exhibited decreased blood CORT levels,increased H3K9 acetylation in promoter and upregulated gene expression of the pancreatic IGF1 promoter region,accompanied by elevated insulin biosynthesis.However,when exposed to chronic stress,the above changes were totally reversed.Conclusively,“glucocorticoid-insulin like growth factor 1(GC-IGF1)axis”programming may be involved in pancreaticβ-cell dysplasia and dysfunction in the PCE female offspring.展开更多
Aim:To determine whether in utero and neonatal exposure to a 60 Hz extremely low frequency electromagnetic field (EMF) results in spermatotoxicity and reproductive dysfunction in the F1 offspring of rats.Methods:Age-m...Aim:To determine whether in utero and neonatal exposure to a 60 Hz extremely low frequency electromagnetic field (EMF) results in spermatotoxicity and reproductive dysfunction in the F1 offspring of rats.Methods:Age-matched, pregnant Sprague-Dawley rats were exposed continuously (21 h/day) to a 60 Hz EMF at field strengths of 0 (sham control),5,83.3 or 500 μT from day 6 of gestation through to day 21 of lactation.The experimentally generated magnetic field was monitored continuously (uninterrupted monitoring over the period of the study) throughout the study.Results:No exposure-related changes were found in exposed or sham-exposed animals with respect to the anogenital distance,preputial separation,testis weight,testicular histology,sperm count,daily sperm production, sperm motility,sperm morphology and reproductive capacity of F1 offspring.Conclusion:Exposure of Sprague- Dawley rats to a 60 Hz EMF at field strengths of up to 500 μT from day 6 of gestation to day 21 of lactation did not produce any detectable alterations in offspring spermatogenesis and fertility.展开更多
OBJECTIVE:To assess the protective role of benazepril,an angiotensin-converting enzyme inhibitor,in renal damage caused by prenatal inflammation.METHODS:Saline or lipopolysaccharide were administered intraperitoneally...OBJECTIVE:To assess the protective role of benazepril,an angiotensin-converting enzyme inhibitor,in renal damage caused by prenatal inflammation.METHODS:Saline or lipopolysaccharide were administered intraperitoneally to pregnant Sprague-Dawley rats on gestation days 8,10,and 12.After birth,offspring received either tap water or benazepril in water between 7 and 68 weeks.Blood pressure,blood urea nitrogen,creatinine,and 24-h urine volume were measured as indices of renal function.Hematoxylin,eosin,periodic acid-Schiff,and Sirius Red staining were used to evaluate renal damage.RESULTS:Postnatal benazepril treatment ameliorated hypertension and restored normal 24-h urine volume and blood urea nitrogen and serum creatinine levels.Benazepril treatment also reduced glycoprotein accumulation and fibrosis in the glomerulus and in tubular epithelial cells and inhibited nuclear factor-kappa B activation.CONCLUSION:Together with our previous findings that postnatal inhibition of nuclear factor-kappa B activation blocks intra-renal renin-angiotensin system activation,our current data demonstrate that intra-renal activation of the renin-angiotensin system interacts with nuclear factor-kappa B activation to cause renal damage in adulthood following prenatal inflammation.展开更多
As we cycle between the states of wakefulness and sleep,a bilateral cholinergic nucleus in the pontine brain stem,the laterodorsal tegmentum(LDT),plays a critical role in controlling salience processing,attention,beha...As we cycle between the states of wakefulness and sleep,a bilateral cholinergic nucleus in the pontine brain stem,the laterodorsal tegmentum(LDT),plays a critical role in controlling salience processing,attention,behavioral arousal,and electrophysiological signatures of the sub-and microstates of sleep.Disorders involving abnormal alterations in behavioral and motivated states,such as drug dependence,likely involve dysfunctions in LDT signaling.In addition,as the LDT exhibits connectivity with the thalamus and mesocortical circuits,as well as receives direct,excitatory input from the prefrontal cortex,a role for the LDT in cognitive symptoms characterizing attention-deficit/hyperactivity disorder(ADHD)including impulsivity,inflexibility,and dysfunctions of attention is suggested.Prenatal nicotine exposure(PNE)is associated with a higher risk for later life development of drug dependence and ADHD,suggesting alteration in development of brain regions involved in these behaviors.PNE has been shown to alter glutamate and cholinergic signaling within the LDT.As glutamate and acetylcholine are major excitatory mediators,these alterations would likely alter excitatory output to target regions in limbic motivational circuits and to thalamic and cortical networks mediating executive control.Further,PNE alters neuronal development and transmission within prefrontal cortex and limbic areas that send input to the LDT,which would compound effects of differential processing within the PNE LDT.When taken together,alterations in signaling in the LDT are likely to play a role in negative behavioral outcomes seen in PNE individuals,including a heightened risk of drug dependence and ADHD behaviors.展开更多
<strong>Objective:</strong> The specific aim of this study was to determine if the currently available cutoff for fentanyl in umbilical cord (UC) was appropriate to distinguish illicit fentanyl exposure fr...<strong>Objective:</strong> The specific aim of this study was to determine if the currently available cutoff for fentanyl in umbilical cord (UC) was appropriate to distinguish illicit fentanyl exposure from therapeutic in-hospital administration of fentanyl. <strong>Study Design</strong><strong>:</strong> Medical record review was conducted for perinatal administration of fentanyl and the detection of fentanyl in the corresponding routine UC toxicology. Specimens were initially tested with immunoassay followed by mass spectrometry (n = 62). <strong>Result:</strong> Excluding a single specimen that was confirmed positive, specimens were below the assays’ limit of quantification. The immunoassay’s mean b/b<sub>0</sub> for the cases that received and did not receive fentanyl prior to delivery was 91.3% ± 10.6% and 98.2% ± 6.5%, respectively (p = 0.003). <strong>Conclusion:</strong> We demonstrated that UC is a suitable specimen type for the detection of fentanyl and that the cutoff selected adequately identifies illicit fentanyl use while not flagging cases where fentanyl was administered by the hospital prior to birth.展开更多
