Maternal Polychlorinated Biphenyls Levels Research Articles

Networks of placental DNA methylation correlate with maternal serum PCB concentrations and child neurodevelopment

BackgroundGestational exposure to polychlorinated biphenyls (PCBs) has been associated with elevated risk for neurodevelopmental disorders. Placental epigenetics may serve as a potential mechanism of risk or marker of altered placental function. Prior studies have associated differential placental DNA methylation with maternal PCB exposure or with increased risk of autism spectrum disorder (ASD). However, sequencing-based placental methylomes have not previously been tested for simultaneous associations with maternal PCB levels and child neurodevelopmental outcomes. ObjectivesWe aimed to identify placental DNA methylation patterns associated with maternal PCB levels and child neurodevelopmental outcomes in the high-risk ASD MARBLES cohort. MethodsWe measured 209 PCB congeners in 104 maternal serum samples collected at delivery. We identified networks of DNA methylation from 147 placenta samples using the Comethyl R package, which performs weighted gene correlation network analysis for whole genome bisulfite sequencing data. We tested placental DNA methylation modules for association with maternal serum PCB levels, child neurodevelopment, and other participant traits. ResultsPCBs 153 + 168, 170, 180 + 193, and 187 were detected in over 50% of maternal serum samples and were highly correlated with one another. Consistent with previous findings, maternal age was the strongest predictor of serum PCB levels, alongside year of sample collection, pre-pregnancy BMI, and polyunsaturated fatty acid levels. Twenty seven modules of placental DNA methylation were identified, including five which significantly correlated with one or more PCBs, and four which correlated with child neurodevelopment. Two modules associated with maternal PCB levels as well as child neurodevelopment, and mapped to CSMD1 and AUTS2, genes previously implicated in ASD and identified as differentially methylated regions in mouse brain and placenta following gestational PCB exposure. ConclusionsPlacental DNA co-methylation modules were associated with maternal PCBs and child neurodevelopment. Methylation of CSMD1 and AUTS2 could be markers of altered placental function and/or ASD risk following maternal PCB exposure.

Maternal Exposure to Polychlorinated Biphenyls and Asthma, Allergic Rhinitis and Atopic Dermatitis in the Offspring: The Environmental Health Fund Birth Cohort.

Background: Polychlorinated biphenyls (PCBs) are persistent organic pollutants banned for use worldwide. Due to their biodegradation resistance, they accumulate along the food chain and in the environment. Maternal exposure to PCBs may affect the fetus and the infant. PCBs are immunotoxic and may damage the developing immune system. PCBs are associated with elevated IgE antibodies in cord blood and are considered to be predictive of atopic reactions. Several studies on the association between prenatal exposure to PCBs and atopic reactions were previously published, albeit with conflicting results. Objectives: To examine the association between maternal PCBs levels and atopic reactions in their offspring. Methods: During the years 2013–2015, a prospective birth cohort was recruited at the delivery rooms of Shamir Medical Center (Assaf Harofeh) and “Dana Dwek” Children’s Hospital. Four PCBs congeners were investigated: PCBs 118, 138, 153, and 180. In 2019, when children reached the age of 4–6 years, mothers were interviewed using the ISAAC questionnaire to assess symptoms of atopic reactions, including asthma, allergic rhinitis, and atopic dermatitis. Results: One hundred and fifty mother-child dyads were analyzed. No significant differences were found in the median serum PCBs concentrations of each studied congener or total PCBs for asthma, allergic rhinitis, atopic dermatitis diagnosis, or parent-reported symptoms. No association was found between exposure to total PCBs and the risk for asthma symptoms or diagnosis, adjusted to maternal age and family member with atopic condition: aOR = 0.94, 95%CI: (0.88; 0.99). No association was observed between each studied PCB congener and asthma symptoms or diagnosis. The same results were found also for other studied outcomes—allergic rhinitis and atopic dermatitis. Conclusion: Our study joins a series of previous studies that attempt to shed light on environmental exposures in utero as influencing factors for atopic conditions in children. Our results reflect the complexity of the pathophysiology of these phenomena. No relationship between maternal serum PCBs levels was demonstrated for asthma, allergic rhinitis, or atopic dermatitis. However, additional multi-participant studies, with longer, spanning into later pediatric age follow up are needed.

