Mixtures Of Endocrine Disrupting Chemicals Research Articles

Effects of Environmental Enrichment on Exposure to Human-Relevant Mixtures of Endocrine Disrupting Chemicals in Zebrafish.

Fish models used for chemical exposure in toxicological studies are normally kept in barren tanks without any structural environmental enrichment. Here, we tested the combined effects of environmental enrichment and exposure to two mixtures of endocrine disrupting chemicals (EDCs) in zebrafish. Firstly, we assessed whether developmental exposure to an EDC mixture (MIX G1) combined with rearing the fish in an enriched environment influenced behaviour later in life. This was evaluated using locomotion tracking one month after exposure, showing a significant interaction effect between enrichment and the MIX G1 exposure on the measured locomotion parameters. After three months, we assessed behaviour using custom-made behaviour tanks, and found that enrichment influenced swimming activity. Control fish from the enriched environment were more active than control fish from the barren environment. Secondly, we exposed adult zebrafish to a separate EDC mixture (MIX G0) after rearing them in a barren or enriched environment. Behaviour and hepatic mRNA expression for thyroid-related genes were assessed. There was a significant interaction effect between exposure and enrichment on swimming activity and an effect of environment on latency to approach the group of conspecifics, where enriched fish took more time to approach the group, possibly indicating that they were less anxious. Hepatic gene expression of a thyroid-related gene (thrb) was significantly affected by EDC exposure, while enrichment had no discernible impact on the expression of the measured genes. In conclusion, environmental enrichment is important to consider when studying the effects of EDCs in fish.

Single and mixture effects of bisphenol A and benzophenone-3 on in vitro T helper cell differentiation

Immune homeostasis is key to guarantee that the immune system can elicit effector functions against pathogens and at the same time raise tolerance towards other antigens. A disturbance of this delicate balance may underlie or at least trigger pathologies. Endocrine disrupting chemicals (EDCs) are increasingly recognized as risk factors for immune dysregulation. However, the immunotoxic potential of specific EDCs and their mixtures is still poorly understood. Thus, we aimed to investigate the effect of bisphenol A (BPA) and benzophenone-3 (BP-3), alone and in combination, on in vitro differentiation of T helper (TH)17 cells and regulatory T (Treg) cells.Naïve T cells were isolated from mouse lymphoid tissues and differentiated into the respective TH population in the presence of 0.001–10 μM BP-3 and/or 0.01–100 μM BPA. Cell viability, proliferation and the expression of TH lineage specific transcription factors and cytokines was measured by flow cytometry and CBA/ELISA. Moreover, the transcription of hormone receptors as direct targets of EDCs was quantified by RT-PCR.We found that the highest BPA concentration adversely affected TH cell viability and proliferation. Moreover, the general differentiation potential of both TH populations was not altered in the presence of both EDCs. However, EDC exposure modulated the emergence of TH17 and Treg cell intermediate states. While BPA and BP-3 promoted the development of TH1-like TH17 cells under TH17-differentiating conditions, TH2-like Treg cells occurred under Treg polarization. Interestingly, differential effects could be observed in mixtures of the two tested compounds compared with the individual compounds. Notably, estrogen receptor β expression was decreased under TH17-differentiating conditions in the presence of BPA and BP-3 as mixture. In conclusion, our study provides solid evidence for both, the immune disruptive potential and the existence of cumulative effects of real nature EDC mixtures on T cell in vitro differentiation.

Non-persistent endocrine disrupting chemical mixtures and uterine leiomyomata in the study of environment, lifestyle and fibroids (SELF)

BackgroundResults of studies investigating associations between individual endocrine-disrupting chemicals (EDCs) and incidence of uterine leiomyomata (UL), a hormone-dependent gynecological condition, have been inconsistent. However, few studies have evaluated simultaneous exposure to a mixture of EDCs with UL incidence. MethodsWe conducted a case-cohort analysis (n = 708) of data from the Study of the Environment, Lifestyle and Fibroids (SELF), a prospective cohort study. Participants were aged 23–35 years at enrollment, had an intact uterus, and identified as Black or African American. We measured biomarker concentrations of 21 non-persistent EDCs, including phthalates, phenols, parabens, and triclocarban, in urine collected at baseline, 20-month, and 40-month clinic visits. We ascertained UL incidence and characteristics using ultrasounds at baseline and approximately every 20 months through 60 months. We used probit Bayesian Kernel Machine Regression (BKMR-P) to evaluate joint associations between EDC mixtures with cumulative UL incidence. We estimated the mean difference in the probit of UL incidence over the study period, adjusting for baseline age, education, years since last birth, parity, smoking status and body mass index. We converted probit estimates to odds ratios for ease of interpretation. ResultsWe observed that urinary concentrations of the overall EDC mixture were inversely associated with UL incidence in the overall mixtures model, with the strongest inverse associations at the 70th percentile of all biomarkers compared with their 50th percentile (odds ratio = 0.59; 95% confidence interval: 0.36, 0.96). Strongest contributors to the joint association for the mixture were bisphenol S (BPS), ethyl paraben (EPB), bisphenol F (BPF) and mono (2-ethyl-5-carboxypentyl) phthalate (MECPP), which each demonstrated inverse associations except for MECPP. There was suggestive evidence of an interaction between MECPP and EPB. ConclusionIn this prospective ultrasound study, we observed evidence of an inverse association between the overall mixture of urinary biomarker concentrations of non-persistent EDCs with UL incidence.