Emerging evidence indicates that prenatal exposure to fine particulate matter(PM2.5)may program metabolic syndrome(MS)in adult offspring.However,the metabolic response to the second hit of a high-fat diet(HFD)(prenata...Emerging evidence indicates that prenatal exposure to fine particulate matter(PM2.5)may program metabolic syndrome(MS)in adult offspring.However,the metabolic response to the second hit of a high-fat diet(HFD)(prenatal PM2.5 exposure as the first hit)in adult offspring and its underlying mechanisms remain poorly understood.Using a whole-body inhalational exposure system,we achieved the following observa-tions.First,prenatal PM2.5 exposure significantly increased the fat mass,inhibited the insulin signaling pathway in chow diet(CD)-fed offspring,and exacerbated HFD-induced metabolic disorders evidenced by impaired insulin signaling in metabolic organs like liver,epididymal white adipose tissue(eWAT),and brown adipose tissue(BAT).Second,prenatal PM2.5 exposure enhanced hepatic lipid accumulation and hypertrophy of adipocytes in eWAT and BAT,accompanied by lipid metabolic disorders in the liver and eWAT.Finally,prenatal exposure to PM2.5 exaggerated HFD-induced cellular senescence in both hepatic and eWAT,as well as cell cycle arrest in BAT,which ultimately led to the activation of chronic inflammation in offspring.In conclusion,prenatal exposure to PM2.5 increased the vulnerability to the second hit of HFD feeding in adult offspring,in which chronic inflammation triggered by cellular senescence may be involved.These findings underscore the heightened vulnerability to metabolic diseases in individuals following early life exposure to air pollution,particularly in the setting of compounding with a high-fat dietary pattern.展开更多
Background: Neurodevelopmental abnormalities in experimental fetal alcohol spectrum disorder (FASD) are associated with impaired signaling through complex pathways that mediate neuronal survival, growth, migration, en...Background: Neurodevelopmental abnormalities in experimental fetal alcohol spectrum disorder (FASD) are associated with impaired signaling through complex pathways that mediate neuronal survival, growth, migration, energy metabolism, and plasticity. Gestational dietary soy prevents alcohol-related impairments in placentation and FASD-associated fetal anomalies. Objective: This study was designed to determine if gestational dietary soy would be sufficient to normalize cognitive function in young adolescent offspring after chronic in utero exposure to alcohol. In addition, efforts were made to characterize the mechanisms of FASD prevention by maternal dietary soy. Methods: Pregnant Long Evans rats were fed isocaloric liquid diets containing 0% or 26% caloric ethanol with casein or soy isolate as the protein source from gestation day 6 through delivery/postnatal day 0 (P0). From P24 - P28, the offspring were subjected to Morris water maze (MWM) testing, and on P35, they were sacrificed to harvest temporal lobes for histopathologic and molecular studies. Results: The in-utero ethanol-exposed offspring exhibited significant performance impairments on the MWM test, and they had a significantly reduced mean brain weight with neuronal loss in the CA1 hippocampal region and evidence of white matter myelin loss. Gestational dietary soy nearly normalized MWM performance and preserved brain weight, hippocampal CA1 architecture, and white matter myelin staining in alcohol-exposed offspring. Mechanistically, the main positive effects of soy included increased temporal lobe expression of HES-1 and HIF-1α, reflecting enhanced Notch signaling, and broadly increased expression of GnRH network molecules, including Erb1, Gper1, GnRH, GnRH-R, KiSS, and KiSS-R, irrespective of gestational ethanol exposure. Conclusions: Dietary soy intervention early in pregnancy may reduce FASD-associated cognitive deficits. The findings suggest that targeting Notch and GnRH-related networks may help reduce long-term disability with FASD. Additional mechanistic and experimental research is needed to determine if longer-duration, postnatal dietary soy could prevent the adverse neurobehavioral effects of FASD.展开更多
Human lung growth involves complex processes.Previous studies have suggested associations of prenatal ambient ozone(O_(3))exposure with impaired lung function,but the causal relationships remain unclear.In this cross-...Human lung growth involves complex processes.Previous studies have suggested associations of prenatal ambient ozone(O_(3))exposure with impaired lung function,but the causal relationships remain unclear.In this cross-sectional cohort study,pulmonary function tests were conducted on recruited participants.Prenatal exposure to the maximum daily 8 h average of daily O_(3)(MDA8 O_(3))and other environmental factors were estimated.Generalized linear model,generalized propensity score,and inverse probability weighting were used to investigate the causal relationship between MDA8 O_(3) and impaired lung function.Finally,a total of 1058 children were included.Each 10μg/m^(3) increase in MDA8 O_(3) during the entire pregnancy,the first trimester,and the third trimester was positively associated with the risk of impaired lung function in childhood,with odd ratios and 95%confidence intervals of 1.52(95%CI:1.06−2.18),1.22(95%CI:1.06−1.41),and 1.47(95%CI:1.19−1.83),respectively.The associations for participants exposed to a high ambient temperature(TM),low relative humidity(RH),and low residential greenness during the pregnancy were higher.Prenatal exposure to higher MDA8 O_(3) concentrations may cause impaired lung function in childhood.The adverse influence of the presence of O_(3) may be amplified by elevated ambient TM and attenuated by RH and residential greenness.展开更多
Maternal cigarette smoking may affect the intrauterine hormonal environment during pregnancy and this early fetal exposure may have detrimental effects on the future trajectory of reproductive health. In this review, ...Maternal cigarette smoking may affect the intrauterine hormonal environment during pregnancy and this early fetal exposure may have detrimental effects on the future trajectory of reproductive health. In this review, we discuss the epidemiological literature on the association between prenatal exposure to maternal cigarette smoking and several aspects of reproductive health. The literature points towards an increased risk of the urogenital malformation cryptorchidism, but a potential protective effect on the risk of hypospadias in sons following prenatal cigarette smoking exposure. Studies on sexual maturation find a tendency towards accelerated pubertal development in exposed boys and girls. In adult life, prenatally exposed men have impaired semen quality compared with unexposed individuals, but an influence on fecundability, that is, the biological ability to reproduce, is less evident. We found no evidence to support an association between prenatal cigarette smoking exposure and testicular cancer. Among adult daughters, research is sparse and inconsistent, but exposure to cigarette smoking in utero may decrease fecundability. In conclusion, prenatal exposure to cigarette smoking may cause some long-term adverse effects on the reproductive health.展开更多
