Maternal occupational exposure to endocrine-disrupting chemicals and urogenital anomalies in the offspring.
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ABSTRACT:
SUBMITTER: Spinder N
PROVIDER: S-EPMC8730314 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Endocrine-disrupting chemicals (EDCs) can act upon a developing organism to change its endocrine health and behavior in adulthood. Beyond actions on the exposed individuals, transgenerational effects of several EDCs have been reported. This study assessed the combinatorial impact of EDC-altered maternal care and transgenerational inheritance on F3 male and female offspring. Pregnant rats were exposed to EDCs with different modes of action: the weakly estrogenic polychlorinated biphenyl (PCB) mixture Aroclor 1221, the anti-androgenic fungicide vinclozolin (VIN), or the vehicle (6% dimethylsulfoxide in sesame oil; VEH) during embryonic development. The F1 male and female offspring were bred through the paternal- or maternal-lineage with untreated partners to generate F2 offspring. This process was repeated through both maternal and paternal lineages to create the F3 generation. Maternal care of F2 dams towards their F3 offspring was altered in a lineage-dependent manner, particularly in PCB paternal-lineage animals. When F3 pups were recorded for ultrasonic vocalizations (USVs) following separation from the mother, the rate of neonatal USVs in F3 offspring were decreased in PCB paternal-lineage pups. In adulthood, anxiety-like behaviors of the F3 rats were tested, with only small effects of EDCs detected. These interactions of maternal behaviors and EDC effects across generations, especially via the paternal lineage, has implications for health and environmental responses in wildlife and humans.
| S-EPMC6366859 | biostudies-literature
Project description:Women of reproductive age can be exposed to endocrine-disrupting chemicals (EDCs) at work, and exposure to EDCs in pregnancy may affect fetal growth.We assessed whether maternal occupational exposure to EDCs during pregnancy as classified by application of a job exposure matrix was associated with birth weight, term low birth weight (LBW), length of gestation, and preterm delivery.Using individual participant data from 133,957 mother-child pairs in 13 European cohorts spanning births from 1994 through 2011, we linked maternal job titles with exposure to 10 EDC groups as assessed through a job exposure matrix. For each group, we combined the two levels of exposure categories (possible and probable) and compared birth outcomes with the unexposed group (exposure unlikely). We performed meta-analyses of cohort-specific estimates.Eleven percent of pregnant women were classified as exposed to EDCs at work during pregnancy, based on job title. Classification of exposure to one or more EDC group was associated with an increased risk of term LBW [odds ratio (OR) = 1.25; 95% CI: 1.04, 1.49], as were most specific EDC groups; this association was consistent across cohorts. Further, the risk increased with increasing number of EDC groups (OR = 2.11; 95% CI: 1.10, 4.06 for exposure to four or more EDC groups). There were few associations (p < 0.05) with the other outcomes; women holding job titles classified as exposed to bisphenol A or brominated flame retardants were at higher risk for longer length of gestation.Results from our large population-based birth cohort design indicate that employment during pregnancy in occupations classified as possibly or probably exposed to EDCs was associated with an increased risk of term LBW. Citation: Birks L, Casas M, Garcia AM, Alexander J, Barros H, Bergström A, Bonde JP, Burdorf A, Costet N, Danileviciute A, Eggesbø M, Fernández MF, González-Galarzo MC, Gražulevi?ien? R, Hanke W, Jaddoe V, Kogevinas M, Kull I, Lertxundi A, Melaki V, Andersen AM, Olea N, Polanska K, Rusconi F, Santa-Marina L, Santos AC, Vrijkotte T, Zugna D, Nieuwenhuijsen M, Cordier S, Vrijheid M. 2016. Occupational exposure to endocrine-disrupting chemicals and birth weight and length of gestation: a European meta-analysis. Environ Health Perspect 124:1785-1793; http://dx.doi.org/10.1289/EHP208.
| S-EPMC5089886 | biostudies-other
Project description:Previous studies suggest that periconceptional maternal occupational exposure to solvents and pesticides increase the risk of oral clefts in the offspring. Less is known about the effect of occupational exposure to metals, dust, and gases and fumes on development of oral clefts.This case-malformed control study used data from a population-based birth defects registry (Eurocat) of children and foetuses born in the Northern Netherlands between 1997 and 2013. Cases were defined as non-syndromic oral clefts. The first control group had chromosomal/monogenic defects, and the second control group was defined as non-chromosomal/non-monogenic malformed controls. Maternal occupational exposure was estimated through linkage of mothers' occupation with a community-based Job Exposure Matrix (JEM). Multivariate logistic regression was used to estimate the effect of occupational exposures. Odds ratios were adjusted (aORs) for relevant confounders.A total of 387 cases, 1135 chromosomal and 4352 non-chromosomal malformed controls were included in this study. Prevalence of maternal occupational exposures to all agents was 43.9% and 41.0%/37.7% among cases and controls, respectively. Oral clefts had significantly increased ORs of maternal occupational exposure to pesticides (aOR = 1.7, 95% confidence interval [CI] 1.0-3.1) and dust (aOR = 1.3, 95% CI 1.1-1.6) when using non-chromosomal controls. Subgroup analysis for CL(P) stratified by gender showed a significantly increased risk for male infants exposed to 'other solvents' and exposure to mineral dust for female infants.Our study showed that maternal occupational exposure to pesticides and dust are risk factors for oral clefts in the offspring. Larger studies are needed to confirm this finding.
