The Endocrine Disruption of Prenatal Phthalate Exposure in Mother and Offspring.
Ontology highlight
ABSTRACT:
SUBMITTER: Qian Y
PROVIDER: S-EPMC7483495 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
The Endocrine Disruption of Prenatal Phthalate Exposure in Mother and Offspring.
Qian Yiyu Y Shao Hailing H Ying Xinxin X Huang Wenle W Hua Ying Y
Frontiers in public health 20200828
Phthalates are a group of ubiquitous synthetic endocrine-disrupting chemicals. Fetal and neonatal periods are particularly susceptible to endocrine disorders, which prenatal exposure to phthalates causes. There is increasing evidence concerning the potential endocrine disrupting for phthalate exposure during pregnancy. This article aims to review the endocrine impairment and potential outcomes of prenatal phthalate exposure. Prenatal exposure phthalates would disrupt the levels of thyroid, sex h ...[more]
Similar Datasets
Project description:Phthalates are extensively used as plasticizers in a variety of daily-life products, resulting in widespread distribution in aquatic environments. However, limited information is available on the endocrine disrupting effects of phthalates in aquatic organisms. The aim of the present study was to examine whether exposure to mono-(2-ethylhexyl) phthalate (MEHP), the hydrolytic metabolite of di-(2-ethylhexyl) phthalate (DEHP) disrupts thyroid endocrine system in fish. In this study, zebrafish (Danio rerio) embryos were exposed to different concentrations of MEHP (1.6, 8, 40, and 200 μg/L) from 2 h post-fertilization (hpf) to 168 hpf. The whole-body content of thyroid hormone and transcription of genes involved in the hypothalamic-pituitary-thyroid (HPT) axis were examined. Treatment with MEHP significantly decreased whole-body T4 contents and increased whole-body T3 contents, indicating thyroid endocrine disruption. The upregulation of genes related to thyroid hormone metabolism (Dio2 and UGT1ab) might be responsible for decreased T4 contents. Elevated gene transcription of Dio1 was also observed in this study, which might assist to degrade increased T3 contents. Exposure to MEHP also significantly induced transcription of genes involved in thyroid development (Nkx2.1 and Pax8) and thyroid hormone synthesis (TSHβ, NIS and TG). However, the genes encoding proteins involved in TH transport (transthyretin, TTR) was transcriptionally significantly down-regulated after exposure to MEHP. Overall, these results demonstrate that acute exposure to MEHP alters whole-body contents of thyroid hormones in zebrafish embryos/larvae and changes the transcription of genes involved in the HPT axis, thus exerting thyroid endocrine toxicity.
| S-EPMC3962405 | biostudies-literature
Project description:Phthalates are endocrine-disrupting chemicals that can cross the placenta and affect the fetal epigenome. Among various epigenetic regulators of gene expression, long noncoding RNAs (lncRNAs) are important players that may also be involved in the manifestation of endocrine-disrupting chemical toxicity. We sought to explore the association between maternal urinary phthalate metabolite concentrations and lncRNA expression in human placenta to better understand potential mechanisms through which lncRNAs participate in mediating phthalate toxicity. Ten patients with uncomplicated dichorionic diamniotic twin pregnancies at term were included in this study. Urinary (n = 10) and placenta samples (n = 20) were collected for all participants. Urinary samples were analyzed for 15 phthalate metabolites and 2 phthalate alternative metabolites. Real-time PCR arrays were used to identify and quantify 87 lncRNAs from the placental samples. We tested the Spearman correlation matrix to compare prenatal phthalate measures against placental lncRNA levels. lncRNA levels showed large variations across samples, with no significant differences in lncRNA expression within twin pairs. Mono-(carboxynonyl) phthalate demonstrated consistently strong correlations with most lncRNAs. The strongest correlation was observed between mono-hydroxyisobutyl phthalate and LOC91450 (Rspearman = 0.88, p < .001). This correlation remained significant after Bonferroni adjustment. Other strong correlations were observed between mono-isobutyl phthalate, DPP10 and HOTTIP (Rspearman = -0.91, p < .001). AIRN, DACT3.AS1, DLX6, DPP10, HOTTIP, LOC143666, and LOC91450 were strongly correlated with the greatest number of phthalate metabolites. Further studies are needed to validate these results and understand if the altered expression of lncRNAs in human placenta has clinical significance.