8-OHdG mediates the association of co-exposure to fifty-five typical endocrine-disrupting chemicals with renal function: a cross-section investigation in Southern Chinese adults.

Individual typical endocrine-disrupting chemicals (EDCs), including organophosphate triesters (OPEs), parabens, triclosan (TCS), bisphenols, benzophenones (BPs), phthalates (PAEs), and synthetic phenolic antioxidants (SPAs), are associated with renal dysfunction. However, the combined effects and underlying mechanisms of mixed EDC exposure on renal function remain unclear. Two hundred ninety-nine adult participants were enrolled in the cross-sectional survey conducted in Guangzhou, China. Urinary levels of 7 OPEs, 6 parabens, TCS, 14 bisphenols, 8 BPs, 15 PAEs, 4 SPAs, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were determined, and estimated glomerular filtration rate (eGFR) was served as the outcome index. We found elevated levels of diphenyl phosphate (DPP), bisphenol A (BPA), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-butyl phthalate (MBP) showed dose-responsive associations with eGFR decline, However, nonlinear associations were observed for bis(2-butoxyethyl) hydrogen phosphate (BBOEP), TCS, 4-hydroxybenzophenone (HBP), mono-n-pentyl phthalate (MnPP), and mono-benzyl phthalate (MBzP). The quantile-based g-computation model demonstrated that a quartile increase in the EDC mixture corresponded to a 0.383-SD decrease (95% CI - 0.658 ~ - 0.108, P = 0.007) in eGFR. Notably, BPA was identified as the primary contributor to this effect. Moreover, 8-OHdG mediated the eGFR decline associated with EDC mixtures with a mediation proportion of 25.49%. A sex-modified effect was also observed (P = 0.004), indicating that exposure to the mixture of EDC was linked to more pronounced renal dysfunction in females. Our novel findings suggest that exposure to a typical mixture of EDCs is associated with renal dysfunction in the general adult population of Southern China. Furthermore, 8-OHdG may play a role in the pathogenesis of EDC mixture-related renal dysfunction.

The silent threat and countermeasures: Navigating the mixture risk of endocrine-disrupting chemicals on pregnancy loss in China

Currently, many countries and regions worldwide face the challenge of declining population growth due to persistently low rates of female reproduction. Since 2017, China's birth rate has hit historic lows and continued to decline, with the death rate now equaling the birth rate. Concerns have emerged regarding the potential impact of environmental contaminants on reproductive health, including pregnancy loss. Endocrine-disrupting chemicals (EDCs) like phthalate esters (PAEs), bisphenol A (BPA), triclosan (TCS), and perfluoroalkyl substances (PFASs) have raised attention due to their adverse effects on biological systems. While China's 14th Five-Year Plan (2021–2025) for national economic and social development included the treatment of emerging pollutants, including EDCs, there are currently no national appraisal standards or regulatory frameworks for EDCs and their mixtures. Addressing the risk of EDC mixtures is an urgent matter that needs consideration from China's perspective in the near future. In this Perspective, we delve into the link between EDC mixture exposure and pregnancy loss in China. Our focus areas include establishing a comprehensive national plan targeting reproductive-aged women across diverse urban and rural areas, understanding common EDC combinations in women and their surrounding environment, exploring the relationship between EDCs and pregnancy loss via epidemiology, and reconsidering the safety of EDCs, particularly in mixtures and low-dose scenarios. We envision that this study could aid in creating preventive strategies and interventions to alleviate potential risks induced by EDC exposure during pregnancy in China.