| S-EPMC5545025 | biostudies-other
Project description:Humans are increasingly and consistently exposed to a variety of endocrine disrupting chemicals (EDCs), chemicals that have been linked to neurobehavioral disorders such as ADHD and autism. Many of such EDCs have been shown to adversely influence brain mesocorticolimbic systems raising the potential for cumulative toxicity. As such, understanding the effects of developmental exposure to mixtures of EDCs is critical to public health protection. Consequently, this study compared the effects of a mixture of four EDCs to their effects alone to examine potential for enhanced toxicity, using behavioral domains and paradigms known to be mediated by mesocorticolimbic circuits (fixed interval (FI) schedule controlled behavior, novel object recognition memory and locomotor activity) in offspring of pregnant mice that had been exposed to vehicle or relatively low doses of four EDCs, atrazine (ATR - 10mg/kg), perfluorooctanoic acid (PFOA - 0.1mg/kg), bisphenol-A (BPA - 50 ?g/kg), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD - 0.25 ?g/kg) alone or combined in a mixture (MIX), from gestational day 7 until weaning. EDC-treated males maintained significantly higher horizontal activity levels across three testing sessions, indicative of delayed habituation, whereas no effects were found in females. Statistically significant effects of MIX were seen in males, but not females, in the form of increased FI response rates, in contrast to reductions in response rate with ATR, BPA and TCDD, and reduced short term memory in the novel object recognition paradigm. MIX also reversed the typically lower neophobia levels of males compared to females. With respect to individual EDCs, TCDD produced notable increases in FI response rates in females, and PFOA significantly increased ambulatory locomotor activity in males. Collectively, these findings show the potential for enhanced behavioral effects of EDC mixtures in males and underscore the need for animal studies to fully investigate mixtures, including chemicals that converge on common physiological substrates to examine potential mechanisms of toxicity with full dose effect curves to assist in interpretations of relevant mechanisms.
| S-EPMC4387783 | biostudies-literature
Project description:A growing epidemic of nonalcoholic fatty liver disease (NAFLD) is paralleling the increase in the incidence of obesity and diabetes mellitus in countries that consume a Western diet. As NAFLD can lead to life-threatening conditions such as cirrhosis and hepatocellular carcinoma, an understanding of the factors that trigger its development and pathological progression is needed. Although by definition this disease is not associated with alcohol consumption, exposure to environmental agents that have been linked to other diseases might have a role in the development of NAFLD. Here, we focus on one class of these agents, endocrine-disrupting chemicals (EDCs), and their potential to influence the initiation and progression of a cascade of pathological conditions associated with hepatic steatosis (fatty liver). Experimental studies have revealed several potential mechanisms by which EDC exposure might contribute to disease pathogenesis, including the modulation of nuclear hormone receptor function and the alteration of the epigenome. However, many questions remain to be addressed about the causal link between acute and chronic EDC exposure and the development of NAFLD in humans. Future studies that address these questions hold promise not only for understanding the linkage between EDC exposure and liver disease but also for elucidating the molecular mechanisms that underpin NAFLD, which in turn could facilitate the development of new prevention and treatment opportunities.
| S-EPMC5657429 | biostudies-other
Project description:ContextSteroids play an important role in fetal development and parturition. Gestational exposures to endocrine-disrupting chemicals (EDCs) affect steroidal milieu and pregnancy outcomes, raising the possibility of steroids serving as biomarkers. Most studies have not addressed the impact of EDC mixtures, which are reflective of real life scenarios.ObjectiveAssess the association of maternal and neonatal steroids with pregnancy outcomes and early pregnancy EDC levels.DesignProspective analysis of mother-infant dyads.SettingUniversity hospital.Participants121 mother-infant dyads.Main outcome measuresThe associations of maternal and neonatal steroidal hormones from 121 dyads with pregnancy outcomes, the associations of first trimester EDCs individually and as mixtures with maternal and neonatal steroids in a subset of 56 dyads and the influence of body mass index (BMI), age, and offspring sex in modulating the EDC associations with steroids were determined.ResultsSteroid-specific positive or negative associations with pregnancy measures were evident; many maternal first trimester EDCs were negatively associated with estrogens and positively with androgen/estrogen ratios; EDC-steroid associations were influenced by maternal age, pre-pregnancy BMI, and fetal sex; and EDCs individually and as mixtures showed direct and inverse fetal sex-dependent associations with maternal and neonatal steroids.ConclusionsThis proof-of-concept study indicates association of steroids with pregnancy outcomes depending on maternal age, prepregnancy BMI, and fetal sex, with the effects of EDCs differing when considered individually or as mixtures. These findings suggest that steroidal hormonal measures have potential to serve as biomarkers of impact of EDC exposures and pregnancy outcome.
