Parabens are a family of alkyl esters of 4-hydroxybenzoic acid. The most commonly used include methylparaben, ethylparaben, propylparaben, and butylparaben. These compounds have been reported to disrupt the endocrine system and are believed to affect the central nervous, immune, and reproductive systems, as well as lipid homeostasis, glucose levels, and thyroid function. Given these effects, parabens pose potential health risks, including their possible link to conditions like diabesity - a term describing the dual condition of type 2 diabetes mellitus and obesity. This review explores current literature on how parabens may influence key mechanisms in diabesity, such as gluconeogenesis, glycogenolysis, adipogenesis, insulin resistance, and inflammation. Understanding their role in these metabolic pathways is critical for assessing their contribution to the diabesity epidemic and guiding future research for minimizing their harmful health impacts.

Previous studies have reported the thyroid disruptive effects of prenatal phthalate exposure; however, evidence on the impact of prenatal phthalate alternative exposure on neonatal thyroid function is still limited. We aimed to investigate the associations between prenatal exposure to phthalates and phthalate alternatives (individually and as a mixture) and neonatal thyroid function, based on longitudinal data from the Wuhan Healthy Baby Cohort Study. We measured concentrations of phthalate and phthalate alternative metabolites (mPAEs) in urine samples, provided by 1202 mothers at three trimesters, and neonatal thyroid stimulating hormone (TSH) levels in heel-prick blood samples. The results suggested higher levels of some mPAEs, particularly monomethyl phthalate (MMP) and mono-2-ethyl-5-Carboxypentyl terephthalate (MECPTP), were associated with increased neonatal TSH. Interquartile range (IQR) increases of mPAEs were associated with an increase in TSH ranging from 8.21 % to 13.5 %, and the associations were more likely to occur in girls. Quantiles g-computation models revealed that joint exposure to phthalates was significantly associated with increased TSH in three trimesters, MEOHP and MMP were the most predominant contributors to the positive associations. The research results imply that prenatal phthalate exposure may interfere with thyroid hormone homeostasis, which warrants further replication.

Isothiazolinone biocides have been widely used as disinfectants during the COVID-19 pandemic. However, their effects on gonadal steroidogenesis remain unclear. This study investigated the endocrine-disrupting potential of isothiazolinone biocides, focusing on their inhibition of gonadal 3β-hydroxysteroid dehydrogenases (3β-HSDs). Enzymatic assays, molecular docking, and 3D-QSAR analyses evaluated the impact of seven isothiazolinones on human KGN cell 3β-HSD2 (h3β-HSD2) and rat testicular 3β-HSD1 (r3β-HSD1). Dichlorooctylisothiazolinone, butylbenzo[d]isothiazol-3(2 H)-one, octylisothiazolinone, and benzisothiazolinone inhibited h3β-HSD2 with IC50 values of 4.02, 15.35, 12.12, and 30.55 μM, respectively. These compounds also inhibited r3β-HSD1 with IC50 values of 1.67, 16.51, 13.25, and 29.28 μM, respectively. Whereas, methylchloroisothiazolinone selectively inhibited r3β-HSD1 with IC50 value of 40.11 μM. The compounds acted as mixed/noncompetitive inhibitors, targeting the NAD+ binding pocket. Inhibitory potency correlated with compound hydrophobicity, heavy atom count, and molecular weight. A 3D-QSAR pharmacophore model achieved high predictive accuracy (R2 = 0.98) for h3β-HSD2 inhibition. These biocides suppressed progesterone production in human KGN granulosa tumor cells. The binding free energies were ranged from -6.52 to -7.19 kcal/mol for h3β-HSD2 and -6.0 to -7.04 kcal/mol for r3β-HSD1. The results underscore the endocrine-disrupting capabilities of isothiazolinones via inhibition of critical steroidogenic enzymes, offering insights into their structure-activity relationships and potential side effects.

Endocrine-disrupting chemicals (EDCs) can interfere with endocrine function and lead to neurological damage. Neurofilament light chain (NfL) is a protein released into the blood after neuroaxonal damage, and it has become a dependable biomarker for neurological conditions. The study aimed to investigate the associations between single or combined EDCs exposure and serum NfL levels in adults.

The 1372 participants included in the study were from the 2013-2014 National Health and Nutrition Examination Survey. Due to the difference in types of EDCs, participants were divided into two populations. Multiple linear regression models were used to assess the association between 32 EDCs and NfL. The least absolute shrinkage and selection operator regression model was used for EDCs selection and the weighted quantile sum (WQS) regression was used for examining the association of EDCs mixture with NfL and identify the predominant exposure.