Co-exposure to 55 endocrine-disrupting chemicals linking diminished sperm quality: Mixture effect, and the role of seminal plasma docosapentaenoic acid

Isolated effects of single endocrine-disrupting chemicals (EDCs) on male reproductive health have been studied extensively, but their mixture effect remains unelucidated. Previous research has suggested that consuming diet enriched in omega-3 polyunsaturated fatty acids (PUFA) might be beneficial for reproductive health, whether omega-3 PUFA could moderate the effect of EDCs mixture on semen quality remains to be explored. In this study of 155 male recruited from a reproductive health center in China, we used targeted-exposomics to simultaneously measure 55 EDCs in the urine for exposure burden. Regression analyses were restricted to highly detected EDCs (≥55%, n = 34), and those with consistently elevated risk were further screened and brought into mixture effect models (Bisphenol A, ethyl paraben, methyl paraben [MeP], benzophenone-1 [BP1], benzophenone-3, mono(3-carboxypropyl) phthalate [MCPP]). Bayesian Kernel Machine Regression (BKMR) and quantile-based g-computation (QGC) models demonstrated that co-exposure to top-ranked EDCs was related to reduced sperm total (β = −0.18, 95%CI: −0.29 – −0.07, P = 0.002) and progressive motility (β = −0.27, 95%CI: −0.43 – −0.10, P = 0.002), but not to lower semen volume. BP1, MeP and MCPP were identified as the main effect driver for deteriorated sperm motion parameters using mixture model analyses. Seminal plasma fatty acid profiling showed that high omega-3 PUFA status, notably elevated docosapentaenoic acid (DPA, C22:5n-3) status, moderated the association between MCPP and sperm motion parameters (total motility: β = 0.26, 95%CI: 0.01 – −0.51, Pinteraction = 0.047; progressive motility: β = 0.64, 95%CI: 0.23 – 1.05, Pinteraction = 0.003). Co-exposure to a range of EDCs is mainly associated with deteriorated sperm quality, but to a lesser extent on sperm quantity, high seminal plasma DPA status might be protective against the effect. Our work emphasizes the importance of exposomic approach to assess chemical exposures and highlighted a new possible intervention target for mitigating the potential adverse effect of EDCs on semen quality.

Identifying critical windows of prenatal phenol, paraben, and pesticide exposure and child neurodevelopment: Findings from a prospective cohort study

BackgroundThis study aimed to investigate how exposure to a mixture of endocrine disrupting chemicals (EDCs) during two points in pregnancy affects early childhood neurodevelopment. MethodsWe analyzed publicly-available data from a high-risk cohort of mothers and their children (2007–2014) that measured six EDCs including methyl-, ethyl- and propyl parabens (MEPB, ETPB, PRPB), Bisphenol-A (BPA), 3,5,6-trichloro-2-pyridinol (TCPy), 3-phenoxybenzoic acid (3-PBA) in prenatal urine samples during the second and third trimesters. Neurodevelopmental scores were assessed using Mullen Scales of Early Learning (MSEL) at age 3. We used mean field variational Bayes for lagged kernel machine regression (MFVB-LKMR) to investigate the association between trimester-specific co-exposure to the six EDCs and MSEL scores at age 3, stratified by sex. ResultsThe analysis included 130 children. For females, the relationship between BPA and 3PBA with MSEL score varied between the two trimesters. In the second trimester, effect estimates for BPA were null but inversely correlated with MSEL score in the third trimester. 3PBA had a negative relationship with MSEL in the second trimester and positive correlation in the third trimester. For males, effect estimates for all EDCs were in opposing directions across trimesters. MFVB-LKMR analysis identified significant two-way interaction between EDCs for MSEL scores in both trimesters. For example, in females, the MSEL scores associated with increased exposure to TCPy were 1.75 units (95%credible interval −0.04, −3.47) lower in the 2nd trimester and 4.61 (95%CI −3.39, −5.84) lower in the third trimester when PRPB was fixed at the 75th percentile compared to when PRPB was fixed at the 25th percentile. ConclusionOur study provides evidence that timing of EDC exposure within the prenatal period may impact neurodevelopmental outcomes in children. More of these varying effects were identified among females. Future research is needed to explore EDC mixtures and the timing of exposure during pregnancy to enhance our understanding of how these chemicals impact child health.

Personal Care Products, Socioeconomic Status, and Endocrine-Disrupting Chemical Mixtures in Black Women.

Personal care products (PCPs) are sources of exposure to endocrine-disrupting chemicals (EDCs) among women, and socioeconomic status (SES) may influence these exposures. Black women have inequitable exposure to EDCs from PCP use, but no study has investigated how exposure to EDCs through PCPs may vary by SES, independent of race. Using data from the Study of Environment, Lifestyle, and Fibroids, a cohort of reproductive-aged Black women (n = 751), we quantified associations between PCPs and urinary biomarker concentrations of EDC mixtures (i.e., phthalates, phenols, parabens) within SES groups, defined using k-modes clustering based on education, income, marital status, and employment. Information about PCP use and SES was collected through questionnaires and interviews. We used principal component analysis to characterize the EDC mixture profiles. Stratified linear regression models were fit to assess associations between PCP use and EDC mixture profiles, quantified as mean differences in PC scores, by SES group. Associations between PCP use and EDC mixture profiles varied by SES group; e.g., vaginal powder use was associated with a mixture of phenols among lower SES women, whereas this association was null for higher SES women. Findings suggest that SES influences PCP EDC exposure in Black women, which has implications for public health interventions.