| S-EPMC5917778 | biostudies-other
Project description:In utero exposure to endocrine-disrupting chemicals may contribute to testicular dysgenesis syndrome (TDS), a proposed constellation of increasingly common male reproductive tract abnormalities (including hypospadias, cryptorchidism, hypospermatogenesis, and testicular cancer). Male rats exposed in utero to certain phthalate plasticizers exhibit multinucleated germ cell (MNG) induction and suppressed steroidogenic gene expression and testosterone production in the fetal testis, causing TDS-consistent effects of hypospadias and cryptorchidism. Mice exposed to phthalates in utero exhibit MNG induction only. This disparity in response demonstrates a species-specific sensitivity to phthalate-induced suppression of fetal Leydig cell steroidogenesis. Importantly, ex vivo phthalate exposure of the fetal testis does not recapitulate the species-specific endocrine disruption, demonstrating the need for a new bioassay to assess the human response to phthalates.In this study, we aimed to develop and validate a rat and mouse testis xenograft bioassay of phthalate exposure and examine the human fetal testis response.Fetal rat, mouse, and human testes were xenografted into immunodeficient rodent hosts, and hosts were gavaged with a range of phthalate doses over multiple days. Xenografts were harvested and assessed for histopathology and steroidogenic end points.Consistent with the in utero response, phthalate exposure induced MNG formation in rat and mouse xenografts, but only rats exhibited suppressed steroidogenesis. Across a range of doses, human fetal testis xenografts exhibited MNG induction but were resistant to suppression of steroidogenic gene expression.Phthalate exposure of grafted human fetal testis altered fetal germ cells but did not reduce expression of genes that regulate fetal testosterone biosynthesis.
| S-EPMC3440087 | biostudies-literature
Project description:Exposure to phthalates has been shown to impede the human endocrine system, resulting in deleterious effects on pregnant women and their children. Phthalates modify DNA methylation patterns in infant cord blood. We examined the association between prenatal phthalate exposure and DNA methylation patterns in cord blood in a Korean birth cohort. Phthalate levels were measured in 274 maternal urine samples obtained during late pregnancy and 102 neonatal urine samples obtained at birth, and DNA methylation levels were measured in cord blood samples. For each infant in the cohort, associations between CpG methylation and both maternal and neonate phthalate levels were analyzed using linear mixed models. The results were combined with those from a meta-analysis of the levels of phthalates in maternal and neonatal urine samples, which were also analyzed for MEOHP, MEHHP, MnBP, and DEHP. This meta-analysis revealed significant associations between the methylation levels of CpG sites near the CHN2 and CUL3 genes, which were also associated with MEOHP and MnBP in neonatal urine. When the data were stratified by the sex of the infant, MnBP concentration was found to be associated with one CpG site near the OR2A2 and MEGF11 genes in female infants. In contrast, the concentrations of the three maternal phthalates showed no significant association with CpG site methylation. Furthermore, the data identified distinct differentially methylated regions in maternal and neonatal urine samples following exposure to phthalates. The CpGs with methylation levels that were positively associated with phthalate levels (particularly MEOHP and MnBP) were found to be enriched genes and related pathways. These results indicate that prenatal phthalate exposure is significantly associated with DNA methylation at multiple CpG sites. These alterations in DNA methylation may serve as biomarkers of maternal exposure to phthalates in infants and are potential candidates for investigating the mechanisms by which phthalates impact maternal and neonatal health.