Levels of urinary bisphenol S, mono(2-ethylhexyl) phthalate, dibutyl phosphate, glyphosate, and 3,5,6-trichloropyridinol were positively associated with serum NfL levels, while benzophenone-3, methylparaben, and propylparaben showed negative associations. In the WQS regression model, the changes of NfL were 0.154 (95 % CI: 0.014-0.294) and 0.164 (95 % CI: 0.033-0.296) for each quartile increase in WQS index of EDCs mixture in the two populations, respectively. Analysis of the subgroup with gender stratification suggested that the association between EDCs mixture and NfL was only significant in men. The positive mixture β was 0.219 (95 % CI: 0.056-0.380) and 0.257 (95 % CI: 0.082-0.433) in the two population, respectively.

The study suggested a potential association between single or combined exposure to EDCs and NfL levels. High-level EDCs exposure might be associated with more severe neurological damage, particularly in men.

Tris(chloropropyl) phosphate (TCPP) is a member of organophosphate flame retardants used commonly as a replacement for polybrominated diphenyl ethers in consumer and commercial products. Flame retardants have been shown to modulate immune function in vivo and in vitro and there is evidence that at least some related compounds such as organophosphate pesticides can cause developmental immunotoxicity. Developmental immunotoxicology studies were conducted by administering 0, 2500, 5000, or 10,000 ppm TCPP in feed to pregnant Hsd:Sprague Dawley SD rats from gestation day 6 through weaning on postnatal day 28. Feed exposure to TCPP was continued in the F1 offspring until terminal euthanasia at ∼16 to 21 weeks of age when assessments for developmental immunotoxicity were conducted. Innate, humoral, and cell-mediated immune function were assessed in the F1 adults. The antibody-forming cells (AFCs) response to sheep red blood cells was reduced in male and female F1 rats in the 10,000 ppm treatment group but coincided with reduced bodyweights. The AFC response was also significantly reduced in male rats exposed to 5000 ppm where only moderate effects on bodyweights occurred. TCPP exposure affected baseline T-cell proliferation without stimulation; however, the relevance of this change for immunotoxicity risk is unknown. TCPP exposure did not affect cytotoxic T-lymphocyte activity. Only minor and inconsistent treatment-related effects on hematology, innate NK cell function, and immune cell population distributions in the spleen were observed. Taken together, these data indicate that TCPP has the potential to impact humoral immune responses following developmental exposure.

Endocrine-disrupting chemicals (EDCs) are ubiquitous emerging environmental contaminants. However, the comprehensive impact of EDCs on soil ecosystems, particularly on the model organism Eisenia fetida, remains inadequately understood due to disparate experimental and assessment methods. A meta-analysis was conducted to analyze the effects of EDCs on earthworm functional traits, including survival, behavior, growth, reproduction, and cellular responses. The analysis revealed that EDCs significantly impaired earthworm survival (-17.5%, p < 0.05), behavior (-62.2%, p < 0.001), growth (-11.5%, p < 0.001), and reproduction (-36.7%, p < 0.001). EDCs induced substantial oxidative stress, evidenced by a 36.5% (p < 0.001) increase in reactive oxygen species (ROS) production and elevated oxidative damage. The antioxidant defense system showed compensatory activation, with enhanced superoxide dismutase (10.0%) and catalase (8.90%) activities and glutathione levels (23.3%) (p < 0.001). The present study found chemical-specific toxicity patterns with heavy metals causing the most severe effects on behavior and reproduction. Toxicity profiles varied with exposure concentration and duration, revealing complex dose-response and temporal relationships. These findings provide crucial insights for the ecological risk assessment of EDCs and establish a foundation for developing targeted mitigation strategies. Furthermore, the findings highlight the importance of taking multiple endpoints into account when evaluating the toxicity of EDCs and suggest possible directions for future research.

Iodine is a critical trace element in the human body. It is primarily obtained through dietary sources such as dairy products, seafood, fish, eggs and certain vegetables. Iodine plays an essential role in various bodily functions, most notably in producing the thyroid hormones, triiodothyronine and thyroxine. Additionally, it influences the immune, cardiovascular, reproductive and gastrointestinal systems. Historically, iodine deficiency has been a significant global health issue; however, over the past decade, there has been a rise in iodine excess. This surge has been primarily attributed to inadequate monitoring and over-iodization of salt. Despite the well-documented consequences of iodine deficiency, the ramifications of excessive iodine intake remain underexplored. In view of rising global infertility rates, excess iodine has been linked to significant reproductive health effects. These include decreased sperm count, motility and morphology in males, as well as adverse pregnancy outcomes in females, such as maternal thyroid dysfunction and congenital hypothyroidism. This mini-review aims to collate and analyze current literature pertaining to the effects of iodine excess on reproductive health and shed light on its increasing incidence worldwide. Further research on the biological and clinical effects of iodine excess is required to derive a better understanding of this issue. Given the rising prevalence of iodine excess, it is crucial to raise awareness and implement proactive measures to prevent it from escalating into a major public health crisis in the future.