EDC mixtures during pregnancy and body fat at 7 years of age in a Swedish cohort, the SELMA study

BackgroundSome endocrine disrupting chemicals (EDC), are “obesogens” and have been associated with overweight and obesity in children. Daily exposure to different classes of EDCs demands for research with mixtures approach. ObjectivesThis study evaluates the association, considering sex-specific effects, between prenatal exposure to EDC mixture and children's body fat at seven years of age. MethodsA total of 26 EDCs were assessed in prenatal urine and serum samples from first trimester in pregnancy from 737 mother-child pairs participating in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study. An indicator for children's “overall body fat” was calculated, using principal component analysis (PCA), based on BMI, percent body fat, waist, and skinfolds measured at seven years of age. Weighted quantile sum (WQS) regression was used to assess associations between EDC mixture and children's body fat. ResultsPrincipal component (PC1) represented 83.6 % of the variance, suitable as indicator for children's “overall body fat”, with positive loadings of 0.40–0.42 for each body fat measure. A significant interaction term, WQS*sex, confirmed associations in the opposite direction for boys and girls. Higher prenatal exposure to EDC mixture was borderline significant with more “overall body fat” for boys (Mean β = 0.20; 95 % CI: −0.13, 0.53) and less for girls (Mean β = −0.23; 95 % CI: −0.58, 0.13). Also, higher prenatal exposure to EDC mixture was borderline significant with more percent body fat (standardized score) for boys (Mean β = 0.09; 95 % CI: −0.04, 0.21) and less for girls (Mean β = −0.10 (−0.26, 0.05). The chemicals of concern included bisphenols, phthalates, PFAS, PAH, and pesticides with different patterns for boys and girls. DiscussionBorderline significant associations were found between prenatal exposure to a mixture of EDCs and children's body fat. The associations in opposite directions suggests that prenatal exposure to EDCs may present sex-specific effects on children's body fat.

Association of serum bisphenols, parabens, and triclosan concentrations with Sjögren Syndrome in the Hangzhou, China population

Exposure to endocrine-disrupting chemicals (EDCs) has been linked to various immune deficiency disorders, including autoimmune diseases like Sjögren Syndrome (SjS). However, the detrimental effects of exposure to EDCs, including bisphenols, parabens, and triclosan (TCS), on SjS have been inadequately documented. Thus, we conducted a cross-sectional study that included both healthy individuals (controls) and patients with SjS (cases). We assessed serum concentrations of bisphenol A (BPA), bisphenol S (BPS), methyl parabens (MeP), ethyl parabens (EtP), and TCS. The relationship between the five EDCs levels and the risk of SjS was also explored. Additionally, we conducted an in-depth analysis of the collective influence of these EDCs mixtures on SjS, employing a weighted quantile sum regression model. Out of the five EDCs analyzed, EtP displayed the highest mean concentration (2.80 ng/mL), followed by BPA (2.66 ng/mL) and MeP (1.99 ng/mL), with TCS registering the lowest level (0.36 ng/mL). Notably, BPS exposure was significantly positively associated with the risk of being diagnosed with SjS (with an odds ratio [OR] of 1.17, p = 0.042). No statistically significant associations with SjS were observed for BPA, MeP, EtP, and TCS (p > 0.05). And we did not observe any significant effects of the EDCs mixture on SjS. To the best of our knowledge, this study is the first to suggest that BPS may potentially increase the risk of SjS. Although no significant effects were observed between other EDCs and SjS risk, we cannot disregard the potential harm of EDCs due to their non-monotonic dose response.

