Endocrine Disrupting Chemicals In Relation Research Articles

Diabetes mellitus: Plasticizers and nanomaterials acting as endocrine-disrupting chemicals (Review).

Various plasticizers and nanomaterials have been linked to endocrine disruptors or endocrine-disrupting chemicals (EDCs) which represent a large, heterogeneous, yet incompletely understood group of structures acting on normal and pathological body pathways such as hormonal production, secretion, transport and receptor binding. By contrast, various applications of nanoparticles are currently under investigation since the delivery of useful drugs, particularly insulin in diabetes mellitus, is essential in case of insulin deficiency. The aim of the present review was to introduce and examine different plasticizers and nanomaterials with potential applications for diabetic patients (such as selenium or gold-based nanoparticles that help the oral delivery of insulin) or plasticizers/nanomaterials acting similarly to EDCs in relation to the human and animal body, particularly glucose metabolism impairment such as diabetes mellitus (DM). Bisphenol A is a chemical used worldwide; however, the effect of exposure varies with regard to the source, environment, time of exposure and the age of the organism. Daily exposure is mostly related to food and drinks stored in polycarbonate plastics. However, exposure may also be through the skin or through the maternal placenta or breast milk which are risk factors for the fetus and for the newborn. It exerts an estrogen-like profile, but it also induces insulin resistance by impairing peripheral insulin receptors or it decreases insulin secretion by acting at the level of insulin-secreting pancreatic β-cells. Phthalates, compounds of flexible plastics, act as EDCs via their human metabolites such as diethyl phthalate and derivative monoethyl phthalate. Their role in inducing gestational DM and weight gain/obesity during pregnancy has been showcased. The vast field of plasticizers and nanomolecules acting as endocrine disruptors is widely linked to clinical aspects of DM, a serious condition with a major population impact. The importance of understanding and using these agents and applications is reflected in saving numerous human lives.

A multi-pollutant assessment of preconception persistent endocrine disrupting chemicals and incident pregnancy loss.

A few endocrine disrupting chemicals (EDCs) have been associated with pregnancy loss often as reported by women, though there has been no study of EDC mixtures and pregnancy loss in keeping with the nature of human exposure. To investigate preconception exposure to a mixture of EDCs to identify important drivers and inform multi-pollutant models of EDCs in relation to incident human gonadrophin chorionic (hCG) pregnancy loss. A cohort of 501 couples were recruited from the general population and prospectively followed until a hCG-confirmed pregnancy or 12months of trying to become pregnant. Pregnant (n=344; 69%) women were followed daily through seven weeks post-conception then monthly until delivery. Loss was defined as conversion to negative pregnancy test or a clinical diagnosis. Preconception exposure assessment of EDCs included sixty-three serum chemicals and three blood metals. EDCs were measured using isotope dilution gas chromatography-high resolution mass spectrometry or high-performance liquid chromatography-tandem mass spectrometry, and inductively coupled plasma-mass spectrometry, respectively. Using elastic net variable selection to identify important factors from the exposure mixture, EDC levels and covariates were then included in Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of time-to-pregnancy loss in multi-pollutant models. Incidence of hCG pregnancy loss was 28%. Nine EDCs of the sixty-six chemical mixture were associated with pregnancy loss; HRs were elevated for polychlorinated biphenyl 194, 2-(N-methyl-perfluorooctane sulfonamido) acetate, polybrominated diphenyl ether 28, and cadmium, even in sensitivity models adjusting for male partners' EDC concentrations. In final multivariable multi-pollutant Cox proportional hazard models, female partners'polybrominated diphenyl ether 28 (aHR=1.16, 95% CI: 1.02, 1.31) and cadmium (aHR=1.23, 95% CI: 1.07, 1.40) remained associated with hCG pregnancy loss. Female partners' preconception serum polychlorinated biphenyl 194 and 2-(N-methyl-perfluorooctane sulfonamido) acetate concentrations were consistently inversely associated with loss [(aHR=0.72, 95% CI: 0.56, 0.92) and (aHR=0.79, 95% CI: 0.65, 0.95), respectively]. Assessing exposure to a mixture of 66 persistent EDCs, females' preconception concentrations of polybrominated diphenyl ether 28 and cadmium were positively associated with incident hCG pregnancy loss in a cohort of couples from the general population trying for pregnancy.