Endocrine disrupting-chemicals (EDCs) are chemical compounds found in the environment that can have adverse impacts on human health. Among these agents are tributyltin (TBT) and bisphenol S (BPS). TBT is used in anti-fouling paints, and its indiscriminate use has health repercussions. BPS is found in plastic products and marketed as a safe alternative to bisphenol A (BPA). Little is known about the effects resulting from interactions between different EDCs on the organisms. The aim of this study was to analyze changes induced by exposure to these compounds in hypothalamic-pituitary-gonadal (HPG) axis and uterus. We divided four groups: Control, TBT 100 ng kg-1.day-1, BPS 50 μg kg-1.day-1, and the group simultaneously exposed to TBT and BPS. Rats were gavaged for 15 days and euthanized in the estrus phase. All EDCs groups showed uterus with cellular hyperplasia, glandular degeneration, increased epithelial thickness, and vacuolization. In the ovaries, there was an increase in atretic follicles in all EDCs groups. In the hypothalamus, the group exposed to the mixture showed an increase in the GnRH gene. In the blood, all EDCs groups had reduced levels of FSH and LH. Additionally, the BPS and mixture groups exhibited reduced levels of prolactin. Therefore, we suggest that exposure to these agents may contribute to damage to the female reproductive system, and that doses considered safe by regulatory agencies need to be reassessed.

Endocrine-disrupting chemicals (EDCs) are exogenous compounds that interact with the estrogen receptor (ER), thereby disrupting estrogen-mediated signaling. In a previous study, we employed a bioluminescence resonance energy transfer (BRET) system to assess ER dimerization for detecting EDCs. To further determine whether the BRET assay could be used independently to identify EDCs, we investigated ER-EDC interactions before and after dimerization. Results from isothermal titration calorimetry (ITC) and dynamic light scattering (DLS) revealed that ER dimerization can be mediated by EDCs. Consequently, the BRET assay proved effective in detecting dimerization and clarifying its relevance to EDC-induced signaling disruption. Additionally, to examine EDC-induced transcriptional changes, we performed chromatin immunoprecipitation sequencing (ChIP-seq), followed by gene ontology (GO) analysis. These analyses demonstrated that EDCs affect various signaling pathways, including those involved in antibody-dependent cytotoxicity, bone morphogenetic protein (BMP) signaling in cardiac induction, and hepatocyte growth factor receptor signaling. Overall, this study elucidates the molecular mechanisms by which EDCs influence ER dimerization and signaling. These findings highlight the utility of the BRET-based assay for EDC detection and contribute to a deeper understanding of the systemic effects of EDCs on endocrine disruption.

Organophosphate esters (OPEs) are synthetic chemicals used in consumer products as flame retardants and plasticizers. OPEs are potential endocrine disruptors, but little is known regarding gestational OPE exposure and maternal sex steroid hormones in human pregnancy.

Understanding Pregnancy Signals and Infant Development (UPSIDE) cohort participants (n=265) provided biospecimens and completed questionnaires in each trimester. In second trimester samples, we measured urinary OPE metabolite concentrations using HPLC-MS/MS. In second and third trimester serum samples, we measured sex steroids (total testosterone [TT], free testosterone, estrone [E1], estradiol [E2], and estriol [E3]) using LC-MS/MS. We fitted linear regression and linear mixed models examining each log-transformed, specific gravity-adjusted OPE metabolite in relation to sex steroid concentrations, adjusting for covariates. Three OPEs with >70% detection were considered continuously; six less prevalent metabolites were dichotomized (above vs below lower limit of detection). Secondary models were fit for male and female fetuses, separately. Results are shown as % difference in hormone levels.

Percent detection of OPEs ranged from 26% to 100%. Diphenyl phosphate (DPHP) had the highest concentration (median 0.9 ng/mL). Across trimesters 2 and 3, a log-unit increase in dibutyl phosphate/di-isobutyl phosphate (DBUP/DIBP) was associated with lower TT (%Δ = -6.6, 95%CI: 11.5, -1.5), E1 (%Δ = -5.6, 95%CI: 10.8, -0.1), and E2 (%Δ = -5.3, 95%CI: 8.2, -2.3). Compared to those with non-detectable levels, participants with detectable bis(methylphenyl) phosphate (BMPP) had lower E3 (%Δ = -45.9, 95%CI: 67.9, -8.9) and participants with detectable bis(2-chloroethyl) phosphate (BCETP) had lower E2 (%Δ = -1.4, 95%CI: 2.4, -0.4). Numerous associations were observed in trimesters 2 and 3, individually. We observed several differences by fetal sex that varied in magnitude and direction.

OPEs may act as endocrine disruptors by altering maternal sex steroid hormones during pregnancy, with some differences by fetal sex. Further research is needed to understand implications for maternal and child health.