Ovarian follicular fluid levels of phthalates and benzophenones in relation to fertility outcomes

BackgroundMany endocrine disrupting chemicals (EDCs), for instance phthalates and benzophenones, are associated with adverse fertility outcomes and semen quality parameters. ObjectiveTo evaluate if concentrations of selected phthalate metabolites and benzophenones measured in follicular fluid are associated with fertility outcomes (i.e., reproductive hormones, antral follicle count, detected heartbeat at gestational week 7, and live birth) and, in a supplementary study, if measured concentrations of chemicals in follicular fluid can exert biological effects on human spermatozoa. MethodsOverall, 111 couples from a fertility clinic in Denmark contributed with 155 follicular fluid samples. Concentrations of 43 metabolites from 19 phthalates and phthalate substitutes and six benzophenones were measured in follicular fluid using liquid chromatography-tandem mass spectrometry. Multiple linear and logistic regression with an applied generalized estimating equation model allowing more than one measurement per woman assessed the association between follicular EDC levels and fertility outcomes. The assessment of biological effects of individual and mixtures of EDCs on human spermatozoa was conducted through a human sperm cell based Ca2+-fluorimetric assay. ResultsBenzophenone-3 (BP-3) and seven metabolites of five phthalates were detectable in follicular fluid. Women with metabolites of dibutyl phthalate isomers in the highest tertiles had lower antral follicle count (MiBP: β = −5.35 [95 % CI: −9.06; −2.00], MnBP: β = −5.25 [95 % CI: −9.00; −2.00]) and lower odds for detecting a heartbeat at gestational week 7 (MiBP: OR = 0.35 [95 % CI: 0.14; 0.91], MnBP: OR = 0.39 [95 % CI: 0.13; 1.15]). Mixtures of the measured concentrations of BP-3 and the seven phthalate metabolites induced a small significant increase in the intracellular calcium ion concentration in human spermatozoa from healthy donors (n = 3). DiscussionPhthalate metabolites and BP-3 were detectable in follicular fluid and high concentrations of some phthalate metabolites were linked with lower chance of successful fertility treatment outcomes. Chemical mixture concentrations in follicular fluid induced a calcium response in human spermatozoa highlighting possible biological effects at physiologically relevant concentrations.

Current Evidence on the Effects of Endocrine-Disrupting Chemicals (EDCs) on Bone Growth and Health

AbstractEndocrine-disrupting chemicals (EDCs) are a heterogeneous group of natural and man-made chemicals from environmental sources that mimic natural hormones. They can have adverse effects on the morphology, physiology, growth, and development of different organs and systems, among these bone health can be affected too. EDCs work as agonists or antagonists on hormonal receptors in hormone-sensitive cells, influence gene expression by epigenetic mechanisms, stimulate or inhibit cell maturation, and affect the synthesis and metabolism of hormones. This review aims to summarize current evidence on the effects of exposure to EDCs on bone from early gestational to birth and long-term adverse effects. Single and mixtures of endocrine-disrupting chemicals can disrupt bone structure by modifying differentiation, increasing osteoclast activity, inhibiting pre-osteoblasts differentiation into mature osteoblasts and osteocytes, inducing changes in signaling pathways downstream of receptors, and ultimately remodeling and modifying the equilibrium between bone resorption and formation leading to increased bone resorption, morphological, and functional changes in bone maturation. EDCs can affect the IGF system, alkaline phosphatase, and osteocalcin gene expression. Findings are relative to both in vitro and in vivo studies. Studies have shown that prenatal exposure to EDCs leads to growth retardation, delayed ossification, and changes in bone length and size and in bone geometry with a lowering of bone mineral density and area-adjusted bone mineral content. Current knowledge on bone health, growth, mineral content, and development from molecular to clinical findings highlights how endocrine-disrupting chemicals can negatively affect these processes. Mechanisms, however, are not fully understood and need further investigation.

Prenatal Exposure to Multiple Endocrine-Disrupting Chemicals and Childhood BMI Trajectories in the INMA Cohort Study.

Prenatal exposure to endocrine-disrupting chemicals (EDCs) may disrupt normal fetal and postnatal growth. Studies have mainly focused on individual aspects of growth at specific time points using single chemical exposure models. However, humans are exposed to multiple EDCs simultaneously, and growth is a dynamic process. The objective of this study was to evaluate the associations between prenatal exposure to EDCs and children's body mass index (BMI) growth trajectories using single exposure and mixture modeling approaches. Using data from the INfancia y Medio Ambiente (INMA) Spanish birth cohort (), prenatal exposure to persistent chemicals [hexachlorobenzene (HCB), 4-4'-dichlorodiphenyldichloroethylene (DDE), polychlorinated biphenyls (PCB-138, -150, and -180), 4 perfluoroalkyl substances (PFAS)] and nonpersistent chemicals (8 phthalate metabolites, 7 phenols) was assessed using blood and spot urine concentrations. BMI growth trajectories were calculated from birth to 9 years of age using latent class growth analysis. Multinomial regression was used to assess associations for single exposures, and Bayesian weighted quantile sum (BWQS) regression was used to evaluate the EDC mixture's association with child growth trajectories. In single exposure models exposure to HCB, DDE, PCBs, and perfluorononanoic acid (PFNA) were associated with increased risk of belonging to a trajectory of lower birth size followed by accelerated BMI gain by 19%-32%, compared with a trajectory of average birth size and subsequent slower BMI gain [e.g., relative risk ratio (RRR) per doubling in DDE (95% CI: 1.05, 1.35); RRR for (95% CI: 1.05, 1.66)]. HCB and DDE exposure were also associated with higher probability of belonging to a trajectory of higher birth size and accelerated BMI gain. Results from the BWQS regression showed the mixture was positively associated with increased odds of belonging to a BMI trajectory of lower birth size and accelerated BMI gain (odds ratio per 1-quantile increase of the ; credible interval: 1.03, 2.61), with HCB, DDE, and PCBs contributing the most. This study provides evidence that prenatal EDC exposure, particularly persistent EDCs, may lead to BMI trajectories in childhood characterized by accelerated BMI gain. Given that accelerated growth is linked to a higher disease risk in later life, continued research is important. https://doi.org/10.1289/EHP11103.