Pyridaben(PY)is a widely used organochlorine acaricide,which can be detected in the peripheral blood of pregnant women.Available evidence suggests that PY has reproductive toxicity.However,it remains uncertain whether...Pyridaben(PY)is a widely used organochlorine acaricide,which can be detected in the peripheral blood of pregnant women.Available evidence suggests that PY has reproductive toxicity.However,it remains uncertain whether prenatal PY exposure impacts neurobehavioral development in offspring.Here,we administered PY to pregnant mice at a dose of 0.5 and 5 mg kg^(-1)day^(-1)via gavage and observed anxietylike behaviors in PY offspring aged five weeks.We then integrated the metabolome and transcriptome of the offspring's brain to explore the underlying mechanism.Metabolome data indicated that the vitamin B6 metabolism pathway was significantly affected,and the pyridoxal 50-phosphate(PLP)concentration and the active form of vitamin B6 was significantly reduced.Moreover,the transcriptome data showed that both PLP generation-related Pdxk and anxiety-related Gad1 were significantly down-regulated.Meanwhile,there was a decreasing trend in the concentration of GABA in the hippocampal DG region.Next,we supplemented PLP at a dose of 20 mg kg^(-1)day^(-1)to the PY offspring via intraperitoneal injection at three weeks.We found up-regulated expression of Pdxk and Gad1 and restored anxiety-like behaviors.This study suggests that prenatal exposure to PY can disrupt vitamin B6 metabolism,reduce the concentration of PLP,down-regulate the expression levels of Pdxk and Gad1,inhibit the production of GABA,and ultimately lead to anxiety-like behaviors in offspring.展开更多
The understanding of the impact of prenatal exposure to metal mixtures on birth weight is limited.We aimed to identify metal mixture components associated with birth weight and to determine additional pairwise interac...The understanding of the impact of prenatal exposure to metal mixtures on birth weight is limited.We aimed to identify metal mixture components associated with birth weight and to determine additional pairwise interactions between metals showing such associations.Concentrations of 18 metals were measured using inductively coupled plasma mass spectrometry in urine samples collected in the 3rd trimester from a prenatal cohort(discovery;n=1849)and the Healthy Baby Cohort(replication;n=7255)in Wuhan,China.In the discovery set,we used two penalized regression models,i.e.,elastic net regression for main effects and a lasso for hierarchical interactions,to identify important mixture components associated with birth weight,which were then replicated.We observed that 8 of the 18 measured metals were retained by elastic net regression,with five metals(vanadium,manganese,iron,cesium,and barium)showing negative associations with Z-scores for birth weight and three metals(cobalt,zinc,and strontium)showing positive associations.In replication set,associations remained significant for vanadium(β=-0.035;95%confidence interval[CI],-0.059 to0.010),cobalt(β=-0.073;95%CI,0.049 to 0.097),and zinc(β=-0.040;95%CI,0.016 to 0.065)after Bonferroni correction.We additionally identified and replicated a single pairwise interaction between iron and copper exposure on birth weight(P<0.001).Using a two-stage analysis,we identified and replicated individual metals and additional pairwise interactions-associated birth weight.The approach could be used in other studies estimating the effect of complex mixtures on human health.展开更多
Objective To investigate the effects of prenatal exposure to lipopolysaccharide(LPS)on blood pressure and body weight of offspring in rats.Methods Sixteen healthy pregnant rats were randomly divided into two groups.Th...Objective To investigate the effects of prenatal exposure to lipopolysaccharide(LPS)on blood pressure and body weight of offspring in rats.Methods Sixteen healthy pregnant rats were randomly divided into two groups.The rats in LPS group were injected intraperitoneally with LPS(0.79 mg·kg-1)at the 8th,10th,12th day of gestation.Those in the control group were only treated with NS.After delivery,all offspring were weighed and blood pressure was measured by tail-cuff method once every two weeks from the 6th to 24th week.In the 15th week,their food intakes were weighed every day.At the end of the 24th week,the rats were put to death by decapitation.Abdominal adipose tissues were taken to weigh,and serum level of leptin was detected by RIA.Results The offspring with prenatal LPS exposure showed increased systemic arterial pressure,heavier body weight,elevated food intake,increased adipose tissue weight and increased circulating leptin compared with controls.Conclusions Prenatal exposure to LPS leads to increases in blood pressure and body weight in rats.展开更多
It has been hypothesized that during the last several decades human sperm count has declined because of prenatal exposure to environmental chemicals. We examined the relation between semen quality and birth year among...It has been hypothesized that during the last several decades human sperm count has declined because of prenatal exposure to environmental chemicals. We examined the relation between semen quality and birth year among 8608 men born from 1922 to 1971 and who from 1968 to 1992 consulted 4 Danish medical centers because of barren marriage. Data were obtained from medical records and by a postal questionnaire to a subset of the population. The sperm concentration was significantly declining with increasing year of birth in 2 of the 4 centers, but this association disappeared when confounders were adjusted for. Within the subset of men born during 1955~1970 comprising 36% of the entire population we revealed a decrease of the average sperm concentration by 1.6 million /ml (95% CI:0.7~2.5) per one advancing year of birth.This finding was consistent across all the 4 centers and robust to adjustment for effects of calendar period, season and duration of sexual abstinence. Effects of age were accounted for by restriction of the sample to men between 20 and 45 years. The findings are compatible with environmental impact in the prenatal period after 1955 but are far from unequivocal evidence that the sperm count in the general male Danish population has changed during the past decades.展开更多