| S-EPMC10148847 | biostudies-literature
Project description:BackgroundDi-(2-ethylhexyl) phthalate (DEHP) is a plasticizer used to increase the flexibility of polyvinyl chloride. DEHP and its active metabolite mono-(2-ethylhexyl) phthalate are detected in many biological fluids during fetal and postnatal life. In rodent models, in utero DEHP exposure has been shown to alter sexual organ development, decrease testosterone and aldosterone production, increase body and epididymal adipose tissue weight, and raise serum lipids and glucose levels in male offspring.ObjectivesThe objective of this study is to characterize the effects of in utero DEHP exposure on adipose tissue development and function in male offspring.MethodsSprague-Dawley pregnant dams were gavaged 1, 20, 50 or 300?mg DEHP per kg per day from gestational day 14 until birth.ResultsGlobal gene expression analyses of postnatal day 60 male offspring that were exposed in utero to 300?mg DEHP per kg per day revealed increased expression of immune response and inflammation markers, and increased expression of differentiation pathway genes in the epididymal whole-adipose tissue and isolated stromal vascular fraction. C-reactive protein and tumor necrosis factor (TNF) serum levels were increased in the 300?mg DEHP in utero-exposed offspring. TNF levels in adipose tissue homogenates were increased in the 50 and 300?mg DEHP in utero-exposed offspring. Immunofluorescence studies revealed focal macrophage infiltration in whole-adipose tissue confirmed by increased CD163 tissue content.ConclusionsIn utero DEHP exposure promotes local adipose tissue inflammation and chronic low-grade systemic inflammation. Moreover, evidence is presented, suggesting that DEHP increases the differentiation capacity of the pre-adipocytes of male offspring without affecting total body weight.
| S-EPMC4042311 | biostudies-literature
Project description:Although prenatal tobacco exposure (PTE) is associated with several adverse offspring mental health outcomes, mechanisms remain unclear. We test whether associations between PTE and offspring psychopathology are explained by birthweight, one of the earliest-occurring outcomes of PTE. The analysis focuses on 238 offspring from a family study of depression with (1) collected prenatal histories and (2) at least one clinical interview in adulthood to assess psychiatric problems. Exposure was categorized by maternal smoking of ≥10 cigarettes daily/nearly daily; diagnostic outcomes were confirmed by clinicians using the best-estimate procedure, blind to exposure. After adjusting for potential confounders, PTE was associated with 0.7lb(9%) lower birthweight (p=0.0002), increased rates of disruptive behavior disorders [males: OR=2.66(1.15,6.16), and (trend) substance use disorders [females: OR=2.23(0.98,5.09)], and decreased rates of mood disorders (males: OR=0.42(0.17,0.98)]. Birthweight was not independently associated with diagnoses and did not mediate the association between exposure and psychopathology. Maternal smoking has long-term adverse consequences for offspring. Although birthweight cannot be manipulated, smoking is a modifiable risk factor. Thus, cessation efforts focused on pregnant women may not only improve maternal wellbeing, but also mitigate adverse proximal (e.g., birthweight) and long-term (psychopathology) outcomes in offspring.
| S-EPMC5438886 | biostudies-literature
Project description:Phthalates are a class of high volume production chemicals used as plasticizers for household and industrial use. Several members of this chemical family have endocrine disrupting activity. Owing to ubiquitous environmental distribution and exposure of human population at all stages of life, phthalate contamination is a continuous global public health problem. Clinical and experimental studies have indicated that several phthalates are associated with adverse effects on development and function of human and animal systems especially the reproductive system and exposures during pregnancy and early childhood are by far of utmost concern. Sex hormone-binding globulin (SHBG) is a plasma carrier protein that binds androgens and estrogens and represents a potential target for phthalate endocrine disruptor function in the body. In the present study, the binding mechanism of the nine phthalates i.e. DMP, DBP, DIBP, BBP, DNHP, DEHP, DNOP, DINP, DIDP with human SHBG was delineated by molecular docking simulation. Docking complexes of the nine phthalates displayed interactions with 15-31 amino acid residues of SHBG and a commonality of 55-95% interacting residues between natural ligand of SHBG, dihydrotestosterone, and the nine phthalate compounds was observed. The binding affinity values were more negative for long chain phthalates DEHP, DNOP, DINP, and DIDP compared to short chain phthalates such as DMP and DBP. The Dock score and Glide score values were also higher for long chain phthalates compared to short chain phthalates. Hence, overlapping of interacting amino acid residues between phthalate compounds and natural ligand, dihydrotestosterone, suggested potential disrupting activity of phthalates in the endocrine homeostasis function of SHBG, with long chain phthalates expected to be more potent than the short chain phthalates.