Prenatal exposures to mixtures of endocrine disrupting chemicals and sex-specific associations with children’s BMI and overweight at 5.5 years of age in the SELMA study

BackgroundPrenatal exposure to mixtures of endocrine disrupting chemicals (EDC) has the potential to disrupt human metabolism. Prenatal periods are especially sensitive as many developmental processes are regulated by hormones. Prenatal exposure to EDCs has inconsistently been associated with children’s body mass index (BMI) and obesity. The objective of this study was to investigate if prenatal exposure to a mixture of EDCs was associated with children’s BMI and overweight (ISO-BMI ≥ 25) at 5.5 years of age, and if there were sex-specific effects. MethodsA total of 1,105 mother–child pairs with complete data on prenatal EDCs concentrations (e.g., phthalates, non-phthalate plasticizers, phenols, PAH, pesticides, PFAS, organochlorine pesticides, and PCBs), children’s measured height and weight, and selected covariates in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study were included in this analysis. The mixture effect of EDCs with children’s BMI and overweight was assessed using WQS regression with 100 repeated holdouts. A positively associated WQS index with higher BMI and odds of overweight was derived. Models with interaction term and stratified weights by sex was applied in order to evaluate sex-specific associations. ResultsA significant WQS*sex interaction term was identified and associations for boys and girls were in opposite directions. Higher prenatal exposure to a mixture of EDCs was associated with lower BMI (Mean β = -0.19, 95%CI: −0.40, 0.01) and lower odds of overweight (Mean OR = 0.72, 95%CI: 0.48, 1.04) among girls with borderline significance. However, the association among boys did not reach statistical significance. Among girls, the possible chemicals of concern were MEP, 2-OHPH, BPF, BPS, DPP and PFNA. ConclusionPrenatal exposure to a mixture of EDCs was associated with lower BMI and overweight among girls, and non-significant associations among boys. Chemicals of concern for girls included phthalates, non-phthalate plasticizers, bisphenols, PAHs, and PFAS.

Association of endocrine disrupting chemicals exposure with human chorionic gonadotropin concentrations in pregnancy

BackgroundHuman chorionic gonadotropin (hCG) is produced by the placenta and plays an essential role in the maintenance of pregnancy. Endocrine disrupting chemicals (EDCs) have the potential to interfere with functions related to the production and secretion of hCG; however associations between exposure to EDCs and hCG concentrations in humans remain to be elucidated. ObjectivesTo investigate the association of urinary, serum and plasma concentrations of EDCs during pregnancy with serum hCG concentrations. MethodsWe utilized data form the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study. We investigated the association of 26 EDCs measured in early pregnancy urine or blood with serum hCG concentrations using multi-variable adjusted linear regression models per EDC and Weighted Quantile Sum (WQS) regression with repeated holdout validation for the EDCs mixture. ResultsIn 2,039 included women, higher exposure to bisphenol A was associated with lower hCG (beta [95% CI]: −0.06 [−0.11 to −0.002]) while higher triclosan exposure was associated with a higher hCG (0.02 [0.003 to 0.04]). Higher exposure to several phthalates, including mono-ethyl and mono-butyl phthalates (MEP and MBP) as well as metabolites of di-2-ethylhexyl phthalate (DEHP) was associated with a lower hCG (beta [95% CI] for sum of DEHP metabolites: −0.13 [−0.19 to −0.07]). Likewise, higher exposure to several polychlorinated biphenyls (PCBs) was associated with a lower hCG. In the WQS regression, each quartile increase in the EDCs mixture was associated with −0.27 lower hCG (95% CI: −0.34 to −0.19). DiscussionHigher exposure to several EDCs during pregnancy was associated with a lower hCG; and despite the small effect sizes, still indicating that the exposure may negatively affect production or secretion of hCG by the placenta. Our results provide the impetus for future experimental studies to investigate the placenta as a target organ for adverse effects of EDCs.