| S-EPMC7947779 | biostudies-literature
Project description:Since reports published in 2015 and 2016 identified 15 probable exposure-outcome associations, there has been an increase in studies in humans of exposure to endocrine-disrupting chemicals (EDCs) and a deepened understanding of their effects on human health. In this Series paper, we have reviewed subsequent additions to the literature and identified new exposure-outcome associations with substantial human evidence. Evidence is particularly strong for relations between perfluoroalkyl substances and child and adult obesity, impaired glucose tolerance, gestational diabetes, reduced birthweight, reduced semen quality, polycystic ovarian syndrome, endometriosis, and breast cancer. Evidence also exists for relations between bisphenols and adult diabetes, reduced semen quality, and polycystic ovarian syndrome; phthalates and prematurity, reduced anogenital distance in boys, childhood obesity, and impaired glucose tolerance; organophosphate pesticides and reduced semen quality; and occupational exposure to pesticides and prostate cancer. Greater evidence has accumulated than was previously identified for cognitive deficits and attention-deficit disorder in children following prenatal exposure to bisphenol A, organophosphate pesticides, and polybrominated flame retardants. Although systematic evaluation is needed of the probability and strength of these exposure-outcome relations, the growing evidence supports urgent action to reduce exposure to EDCs.
| S-EPMC7437820 | biostudies-literature
Project description:BackgroundToxicology studies have identified pregnancy as a window of susceptibility for endocrine disrupting chemicals (EDCs) and cardiometabolic indices in women. No study in humans, however, has examined EDC mixtures and cardiometabolic indices during pregnancy.MethodsWe used the Health Outcomes and Measures of the Environment (HOME) Study to examine whether bisphenol A (BPA), polybrominated diphenyl ethers (PBDEs), per- and polyfluoroalkyl substances (PFAS), and phthalates are associated with blood pressure, glucose, and lipids in 388 pregnant women. We measured PBDEs and PFAS in serum at 16 weeks gestation, while BPA and phthalate metabolites were quantified in urine at 16 and 26 weeks gestation. We used linear regression and Bayesian Kernel Machine Regression (BKMR) to estimate covariate-adjusted associations of individual EDCs and their mixtures with cardiometabolic indices during pregnancy.ResultsA 10-fold increase in BDE-28 was associated with a 13.1 mg/dL increase in glucose (95% Confidence Interval [CI] 2.9, 23.2) in linear regression. The BKMR model also identified BDE-28 as having a positive association with glucose. BDE-28, BDE-47, and BDE-99 were positively associated with total cholesterol in both single- and multi-pollutant models, whereas a suggestive negative association was noted with BDE-153. Mono-n-butyl phthalate (MBP) (β = -7.9 mg/dL, 95% CI -12.9, -3.0) and monobenzyl phthalate (MBzP) (β = -6.3 mg/dL, 95% CI -10.6, -2.0) were both associated with significant decreases in cholesterol in linear regression, but only MBzP was identified as an important contributor in the BKMR model.ConclusionOverall, we observed positive associations between PBDEs with glucose and cholesterol levels during pregnancy, while negative associations were found between some phthalate biomarkers and cholesterol. No relationship was noted for BPA or PFAS with cardiometabolic indices during pregnancy across both models.
| S-EPMC8393591 | biostudies-literature
Project description:The emerging field of omics - large-scale data-rich biological measurements of the genome - provides new opportunities to advance and strengthen research into endocrine-disrupting chemicals (EDCs). Although some EDCs have been associated with adverse health effects in humans, our understanding of their impact remains incomplete. Progress in the field has been primarily limited by our inability to adequately estimate and characterize exposure and identify sensitive and measurable outcomes during windows of vulnerability. Evolving omics technologies in genomics, epigenomics and mitochondriomics have the potential to generate data that enhance exposure assessment to include the exposome - the totality of the lifetime exposure burden - and provide biology-based estimates of individual risks. Applying omics technologies to expand our knowledge of individual risk and susceptibility will augment biological data in the prediction of variability and response to disease, thereby further advancing EDC research. Together, refined exposure characterization and enhanced disease-risk prediction will help to bridge crucial gaps in EDC research and create opportunities to move the field towards a new vision - precision public health.
| S-EPMC7141602 | biostudies-literature
Project description:Much of the early work on Nuclear Hormone Receptors (NHRs) focused on their essential roles as mediators of sex steroid hormone signaling in reproductive development and function, and thyroid hormone-dependent formation of the central nervous system. However, as NHRs display tissue-specific distributions and activities, it is not surprising that they are involved and vital in numerous aspects of human development and essential for homeostasis of all organ systems. Much attention has recently been focused on the role of NHRs in energy balance, metabolism, and lipid homeostasis. Dysregulation of NHR function has been implicated in numerous pathologies including cancers, metabolic obesity and syndrome, Type II diabetes mellitus, cardiovascular disease, hyperlipidemia, male and female infertility and other reproductive disorders. This review will discuss the dysregulation of NHR function by environmental endocrine disrupting chemicals (EDCs), and the associated pathological consequences of exposure in numerous tissues and organ systems, as revealed by experimental, clinical, and epidemiological studies.
| S-EPMC7016921 | biostudies-literature