Increase in accumulation of polychlorinated biphenyls in offspring mouse brain via maternal coexposure to methylmercury and polychlorinated biphenyls

Methylmercury (MeHg) and polychlorinated biphenyls (PCBs) are environmentally persistent neurodevelopmental toxicants. In Japan, the most common source of human exposure is the consumption of contaminated fish and seafood. We investigated the accumulation of MeHg and PCBs in the brains of dams and offspring mice maternally exposed to MeHg and/or PCBs. Pregnant mice (C57BL/6Cr) were assigned to one of four exposure groups: control, MeHg alone (MeHg in diet at 5 mg/kg as Hg), PCB alone (Aroclor1254 by gavage at the dose of 18 mg/kg body weight/3 days) and MeHg+PCB. Levels of MeHg and PCBs were measured in the whole brains of dams and offspring mice on postnatal day 21 (PND21) and at 9 weeks of age. Total mercury, MeHg and PCB congener concentrations were determined by CVAAS, GC-ECD and HRGC/HRMS, respectively. For the mercury concentrations, there were no significant differences between MeHg alone and MeHg+PCB except for pups at 9 weeks. The maternal PCB levels were not significantly different between MeHg+PCB and PCB alone. In pup brain on PND21, MeHg+PCB resulted in a significantly higher PCB level than PCB alone. Although the levels of lightly chlorinated (= 4CBs) homologues were lower for MeHg+PCB than for PCB alone, those of highly chlorinated (>= 5CBs) homologues were significantly higher on PND21 for MeHg+PCB. The PCB composition in dams and pups shifted to higher chlorinated homologues compared with the composition of administered Aroclor1254. For these reasons, further detailed studies are necessary to clarify the interactional effects of PCB metabolism after coexposure to MeHg and PCBs.

Prenatal Exposure to Polychlorinated Biphenyls and Postnatal Growth: A Structural Analysis

Normal endocrine function in utero and early in childhood influences later height and weight attainment. Polychlorinated biphenyls (PCBs) are persistent environmental contaminants with suspected endocrine-disrupting properties. PCBs may mimic or inhibit hormone and endocrine processes based in part on their structural configuration, with non-ortho-substituted PCBs having a coplanar orientation and ortho-substituted PCBs becoming increasingly noncoplanar. Coplanar and noncoplanar PCBs have known differences in biologic effect. Animal studies link prenatal PCB exposure to adverse birth and early-life growth outcomes, but epidemiologic studies are conflicting. We examined whether prenatal exposure to PCBs, categorized by their degree of ortho-substitution, affected childhood height and weight attainment in 150 children (109 boys and 41 girls) with African-American mothers born at the Columbia-Presbyterian Hospital from 1959 through 1962. Stratifying by sex, we used regression models for repeated measures to investigate associations between maternal levels of PCBs and height and weight through 17 years of age. Maternal levels of ortho-substituted PCBs were associated with reduced weight through 17 years of age among girls but not among boys. Tri-ortho-substituted PCBs were marginally associated with increased height in boys. Although limited by sample size, our results suggest that prenatal exposure to PCBs may affect growth, especially in girls, and that ortho-substitution is an important determinant of its effect on growth.

Maternal Levels of Polychlorinated Biphenyls in Relation to Preterm and Small-for-Gestational-Age Birth

In developed countries, polychlorinated biphenyls (PCBs) are ubiquitous contaminants of the environment, including foods. Within the range of the resulting low-level exposure, associations of PCBs with lower birth weight have been observed in several studies. To examine further the association of PCBs with birth outcomes, we measured serum levels in 1034 pregnant women who were enrolled in the U.S. Collaborative Perinatal Project in 1959 to 1965 before PCB manufacturing was banned. The multivariate-adjusted odds ratio for preterm birth among those with PCB levels of >/=4 microg/L of total PCBs, compared with those with <2 microg/L, was 1.1 (95% confidence interval = 0.6-2.2); for the same exposure contrast, the odds ratio for delivering an infant who was small-for-gestational-age at birth was 1.6 (0.7-3.7). Birth weight and length of gestation were essentially unrelated to PCB level. In these data, maternal levels of PCBs during pregnancy were essentially unrelated to preterm birth, birth weight, or length of gestation. An association of PCBs with small-for-gestational-age birth was observed, but the results were inconclusive and occurred in the absence of an overall decrease in birth weight.