| S-EPMC4786149 | biostudies-literature
Project description:BackgroundPrenatal exposures to phthalates and bisphenols are associated with impaired brain development in animals. However, epidemiological studies investigating the association between prenatal phthalate or bisphenol exposure and cognition have produced mixed findings and mostly had modest sample sizes and measured the exposure during the third trimester.ObjectiveWe examined the association between pregnancy maternal urinary biomarkers of phthalate or bisphenol exposure and nonverbal intelligence quotient (IQ) in children 6 years of age.MethodThe study sample consisted of 1,282 mother-child pairs participating in the Generation R Study, a population-based birth cohort in Rotterdam, Netherlands (enrollment 2002-2006). We measured maternal urinary concentrations of 18 phthalate metabolites and 8 bisphenols at <18, 18-25, and >25 wks of gestation. Child nonverbal IQ was measured at 6 years of age using the Snijders-Oomen Nonverbal Intelligence Test-Revised. Linear regression models were fit for each of the three collection phases separately, the three collection phases jointly, and for the averaged prenatal exposure across pregnancy.ResultsHigher urinary concentrations of phthalate metabolites during early pregnancy were associated with lower child nonverbal IQ score [e.g., B per 10-fold increase in summed low-molecular weight phthalates=-1.7 (95% CI: -3.1, -0.3)]. This association remained unchanged when adjusted for mid and late pregnancy exposures. We also observed an inverse association between late pregnancy di-n-octyl phthalate (DNOP) exposure and nonverbal IQ. Maternal urinary concentrations of bisphenols were not associated with child nonverbal IQ. There was no effect estimate modification by sex.ConclusionsWe did not observe that maternal biomarkers of bisphenol exposure are associated with nonverbal IQ. We found that phthalate exposure in early pregnancy and DNOP exposure in late pregnancy are associated with lower nonverbal IQ scores in children. Our results might suggest that particularly early pregnancy is a sensitive window of phthalate exposure, but future studies are needed to replicate our findings. https://doi.org/10.1289/EHP6047.
| S-EPMC7384796 | biostudies-literature
Project description:IntroductionPregnant women often underreport their smoking status and extent of secondhand smoke (SHS) exposure. Biomarker confirmation is the recommended method to assess smoking behaviors and SHS exposure in both mothers and infants.ObjectivesThe primary aims are to (a) examine the relationship between smoking behaviors and SHS exposure in mother-baby couplets using maternal and infant hair nicotine and maternal urine cotinine analyses and (b) determine whether there is an association between maternal and infant hair nicotine samples obtained shortly after birth.DiscussionA cross-sectional study with a multiethnic sample of 210 mother-baby couplets assessing SHS exposure.ResultsThe level of maternal hair nicotine (MHN) was significantly different among three groups: nonsmoking, nonsmoking/passive exposed, and smoking (p < .0001), with nonsmoking and nonexposed women having the lowest level. Urine cotinine was strongly associated with self-reported smoking status (rho = .88; p < .0001). Maternal and infant hair nicotine were correlated, although MHN correlated more strongly with smoking status (rho = .46, p < .0001) than infant hair nicotine (rho = .39, p < .0001).ConclusionsMHN was a more precise biomarker of prenatal SHS exposure than infant hair nicotine; mothers' urine cotinine was strongly correlated with self-reported smoking status.
| S-EPMC2816196 | biostudies-literature
Project description:BACKGROUND:Phthalate exposure is widespread. Prior research suggests that prenatal phthalate exposure may influence birth size and gestational duration, but published results have been inconsistent. OBJECTIVE:We quantified the relationship between maternal urinary phthalate concentrations and infant birth weight z-scores, length, head circumference, and gestational duration. METHODS:In a cohort of 368 women from the HOME Study, based in Cincinnati, OH, we measured nine phthalate metabolites representing exposure to six parent phthalate diesters in urine collected at approximately 16 and 26 weeks gestation. Infant birth size and gestational duration were abstracted from medical records. We used multivariable linear regression to estimate covariate adjusted associations between urinary phthalate metabolite concentrations and infant outcomes. RESULTS:In unadjusted models, we observed a negative association between monoethyl phthalate (MEP) and birth weight z-scores, while mono-3-carboxypropyl phthalate (MCPP) was positively associated with gestational duration. After covariate adjustment, phthalate metabolite concentrations were no longer associated with birth size or gestational duration. CONCLUSIONS:In this cohort, urinary phthalate metabolite concentrations during pregnancy were not associated with infant birth size or gestational duration. Additional research is needed to determine if exposures during earlier periods of fetal development are associated with infant health.
| S-EPMC5003714 | biostudies-literature