基金supported by awards from National Natural Science Foundation of China [No.81703260]the Education Department of Jiangsu Province [No.16KJB330010]+2 种基金the Science and Technology Department of Jiangsu Province [No.BK20160227]the China Postdoctoral Science Foundation funded project [No.2016M601892]the Priority Academic Program for the Development of Jiangsu Higher Education Institutions(PAPD)
文摘Perfluorooctane sulfonate （PFOS） is a class of stable organic compounds with wide industrial,commercial, and consumer applications, such as in textiles, paper, pesticides, and shampoos;. It is readily absorbed, but poorly eliminated, with the elimination half-life of approximately 5 years;.Hence, there have been concerns regarding its potential damage to human health. Some studies
文摘Objective: Kratom is widely available and literature exploring the effects of prenatal kratom exposure is lacking. This study aims to report a validated method for the detection of mitragynine in the umbilical cord and report our observations for specimens received at a national commercial reference laboratory. Study Design: Assays were validated according to the recommendations of ANSI/ASB. A retrospective evaluation of records at a national reference laboratory was conducted to determine prevalence and co-exposure to other substances of abuse. Result: Mitragynine was detected in 19 of 4456 specimens (0.43%) with concentrations ranging from 4 to >50 ng/g. Thirteen (13) of these specimens were positive for only mitragynine while the other 6 were also positive for either marijuana or opiates. Conclusion: Umbilical cord is a suitable specimen type for the surveillance of maternal kratom use and can be used to identify exposed neonates for further investigations into short- or long- term health consequences.
文摘Background: Prenatal exposure to fentanyl may lead to Neonatal Abstinence Syndrome (NAS), a constellation of symptoms observed when newborns begin withdrawing from addictive substances such as opioids. The use of umbilical cord tissue segments (UC) for newborn toxicology has been increasing due to its apparent long detection window, sensitivity, and ease of collection. However, very little has been reported in the literature concerning the prevalence of in utero exposure to fentanyl and co-exposure with other commonly abused substances. Specific aim: The specific aims of this retrospective study are twofold. We will report prevalence of neonatal exposure to fentanyl for a nationwide high-risk population using UC submitted to a national reference laboratory for routine forensic toxicology analysis and the co-exposure patterns observed for these fentanyl-exposed neonates. Methods: A secondary analysis was performed using historical data for UC received between January 1, 2020 and December 31, 2020 for routine forensic toxicology analysis. Results: During the study period, our laboratory received 23,104 UC for analysis and 9667 (41.8%) of those UC were positive for at least one drug. The prevalence of fentanyl detection was 1.9% (n = 429). Of these 429 specimens there were 407 UC where both fentanyl and norfentanyl were detected. There were 14 UC where only fentanyl was detected and 8 UC where only norfentanyl was detected. When detected, the median concentrations of fentanyl and norfentanyl were 4029 pg/g (IQR: 1696, 9230 pg/g) and 10,756 pg/mg (IQR: 3925, 25,288 pg/g), respectively. Of the 429 positive fentanyl and/or norfentanyl UC, 33 (7.7%) were only positive for fentanyl and/or norfentanyl. Of the 396 polypositive UC, morphine was the highest co-exposure with 243 UC (56.6%) being positive for both fentanyls and morphine. The second most prevalent co-exposure observed was methamphetamine/amphetamine (n = 173;40.3%) followed by cannabinoids (n = 113;26.3%) and benzoylecgonine (cocaine metabolite;n = 106;24.7%). Conclusions: Nonmedical use of fentanyl is an alarming trend in this country including this maternal demographic reported here. Fentanyl was typically found with other commonly abused substances.
基金supported by the National Natural Science Foundation of China(81903331 and 82073660)Open Project of Key Laboratory of Environment and Health,Ministry of Education(2022GWKFJJ05).
文摘Background Prenatal bisphenol exposure has been reported to be associated with lower birth weight and obesity-related indicators in early childhood.These findings warrant an investigation of the relationship between prenatal bisphenol exposure and the dynamic growth of offspring.This study aimed to evaluate the relationship of maternal bisphenol concentration in urine with the body mass index(BMI)growth trajectory of children aged up to two years and to identify the critical exposure periods.Methods A total of 826 mother–offspring pairs were recruited from Wuhan Children’s Hospital between November 2013 and March 2015.Maternal urine samples collected during the first,second,and third trimesters were analyzed for bisphenol A(BPA),bisphenol S,and bisphenol F(BPF)concentrations.Measurements of length and weight were taken at 0,1,3,6,8,12,18,and 24 months.Children's BMI was standardized using the World Health Organization reference,and group-based trajectory modeling was used to identify BMI growth trajectories.The associations between prenatal bisphenol exposure and BMI growth trajectory patterns were assessed using multinomial logistic regression models.Results The BMI growth trajectories of the 826 children were categorized into four patterns:low-stable(n=134,16.2%),low-increasing(n=142,17.2%),moderate-stable(n=350,42.4%),and moderate-increasing(n=200,24.2%).After adjusting for potential confounders,we observed that prenatal exposure to BPA during the second trimester[odds ratio(OR)=2.20,95%confidence interval(CI)=1.09–4.43]and BPF during the third trimester(OR=3.28,95%CI=1.55–6.95)at the highest quartile concentration were associated with an increased likelihood of the low-increasing BMI trajectory.Furthermore,in the subgroup analysis by infant sex,the positive association between the highest quartile of prenatal average urinary BPF concentration during the whole pregnancy and the low-increasing BMI trajectory was found only in girls(OR=2.82,95%CI=1.04–7.68).Conclusion Our study findings suggest that prenatal exposure to BPA and BPF(a commonly used substitute for BPA)is associated with BMI growth trajectories in offspring during the first two years,increasing the likelihood of the low-increasing pattern.