Identifying windows of susceptibility to endocrine disrupting chemicals in relation to gestational weight gain among pregnant women attending a fertility clinic

BackgroundExposure to endocrine disrupting chemicals (EDC), such as phthalates and phenols, during pregnancy may be associated with excessive gestational weight gain (GWG), an important predictor of future health of the mother and the offspring. There is however a paucity of literature examining this association, and no study has accounted for the complex nature of EDCs exposure as a time-varying mixture of chemicals. ObjectiveWe examined the association between trimester-specific EDCs mixture and GWG in pregnant women attending a fertility clinic, to identify windows of susceptibility to such exposures, and assess the individual contribution of each chemical over pregnancy. MethodsWe included 243 pregnant women from the Environment and Reproductive Health (EARTH) Study, who provided up to 3 urine samples (one per trimester), and with available data on GWG. Urinary concentrations of 7 phthalate metabolites, bisphenol A, and 2 parabens, corrected for specific gravity, were included in the analysis. The association between trimester-specific EDCs mixture and GWG was evaluated using multiple regression models – categorizing exposures into concentration quartiles– and with Bayesian Kernel Machine Regression (BKMR), while adjusting for potential confounders. Hierarchical BKMR (hBKMR) was used to account for the time-varying nature of chemical concentrations over pregnancy, identifying the most important trimester and most important EDC within each trimester. ResultsDuring 1st trimester, higher GWG was observed at higher sum of metabolites of di (2-ethylhexyl) phthalate (ΣDEHP) from both multiple regression (e.g. comparing the 4th quartile with the 1st: β = 2.36 kg, 95% CI: 0.47, 5.19) and BKMR. During 2nd and 3rd trimesters, positive associations with mono-n-butyl phthalate and propylparaben, and negative with ΣDEHP and methylparaben were observed. When evaluating exposures as a time-varying mixture with hBKMR, 1st trimester was the most important exposure window when evaluating prenatal urinary EDCs in relation to GWG. Within the 1st trimester, urinary ΣDEHP, mono-isobutyl phthalate and propylparaben had the highest contribution in the positive association between the mixture and GWG. ConclusionWe observed positive associations between urinary EDCs during pregnancy, especially DEHP metabolites, and GWG. Our results suggest the 1st trimester of pregnancy as the time window of highest susceptibility to the effects of EDCs on GWG, with potential indication for the design of public health interventions, informing prevention strategies for reducing sources of exposure at specific time points.

Abstract PO-163: Pre-diagnostic phthalates and other endocrine disruptors in relation to endometrial cancer risk in the Multiethnic Cohort (MEC) Study

Abstract Introduction: Endometrial cancer develops under conditions of high circulating estrogen levels unopposed by progesterone. We hypothesized that exposure to endocrine disrupting chemicals (EDCs), including those that are used in plastics such as phthalates, will increase endometrial cancer risk and may contribute to racial/ethnic differences in risk. Methods: We conducted a case-control study nested in the Multiethnic Cohort (MEC) Study to measure EDCs in pre-diagnostic urine samples. We identified 139 postmenopausal endometrial cancer cases and 139 female controls matched on race/ethnicity, study site, birth year, fasting hours, urine type, date/time of urine collection and current menopausal hormone therapy use. Concentrations of 17 EDCs including urinary phthalates, bisphenol A, parabens and triclosan were measured by highly sensitive liquid chromatography high-resolution accurate-mass mass spectrometry in the UHCC Analytical Biochemistry Shared Resource using validated published protocols. Creatinine-adjusted urinary EDC excretion values were divided into tertiles based on the distribution in controls. Conditional logistic regression, with matched sets used as strata, was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for the association between EDC levels and endometrial cancer risk accounting for body mass index (BMI), diabetes, and the Mediterranean Diet Score. Results: The median (Q25, Q75) time between urine collection and endometrial cancer diagnosis was 6.6 years (3.4, 9.4). Fifty-two case-control sets were Japanese American, 35 were White, 26 were Native Hawaiian, 17 were Latina and nine were African American. In analyses of the full population, the butyl phthalate metabolite monoisobutyl phthalate (MIBP) was suggestively associated with endometrial cancer risk (tertile 3 (T3) vs. T1, OR 2.07 [CI 0.96-4.47]). This association was stronger in non-whites (n=104 case-sets; T3 vs. T1, OR 3.11 [CI 1.17-8.27]), who are thought to be exposed to higher levels of selected EDCs. We also observed a non-significant positive association among non-whites for mono n-butyl phthalate (MBP; T3 vs. T1, OR 2.55 [CI 0.90-7.22]). Conclusion: To our knowledge this is the first study to examine the role of several EDCs in relation to endometrial cancer risk using pre-diagnostic samples. These data suggest that exposure to di-butyl phthalates, which were observed in vitro to be weakly estrogenic in mammalian estrogen screens (Jobling et al., 1995, Environ Health Perspect, 103: 582-7), may represent a risk factor for endometrial cancer among non-white women that is independent of BMI and diabetes status. Replication of these findings in other large cohort studies is warranted, especially in non-whites. Citation Format: Danja Sarink, Loïc Le Marchand, Iona Cheng, Anna H. Wu, Adrian A. Franke, Lynne R. Wilkens, Kami K. White, Herbert Yu, Melissa A. Merritt. Pre-diagnostic phthalates and other endocrine disruptors in relation to endometrial cancer risk in the Multiethnic Cohort (MEC) Study [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-163.

Endocrine Disrupting Chemical Mixtures Alter Maternal Thyroid Hormones - A Potential Pathway for Altered Fetal Programming?