Environmentally relevant doses of endocrine disrupting chemicals affect male fertility by interfering with sertoli cell glucose metabolism in mice

The growing global deterioration in several aspects of human health has been partly attributed to hazardous effects of endocrine-disrupting chemicals (EDCs) exposure. Therefore, experts and government regulatory agencies have consistently advocated for studies on the combined effects of EDCs that model human exposure to multiple environmental chemicals in real life. Here, we investigated how low concentrations of bisphenol A (BPA), and phthalates compounds affect the Sertoli cell glucose uptake/lactate production in the testis and male fertility. An EDC mixture containing a detected amount of each chemical compound in humans, called daily exposure (DE), and DE increased in magnitude by 25 (DE25), 250 (DE250), and 2500 (DE2500), and corn oil (control) were administered for six weeks to male mice. We found that DE activated estrogen receptor beta (Erβ) and glucose-regulated protein 78 (Grp 78) and disrupted the estradiol (E2) balance. In addition, DE25, DE250, and DE2500 doses of the EDC mixture via binding with Sertoli cells’ estrogen receptors (ERs) inhibited the glucose uptake and lactate production processes by downregulating glucose transporters (GLUTs) and glycolytic enzymes. As a result, endoplasmic reticulum stress (ERS), marked by unfolded protein response (UPR) activation, was induced. The accompanying upregulation of activating transcription factor 4 (ATF4), inositol requiring enzyme-1 (IRE1), C/EBP homologous protein (CHOP), and mitogen-activated protein kinase (MAPK) signaling promoted antioxidant depletion, testicular cell apoptosis, abnormal regulation of the blood−testis barrier, and decreased sperm count. Therefore, these findings suggest that human and wildlife exposure to multiple environmental chemicals can produce a wide range of reproductive health complications in male mammals.

O-091 The impact of endocrine disruptors on early pregnancy and clinical outcomes in IVF

Abstract The impact of endocrine disruptors on early pregnancy and clinical outcomes in IVF Moncef Benkhalifa (1,2,3), Debbie Montjean (2), Hafida Corsi-Cauet (3), Henri Copin (1,3), Véronique Bach (3), Pierre Miron (2), Rosalie Cabry (1,3) (1) Reproductive Medicine and Reproductive Genetics, University Hospital & School of Medicine. Picardie University Jules Verne. Amiens France (2) ART Centers. Laval and Brossard. Fertilys International Inc. Laval. Québec. Canada (3) PERITOX Laboratory. Picardie University Jules Verne. Amiens. France Since more than 40 years, there are annual increasing of studies, meta-analysis reporting and discussing the potential associations between endocrine disrupting chemicals (EDCs) and human fertility potential declining. Today it’s accepted that a substantial number of environmental and exposition factors affect the fertility and fecundity capacity of couples during the peri and post conception period. It’s accepted that most of EDCs interfere with or mimic steroid hormone action; predominantly by affecting estrogen, androgen and thyroid hormones signaling pathways and disturbing specific molecular process on relation with single or multiple biological functions. Some of EDCs can interact with the male and female reproductive system and lead to endocrine disruption in the testis and ovary. they exert their effects mainly via binding transcription factor receptors, EDCs can alter endocrine function through a variety of mechanisms. At fertility age EDCs may alter the expression and/or activity of enzymes required for synthesis and/or catabolism of testicular and ovarian sex steroids and the expression of hormone receptors and/or their ability to bind their and endogenous ligands. For example, in male, the literature reported a negative correlation between disrupted spermatogenesis and lifestyle factors (environmental-professional expositions) such as alcohol consumption, cigarette smoking, drug use, and obesity caused by high-energy diet. In female infertility diseases, the negative impact of chemicals ED has been studied in animals. Many disorders have been described, such as low ovarian weight, impaired folliculogenesis, a high aneuploidy rate and the acceleration of follicular atresia. Indeed, women exposed to some endocrine-disrupting pesticides (such as atrazine, lindane) have an elevated risk of long menstrual cycles or anovulation but the most serious consequence is POF and endometriosis pathophysiology’s. In our IVF experience in Picardie region (France), we observed that various pesticides with an endocrine-disrupting action are associated with poor oocyte quality (maturation and competency), embryonic defects and poor IVF outcomes, and some pesticide compounds are linked to specific causes of female infertility, such as premature ovarian insufficiency, polycystic ovarian syndrome, and endometriosis. It was reported that EDCs can reduce embryo implantation chances and increase miscarriage, placenta and post-natal abnormalities. for endometrium receptivity and implantation failure EDCs can play by modifying keys elements of the immune response relevant to pregnancy, and disrupt immune tolerance required for robust placentation, optimal fetal development and be a as contributing risk factors in recurrent miscarriage, preeclampsia, preterm birth and related pathologic gestation Environmental insults, including endocrine disrupting chemicals during critical periods of fetal development, can alter DNA methylation patterns, leading to inappropriate developmental gene expression and disease risks. Similar to environmental factors, endocrine-disrupting chemicals can influence gene expression without modifying the DNA sequence. It is commonly accepted that the transgenerational inheritance of parentally acquired traits is conveyed by epigenetic alterations risks also known as “epimutations”. In Conclusion, the negative impact of exposure to various endocrine-disrupting is becoming now a worldwide public health. Indeed, the community should be informed about the fertility decline, low ongoing pregnancy rates, and elevated risk of miscarriage associated with exposure to high doses of pesticides for example. We must keep in mind that humans are exposed to EDCs mixtures composed of hundreds of chemicals every day and not a single chemical in isolation.