基金supported by the National Key Research and Development Program of China (No.2020YFA0803900)。
文摘Amoxicillin,a widely used antibiotic in human and veterinary pharmaceuticals,is now considered as an“emerging contaminant”because it exists widespreadly in the environment and brings a series of adverse outcomes.Currently,systematic studies about the developmental toxicity of amoxicillin are still lacking.We explored the potential effects of amoxicillin exposure on pregnancy outcomes,maternal/fetal serum phenotypes,and fetal multiple organ development in mice,at different doses(75,150,300 mg/(kg·day))during late-pregnancy,or at a dose of 300 mg/(kg·day)during different stages(mid-/latepregnancy)and courses(single-/multi-course).Results showed that prenatal amoxicillin exposure(PAmE)had no significant infuence on the body weights of dams,but it could inhibit the physical development and reduce the survival rate of fetuses,especially during the midpregnancy.Meanwhile,PAmE altered multiple maternal/fetal serum phenotypes,especially in fetuses.Fetal multi-organ function results showed that PAmE inhibited testicular/adrenal steroid synthesis,long bone/cartilage and hippocampal development,and enhanced ovarian steroid synthesis and hepatic glycogenesis/lipogenesis,and the order of severity might be gonad(testis,ovary)>liver>others.Further analysis found that PAmE-induced multiorgan developmental and functional alterations had differences in stages,courses and fetal gender,and the most obvious changes might be in high-dose,late-pregnancy and multicourse,but there was no typical rule of a dose-response relationship.In conclusion,this study confirmed that PAmE could cause abnormal development and multi-organ function alterations,which deepens our understanding of the risk of PAmE and provides an experimental basis for further exploration of the long-term harm.
基金the Natural Science Foundation of Henan Province in China,No.102102310156the Foundation of Xinxiang Technology Bureau in China,No.ZG14004
文摘Prenatal alcohol exposure disrupts the development of normal fetal respiratory function, but whether it perturbs respiratory rhythmical discharge activity is unclear. Furthermore, it is unknown whether the 5-hydroxytryptamine 2A receptor（5-HT2AR） is involved in the effects of prenatal alcohol exposure. In the present study, pregnant female rats received drinking water containing alcohol at concentrations of 0%, 1%, 2%, 4%, 8% or 10%（v/v） throughout the gestation period. Slices of the medulla from 2-day-old neonatal rats were obtained to record respiratory rhythmical discharge activity. 5-HT2 AR protein and m RNA levels in the pre-B？tzinger complex of the respiratory center were measured by western blot analysis and quantitative RT-PCR, respectively. Compared with the 0% alcohol group, respiratory rhythmical discharge activity in medullary slices in the 4%, 8% and 10% alcohol groups was decreased, and the reduction was greatest in the 8% alcohol group. Respiratory rhythmical discharge activity in the 10% alcohol group was irregular. Thus, 8% was the most effective alcohol concentration at attenuating respiratory rhythmical discharge activity. These findings suggest that prenatal alcohol exposure attenuates respiratory rhythmical discharge activity in neonatal rats by downregulating 5-HT2 AR protein and m RNA levels.
基金supported by the National Key Research and Development Program of China(No.2020YFA0803900)the National Natural Science Foundation of China(No.81872943)。
文摘Prednisone is a synthetic glucocorticoid that is commonly used in both human and veterinary medication.Now,it is also recognized as an emerging environmental contaminant.Pregnantwomenmay be exposed to prednisone actively or passively throughmultiple pathways and cause developmental toxicity to the fetus.However,the impact of prenatal prednisone exposure(PPE)on fetal kidney development remains unclear.In this study,pregnant mice were administered prednisone intragastrically during full-term pregnancy with different doses(0.25,0.5,or 1 mg/(kg·day)),or at the dose of 1 mg/(kg·day)in different gestational days(GD)(GD0-9,GD10-18,or GD0-18).The pregnant mice were euthanized on GD18.HE staining revealed fetal kidney dysplasia,with an enlarged glomerular Bowman’s capsule space and a reduced capillary network in the PPE groups.The expression of the podocyte and the mesangial cell marker genes was significantly reduced in the PPE groups.However,overall gene expression in renal tubules and collecting ducts were markedly increased.All of the above effects were more pronounced in high-dose,full-term pregnancy,and female fetuses.Studies on the mechanism of the female fetal kidney have revealed that PPE reduced the expression of Six2,increased the expression of Hnf1β,Hnf4α,and Wnt9b,and inhibited the expression of glial cell line-derived neurotrophic factor(GDNF)and Notch signaling pathways.In conclusion,this study demonstrated that there is a sex difference in the developmental toxicity of PPE to the fetal kidney,and the time effect is manifested as full-term pregnancy>early pregnancy>mid-late pregnancy.
基金supported by grants from the National Key Research and Development Program of China(2020YFA0803900)the National Natural Science Foundation of China(U23A20407,82414020,81703631)the Hubei Provincial Natural Science Foundation of China(2024AFB742)。
文摘Prenatal caffeine exposure(PCE)leads to intrauterine growth retardation and altered glucose homeostasis after birth,but the underlying mechanism remains unclear.This study aims to investigate the alteration of pancreatic development and insulin biosynthesis in the PCE female offspring and explore the intrauterine programming mechanism.Pregnant rats were orally treated with 120 mg/(kg·day)of caffeine from gestational day(GD)9 to 20.Results showed that fetal pancreaticβ-cells in the PCE group exhibited reduced mass and impaired insulin synthesis function,as evidenced by decreased expression of developmental and functional genes and reduced pancreatic insulin content.At postnatal week(PW)12,the PCE offspring exhibited glucose intolerance,diminishedβ-cell mass,and lower blood insulin levels.However,by PW28,glucose tolerance showed some improvement.Both in vivo and in vitro findings collectively indicated that excessive serum corticosterone(CORT)levels of the PCE fetuses may act through the activation of the pancreatic glucocorticoid receptor(GR)and recruitment of histone deacetylase 9(HDAC9),leading to H3K9 deacetylation in promoter and downregulation of insulin-like growth factor 1(IGF1),thereby inhibiting pancreatic islet morphogenesis and insulin synthesis in fetal rats.Furthermore,the PCE offspring after birth exhibited decreased blood CORT levels,increased H3K9 acetylation in promoter and upregulated gene expression of the pancreatic IGF1 promoter region,accompanied by elevated insulin biosynthesis.However,when exposed to chronic stress,the above changes were totally reversed.Conclusively,“glucocorticoid-insulin like growth factor 1(GC-IGF1)axis”programming may be involved in pancreaticβ-cell dysplasia and dysfunction in the PCE female offspring.