Background: During early pregnancy the fetus wholly depends on maternal thyroid hormone (TH) for normal growth and development. Even sub-clinical changes can elicit adverse pregnancy and child-health outcomes. Individually, numerous endocrine disrupting chemicals (EDCs) have been linked to altered TH levels, but the combined effect of multiple EDCs remains understudied. Aim: To evaluate the cross-sectional association between 26 suspected or confirmed EDCs measured in urine and blood on maternal TH status during the first trimester of pregnancy. Methods: Within the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study, we assessed EDCs in relation to thyroid function markers, including thyroxine and free and total triiodothyronine (fT3, tT3), among 1240 pregnant women (median 10 weeks gestation) using Weighted Quantile Sum (WQS) regression. We tested bi-directional constraints, adjusting for maternal age, ethnicity, education, parity, smoking, gestational age, thyroglobulin and thyroid-peroxidase antibodies, and urinary creatinine. Based on prior literature, we assessed interactions by gestational age. Results: The EDC mixture was related to lower fT3 levels (WQS=-0.21 95%CI=-0.29, -0.13); the largest chemical weights included total polychlorinated biphenyls (PCBs) (25%), trans-nonachlor (17%), and dichlorodiphenyltrichloroethane (DDT) (10%). The EDC mixture was related to altered fT3, with different chemicals eliciting positive and negative effects. The negatively constrained estimate (WQS=-0.12 95%CI=-0.19, -0.04) was driven by PCBs (17%), DDT (13%), and perfluorooctane sulfonate (PFOS) (13%), whereas the positively constrained estimate (WQS=0.08 95%CI=0.01, 0.15) was driven by 2-4-methyl-7-oxyooctyl-oxycarbonyl-cyclohexane-carboxylic-acid (MOiNCH) (13%), 2-hydroxyphenanthrene (12%), and monoethyl and monobutyl phthalates (MEP, MBP) (11%, 11%). With a negative constraint, there was a significant interaction between the EDC mixture and gestational age for fT3 (WQSxAge=-0.03 95%CI=-0.01, -0.05). Conclusions: During pregnancy, mixtures of persistent chlorinated and perfluoroalkyl compounds were related to lower tT3 and fT3, whereas short-lived pollutants (plasticizers, polycyclic aromatic hydrocarbon) were related to higher fT3. Detected associations may depend on gestational age.

Effects of sodium perchlorate and exogenous L‐thyroxine on growth, development and leptin signaling pathway of Bufo gargarizans tadpoles during metamorphosis

Sodium perchlorate (NaClO4) and exogenous L‐thyroxine (T4), two kinds of endocrine-disrupting chemicals (EDCs), mainly affect the circulating thyroid hormones, which regulate the initiation and rate of metamorphosis in amphibian. The aim of this study is to evaluate the potential role of EDCs in regulating the development of tadpoles and leptin signaling pathway of liver during the metamorphosis of Bufo gargarizans. There was completely opposite result of average development stage of tadpoles and morphological parameters between the NaClO4 and T4 exposure groups. Histological analysis revealed that NaClO4 and T4 exposure both caused liver injury, such as the decreased size of hepatocytes, atrophy of nucleus, increased melanomacrophage centres and disappearance of hepatocyte membranes. In addition, the results of RT-qPCR revealed that NaClO4 treatment significantly inhibited the transcript levels of genes related to thyroid hormone (D2, TRα and TRβ) and leptin signaling pathway (LepR, JAK1, JAK2, and TYK2), while there was an increase of mRNA expression of these genes in the liver of tadpoles administrated with T4 compared with control. This work lays an important foundation for assessing the risk of EDCs in relation to amphibian development during metamorphosis.

Prenatal Exposure to Endocrine-disrupting Chemicals in Relation to Autism Spectrum Disorder and Intellectual Disability.

Exposure to endocrine disruptors is unavoidable. Many such compounds are suspected to impact neurologic development of children, but most studies conducted have considered effects of individual chemicals in isolation. Because exposures co-occur, it is important to consider their health impacts in a single regression framework. We applied Bayesian statistical tools (including shared mean and mixture priors for 25 unique chemicals) to study independent associations of endocrine disruptor biomarkers with autism spectrum disorder (ASD) (n = 491) and intellectual disability (n = 155), compared with 373 general population controls, in the Early Markers for Autism study. We measured biomarkers in maternal serum collected and stored from midpregnancy and considered them individually or as a class (i.e., summed polychlorinated biphenyls). We adjusted all models for original matching factors (child sex and month and year of birth), maternal age, maternal race/ethnicity, parity, and maternal education at the time samples were collected. We estimated the change in the odds of ASD or intellectual disability per 1 SD increase in the z-score of measured biomarker concentration for each chemical. Odds of ASD and intellectual disability did not change with increasing concentration for any specific endocrine disruptor. The effect estimates for each chemical were centered on or near an odds ratio of 1.00 in both models where we applied a shared mean or a mixture prior. Our mixtures analyses do not suggest an independent relationship with ASD or intellectual disability with any of the 25 chemicals examined together in this mixtures analysis.