Mixed and single effects of endocrine disrupting chemicals in follicular fluid on likelihood of diminished ovarian reserve: A case-control study

Endocrine-disrupting chemicals (EDCs) are a group of the most widely spread pollutants. Their impacts on reproductive health have become public concerns. Diminished ovarian reserve (DOR) is a disorder of ovarian function. Associations between EDC and DOR have been inconsistent. Very little research investigated the joint effects of multiple EDCs. Here, we performed a case-control study among 64 DOR women and 86 controls. Twenty-one EDC chemicals were assessed in follicular fluid, including parabens, phenols, phthalates and poly-fluoroalkyl substances. Both mixed and single effects of EDCs on DOR were evaluated and validated with a Bayesian kernel machine and logistic regressions. We found that the likelihood of DOR significantly increased with rising levels of the 21-EDC mixture, with an odds ratio (OR) and 95% confidence interval (CI) of 2.12 (1.17–3.83) for the 75th percentile compared to its median level. The overall effect was higher than effects of each subgroup. BP4, MECPP, and PFHxA were driving the association to the mixture, and their single effects were validated, with individual ORs of 8.25 (95%CI:3.45–12.21), 1.92 (95%CI:1.02–4.09), and 1.84 (95%CI:1.08–3.86), respectively. In conclusion, we provided new pollutant markers for DOR and emphasized the importance of the effects of EDC mixtures on female reproductive health.

Exposure to endocrine-disrupting chemicals and implications for neurodevelopment.

Human brain development is a complex multistep process that is partly coordinated by the endocrine system. Any interference with the endocrine system might affect this process and result in deleterious outcomes. Endocrine-disrupting chemicals (EDCs) represent a large group of exogenous chemicals with the capacity of interfering with endocrine functions. In different population-based settings, associations between exposure to EDCs, particularly in prenatal life, and adverse neurodevelopmental outcomes have been demonstrated. These findings are strengthened by numerous experimental studies. Although mechanisms underlying these associations are not entirely delineated, disruption of thyroid hormone and, to a lesser extent, sex hormone signalling have been shown to be involved. Humans are constantly exposed to mixtures of EDCs, and further research combining epidemiological and experimental settings is required to improve our understanding of the link between real-life exposures to these chemicals and their impact on neurodevelopment.

Removal of endocrine-disrupting chemical mixtures in water using chlorination and photolysis

Abstract Micropollutants have been continuously detected in freshwater. In parallel, the potential adverse effects of human exposure to endocrine-disrupting chemicals (EDCs) through drinking water have been gaining the attention of researchers and health authorities. Given this fact, this study aimed to evaluate the effectiveness of chlorination and photolysis to remove the estrogenic activity caused by mixtures of EDCs in water: estrone (E1: 100 ng L−1), 17β-estradiol (E2: 100 ng L−1), ethinylestradiol (EE2: 50 ng L−1), and nonylphenol (NP: 1,000 ng L−1) under operating conditions applicable for water treatment plants. The tests were performed using freshwater spiked with the following mixtures: E1 + E2, E1 + E2 + EE2, E1 + E2 + NP, and E1 + E2 + EE2 + NP). Removal efficiencies of up to 99.7% were achieved at a chlorine dose of 2.75 mg L–1 and 30 min of contact time. In photolysis, estrogenic activity removal was higher than 99.9% at a UV dose of 186 mJ cm–2. Results indicated that both chlorination and photolysis can be efficient to remove the estrogenic activity caused by the tested EDC mixtures in water. Furthermore, experiments suggested that EDC mixtures can be efficiently removed at feasible water disinfection operating conditions.