文摘Aim:To determine whether in utero and neonatal exposure to a 60 Hz extremely low frequency electromagnetic field (EMF) results in spermatotoxicity and reproductive dysfunction in the F1 offspring of rats.Methods:Age-matched, pregnant Sprague-Dawley rats were exposed continuously (21 h/day) to a 60 Hz EMF at field strengths of 0 (sham control),5,83.3 or 500 μT from day 6 of gestation through to day 21 of lactation.The experimentally generated magnetic field was monitored continuously (uninterrupted monitoring over the period of the study) throughout the study.Results:No exposure-related changes were found in exposed or sham-exposed animals with respect to the anogenital distance,preputial separation,testis weight,testicular histology,sperm count,daily sperm production, sperm motility,sperm morphology and reproductive capacity of F1 offspring.Conclusion:Exposure of Sprague- Dawley rats to a 60 Hz EMF at field strengths of up to 500 μT from day 6 of gestation to day 21 of lactation did not produce any detectable alterations in offspring spermatogenesis and fertility.
基金Natural Science Foundation-funded Project:Role of HMGB-1-TLR4/RAGE Pathway Over-Expression in Increased Offspring's Pyelonephritis Sensitivity Induced by Pregnant Inflammatory Stimulation(No.81703522)the Role and Mechanisms of Decidual NK Cell Abnormality in Prenatal Inflammation-Induced Offspring's Immune System Dysfunction and Hypertension(No.81520108029)+1 种基金Role of AMPK/NK-ΚB Signal Pathway Imbalance in Offspring's Hypertension Induced by Pregnant Inflammatory Stimulation(No.81703521)Roles and Mechanisms of Mitochondrial Dyshomeostasis in the Hypersensitivity of Cardiac Damage Responding to Cardiac Risk Factors in Offspring of Prenatal Inflammatory Stimulation(No.81773742)。
文摘OBJECTIVE:To assess the protective role of benazepril,an angiotensin-converting enzyme inhibitor,in renal damage caused by prenatal inflammation.METHODS:Saline or lipopolysaccharide were administered intraperitoneally to pregnant Sprague-Dawley rats on gestation days 8,10,and 12.After birth,offspring received either tap water or benazepril in water between 7 and 68 weeks.Blood pressure,blood urea nitrogen,creatinine,and 24-h urine volume were measured as indices of renal function.Hematoxylin,eosin,periodic acid-Schiff,and Sirius Red staining were used to evaluate renal damage.RESULTS:Postnatal benazepril treatment ameliorated hypertension and restored normal 24-h urine volume and blood urea nitrogen and serum creatinine levels.Benazepril treatment also reduced glycoprotein accumulation and fibrosis in the glomerulus and in tubular epithelial cells and inhibited nuclear factor-kappa B activation.CONCLUSION:Together with our previous findings that postnatal inhibition of nuclear factor-kappa B activation blocks intra-renal renin-angiotensin system activation,our current data demonstrate that intra-renal activation of the renin-angiotensin system interacts with nuclear factor-kappa B activation to cause renal damage in adulthood following prenatal inflammation.
文摘As we cycle between the states of wakefulness and sleep,a bilateral cholinergic nucleus in the pontine brain stem,the laterodorsal tegmentum(LDT),plays a critical role in controlling salience processing,attention,behavioral arousal,and electrophysiological signatures of the sub-and microstates of sleep.Disorders involving abnormal alterations in behavioral and motivated states,such as drug dependence,likely involve dysfunctions in LDT signaling.In addition,as the LDT exhibits connectivity with the thalamus and mesocortical circuits,as well as receives direct,excitatory input from the prefrontal cortex,a role for the LDT in cognitive symptoms characterizing attention-deficit/hyperactivity disorder(ADHD)including impulsivity,inflexibility,and dysfunctions of attention is suggested.Prenatal nicotine exposure(PNE)is associated with a higher risk for later life development of drug dependence and ADHD,suggesting alteration in development of brain regions involved in these behaviors.PNE has been shown to alter glutamate and cholinergic signaling within the LDT.As glutamate and acetylcholine are major excitatory mediators,these alterations would likely alter excitatory output to target regions in limbic motivational circuits and to thalamic and cortical networks mediating executive control.Further,PNE alters neuronal development and transmission within prefrontal cortex and limbic areas that send input to the LDT,which would compound effects of differential processing within the PNE LDT.When taken together,alterations in signaling in the LDT are likely to play a role in negative behavioral outcomes seen in PNE individuals,including a heightened risk of drug dependence and ADHD behaviors.
文摘<strong>Objective:</strong> The specific aim of this study was to determine if the currently available cutoff for fentanyl in umbilical cord (UC) was appropriate to distinguish illicit fentanyl exposure from therapeutic in-hospital administration of fentanyl. <strong>Study Design</strong><strong>:</strong> Medical record review was conducted for perinatal administration of fentanyl and the detection of fentanyl in the corresponding routine UC toxicology. Specimens were initially tested with immunoassay followed by mass spectrometry (n = 62). <strong>Result:</strong> Excluding a single specimen that was confirmed positive, specimens were below the assays’ limit of quantification. The immunoassay’s mean b/b<sub>0</sub> for the cases that received and did not receive fentanyl prior to delivery was 91.3% ± 10.6% and 98.2% ± 6.5%, respectively (p = 0.003). <strong>Conclusion:</strong> We demonstrated that UC is a suitable specimen type for the detection of fentanyl and that the cutoff selected adequately identifies illicit fentanyl use while not flagging cases where fentanyl was administered by the hospital prior to birth.
基金supported by National Natural Science Foundation of China(grant numbers 82273590,82173480).
文摘Emerging evidence indicates that prenatal exposure to fine particulate matter(PM2.5)may program metabolic syndrome(MS)in adult offspring.However,the metabolic response to the second hit of a high-fat diet(HFD)(prenatal PM2.5 exposure as the first hit)in adult offspring and its underlying mechanisms remain poorly understood.Using a whole-body inhalational exposure system,we achieved the following observa-tions.First,prenatal PM2.5 exposure significantly increased the fat mass,inhibited the insulin signaling pathway in chow diet(CD)-fed offspring,and exacerbated HFD-induced metabolic disorders evidenced by impaired insulin signaling in metabolic organs like liver,epididymal white adipose tissue(eWAT),and brown adipose tissue(BAT).Second,prenatal PM2.5 exposure enhanced hepatic lipid accumulation and hypertrophy of adipocytes in eWAT and BAT,accompanied by lipid metabolic disorders in the liver and eWAT.Finally,prenatal exposure to PM2.5 exaggerated HFD-induced cellular senescence in both hepatic and eWAT,as well as cell cycle arrest in BAT,which ultimately led to the activation of chronic inflammation in offspring.In conclusion,prenatal exposure to PM2.5 increased the vulnerability to the second hit of HFD feeding in adult offspring,in which chronic inflammation triggered by cellular senescence may be involved.These findings underscore the heightened vulnerability to metabolic diseases in individuals following early life exposure to air pollution,particularly in the setting of compounding with a high-fat dietary pattern.
文摘Background: Neurodevelopmental abnormalities in experimental fetal alcohol spectrum disorder (FASD) are associated with impaired signaling through complex pathways that mediate neuronal survival, growth, migration, energy metabolism, and plasticity. Gestational dietary soy prevents alcohol-related impairments in placentation and FASD-associated fetal anomalies. Objective: This study was designed to determine if gestational dietary soy would be sufficient to normalize cognitive function in young adolescent offspring after chronic in utero exposure to alcohol. In addition, efforts were made to characterize the mechanisms of FASD prevention by maternal dietary soy. Methods: Pregnant Long Evans rats were fed isocaloric liquid diets containing 0% or 26% caloric ethanol with casein or soy isolate as the protein source from gestation day 6 through delivery/postnatal day 0 (P0). From P24 - P28, the offspring were subjected to Morris water maze (MWM) testing, and on P35, they were sacrificed to harvest temporal lobes for histopathologic and molecular studies. Results: The in-utero ethanol-exposed offspring exhibited significant performance impairments on the MWM test, and they had a significantly reduced mean brain weight with neuronal loss in the CA1 hippocampal region and evidence of white matter myelin loss. Gestational dietary soy nearly normalized MWM performance and preserved brain weight, hippocampal CA1 architecture, and white matter myelin staining in alcohol-exposed offspring. Mechanistically, the main positive effects of soy included increased temporal lobe expression of HES-1 and HIF-1α, reflecting enhanced Notch signaling, and broadly increased expression of GnRH network molecules, including Erb1, Gper1, GnRH, GnRH-R, KiSS, and KiSS-R, irrespective of gestational ethanol exposure. Conclusions: Dietary soy intervention early in pregnancy may reduce FASD-associated cognitive deficits. The findings suggest that targeting Notch and GnRH-related networks may help reduce long-term disability with FASD. Additional mechanistic and experimental research is needed to determine if longer-duration, postnatal dietary soy could prevent the adverse neurobehavioral effects of FASD.
基金supported by the National Natural Science Foundation of China(42175181 and 42375180)the Natural Science Foundation of Guangdong Province(2024A1515012088)the Guangdong Natural Science Foundation General Program(2025A1515011676).
文摘Human lung growth involves complex processes.Previous studies have suggested associations of prenatal ambient ozone(O_(3))exposure with impaired lung function,but the causal relationships remain unclear.In this cross-sectional cohort study,pulmonary function tests were conducted on recruited participants.Prenatal exposure to the maximum daily 8 h average of daily O_(3)(MDA8 O_(3))and other environmental factors were estimated.Generalized linear model,generalized propensity score,and inverse probability weighting were used to investigate the causal relationship between MDA8 O_(3) and impaired lung function.Finally,a total of 1058 children were included.Each 10μg/m^(3) increase in MDA8 O_(3) during the entire pregnancy,the first trimester,and the third trimester was positively associated with the risk of impaired lung function in childhood,with odd ratios and 95%confidence intervals of 1.52(95%CI:1.06−2.18),1.22(95%CI:1.06−1.41),and 1.47(95%CI:1.19−1.83),respectively.The associations for participants exposed to a high ambient temperature(TM),low relative humidity(RH),and low residential greenness during the pregnancy were higher.Prenatal exposure to higher MDA8 O_(3) concentrations may cause impaired lung function in childhood.The adverse influence of the presence of O_(3) may be amplified by elevated ambient TM and attenuated by RH and residential greenness.
文摘Maternal cigarette smoking may affect the intrauterine hormonal environment during pregnancy and this early fetal exposure may have detrimental effects on the future trajectory of reproductive health. In this review, we discuss the epidemiological literature on the association between prenatal exposure to maternal cigarette smoking and several aspects of reproductive health. The literature points towards an increased risk of the urogenital malformation cryptorchidism, but a potential protective effect on the risk of hypospadias in sons following prenatal cigarette smoking exposure. Studies on sexual maturation find a tendency towards accelerated pubertal development in exposed boys and girls. In adult life, prenatally exposed men have impaired semen quality compared with unexposed individuals, but an influence on fecundability, that is, the biological ability to reproduce, is less evident. We found no evidence to support an association between prenatal cigarette smoking exposure and testicular cancer. Among adult daughters, research is sparse and inconsistent, but exposure to cigarette smoking in utero may decrease fecundability. In conclusion, prenatal exposure to cigarette smoking may cause some long-term adverse effects on the reproductive health.
基金supported by the National Key R&D Program of China(grant number 2021YFC2701100 and 2021YFC2701102)China-U.S.Program for Biomedical Collaborative Research(NSFCNIH)(grant number 81961128022)+1 种基金the National Natural Science Foundation of China(grant number 81903351)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘Pyridaben(PY)is a widely used organochlorine acaricide,which can be detected in the peripheral blood of pregnant women.Available evidence suggests that PY has reproductive toxicity.However,it remains uncertain whether prenatal PY exposure impacts neurobehavioral development in offspring.Here,we administered PY to pregnant mice at a dose of 0.5 and 5 mg kg^(-1)day^(-1)via gavage and observed anxietylike behaviors in PY offspring aged five weeks.We then integrated the metabolome and transcriptome of the offspring's brain to explore the underlying mechanism.Metabolome data indicated that the vitamin B6 metabolism pathway was significantly affected,and the pyridoxal 50-phosphate(PLP)concentration and the active form of vitamin B6 was significantly reduced.Moreover,the transcriptome data showed that both PLP generation-related Pdxk and anxiety-related Gad1 were significantly down-regulated.Meanwhile,there was a decreasing trend in the concentration of GABA in the hippocampal DG region.Next,we supplemented PLP at a dose of 20 mg kg^(-1)day^(-1)to the PY offspring via intraperitoneal injection at three weeks.We found up-regulated expression of Pdxk and Gad1 and restored anxiety-like behaviors.This study suggests that prenatal exposure to PY can disrupt vitamin B6 metabolism,reduce the concentration of PLP,down-regulate the expression levels of Pdxk and Gad1,inhibit the production of GABA,and ultimately lead to anxiety-like behaviors in offspring.
基金supported by the National Natural Science Foundation of China(42077398),Program for HUST Academic Frontier Youth Team(2018QYTD12)and the National Institute of Environmental Health Sciences(R01 ES024381 and R01 ES025214).
文摘The understanding of the impact of prenatal exposure to metal mixtures on birth weight is limited.We aimed to identify metal mixture components associated with birth weight and to determine additional pairwise interactions between metals showing such associations.Concentrations of 18 metals were measured using inductively coupled plasma mass spectrometry in urine samples collected in the 3rd trimester from a prenatal cohort(discovery;n=1849)and the Healthy Baby Cohort(replication;n=7255)in Wuhan,China.In the discovery set,we used two penalized regression models,i.e.,elastic net regression for main effects and a lasso for hierarchical interactions,to identify important mixture components associated with birth weight,which were then replicated.We observed that 8 of the 18 measured metals were retained by elastic net regression,with five metals(vanadium,manganese,iron,cesium,and barium)showing negative associations with Z-scores for birth weight and three metals(cobalt,zinc,and strontium)showing positive associations.In replication set,associations remained significant for vanadium(β=-0.035;95%confidence interval[CI],-0.059 to0.010),cobalt(β=-0.073;95%CI,0.049 to 0.097),and zinc(β=-0.040;95%CI,0.016 to 0.065)after Bonferroni correction.We additionally identified and replicated a single pairwise interaction between iron and copper exposure on birth weight(P<0.001).Using a two-stage analysis,we identified and replicated individual metals and additional pairwise interactions-associated birth weight.The approach could be used in other studies estimating the effect of complex mixtures on human health.
文摘Objective To investigate the effects of prenatal exposure to lipopolysaccharide(LPS)on blood pressure and body weight of offspring in rats.Methods Sixteen healthy pregnant rats were randomly divided into two groups.The rats in LPS group were injected intraperitoneally with LPS(0.79 mg·kg-1)at the 8th,10th,12th day of gestation.Those in the control group were only treated with NS.After delivery,all offspring were weighed and blood pressure was measured by tail-cuff method once every two weeks from the 6th to 24th week.In the 15th week,their food intakes were weighed every day.At the end of the 24th week,the rats were put to death by decapitation.Abdominal adipose tissues were taken to weigh,and serum level of leptin was detected by RIA.Results The offspring with prenatal LPS exposure showed increased systemic arterial pressure,heavier body weight,elevated food intake,increased adipose tissue weight and increased circulating leptin compared with controls.Conclusions Prenatal exposure to LPS leads to increases in blood pressure and body weight in rats.
文摘It has been hypothesized that during the last several decades human sperm count has declined because of prenatal exposure to environmental chemicals. We examined the relation between semen quality and birth year among 8608 men born from 1922 to 1971 and who from 1968 to 1992 consulted 4 Danish medical centers because of barren marriage. Data were obtained from medical records and by a postal questionnaire to a subset of the population. The sperm concentration was significantly declining with increasing year of birth in 2 of the 4 centers, but this association disappeared when confounders were adjusted for. Within the subset of men born during 1955~1970 comprising 36% of the entire population we revealed a decrease of the average sperm concentration by 1.6 million /ml (95% CI:0.7~2.5) per one advancing year of birth.This finding was consistent across all the 4 centers and robust to adjustment for effects of calendar period, season and duration of sexual abstinence. Effects of age were accounted for by restriction of the sample to men between 20 and 45 years. The findings are compatible with environmental impact in the prenatal period after 1955 but are far from unequivocal evidence that the sperm count in the general male Danish population has changed during the past decades.