Exposure to air pollution during pregnancy that disrupts thyroid function can lead to adverse health outcomes in mother and child. We evaluated the overall effect and critical exposure window of residential ambient air pollution exposures on thyroid function in the MADRES pregnancy cohort. We also investigated whether these associations varied by iodine deficiency status and neighborhood deprivation. Early pregnancy (6-20 weeks) serum thyroid stimulating hormone (TSH) and free thyroxine (FT4) were measured for 217 mothers. Daily residential ambient air pollution exposures (PM2.5, PM10, NO2 and O3 8hr max) were estimated using inverse-distance squared spatial interpolation from regulatory monitors. We used linear regression to assess effects of single ambient air pollutants on thyroid function, including exploration of effect modification by iodine deficiency and neighborhood deprivation (Area Deprivation Index and Gini Index of income inequality, dichotomized at the median). Distributed lag models (DLM) were used to assess critical windows of exposure for ambient air pollutants from 12 weeks preconception to first trimester. We found that one SD increase in PM2.5 (2.4 μg/m3) and PM10 (5.8 μg/m3) were associated with 18.9 % (95 % CI: 2.7, 37.8 %) and 16.8 % (95 % CI: 0.7, 35.6 %) higher TSH levels, respectively, with significant windows of susceptibility in the first trimester (GW 5-8 or 6-8). These associations were also modified by neighborhood deprivation, and iodine status. Our findings indicate that relatively low levels of PM exposures in early pregnancy are associated with increased TSH levels particularly among women with replete iodine levels and women living in neighborhoods with greater deprivation.

This study investigated the consequences of perinatal exposure to Aroclor 1221 (A1221), a weakly estrogenic polychlorinated biphenyl (PCB) mixture and known endocrine-disrupting chemical (EDC), in female rats. Previous work has shown behavioral and physiological effects of A1221, and the current study extended this work to comprehensive transcriptomic profiling of two hypothalamic regions involved in the control of reproduction: the arcuate nucleus (ARC) and anteroventral periventricular nucleus (AVPV). Female Sprague-Dawley rats were fed a cookie treated with a small volume of A1221 (1 mg/kg) or vehicle (3% DMSO in sesame oil) during pregnancy from gestational days 8-18 and after birth from postnatal (P) days 1-21, exposing the offspring via placental and lactational transfer. In female offspring, developmental, physiological, and hormonal effects of A1221 were relatively modest. However, because prior work has implicated this exposure in neurobehavioral disruptions, we sought to determine whether developmental programming of the brain transcriptome could underlie these latter phenotypes. We used 3' targeted RNA sequencing in the hypothalamus (arcuate nucleus, anteroventral periventricular nucleus) of experimental females at P8, 30, and 60 and identified significant alterations in gene expression and gene ontology (GO) terms in an age- and tissue-specific manner. Most notably, terms related to synaptic signaling, neurotransmitter regulation, immune response, and cellular structure were identified. Changes in pathways associated with synaptic functions and cellular metabolism were further identified, indicating that A1221 exposure can impact neurodevelopmental and neuroendocrine processes at a molecular level, even in the absence of overt developmental changes. These findings of molecular reprogramming may explain the behavioral effects of A1221 and highlight novel molecular targets and pathways that warrant further investigation to understand the effects of EDCs on the developing brain.

There is growing evidence that endocrine disruptive chemicals have deleterious effects on sexual and reproductive function. To examine subjective sexual functions in human females and their relationship to postnatal phthalate exposure and perinatal androgenization, a Sexuality Score (SS) was established from a first-stage survey questionnaire of subjective sexual function filled out by female university students (n = 68; average age 25.23 ± 5.17 years; rural 25.51 ± 6.74 vs. urban 25.85 ± 1.43 years). Seventeen phthalate metabolites in urine samples were analyzed by high-performance liquid chromatography (HPLC) and tandem mass spectrometry (MS/MS). Females were also assessed for the 2D:4D digit ratio as an index of perinatal androgenization. The mean age of menarche was 12.82 ± 1.35 years (rural 12.59 ± 1.39 vs. urban 13.18 ± 1.27; p = 0.01). The mean age at first sexual intercourse was 14.88 ± 6.89 years (rural 14.62 ± 7.20 vs. urban 15.24 ± 6.55), and as the age of first sexual intercourse increases, the SS score tends to increase as well, albeit moderately (r = 0.25, p = 0.037). Mono-iso-butyl phthalate, mono(2-ethyl-5-carboxypentyl) phthalate, mono(hydroxy-n-butyl) phthalate, mono(2-ethyl-5-oxohexyl) phthalate (p ≤ 0.05) and mono(2-carboxymethylhexyl) phthalate (p ≤ 0.01) were negatively associated with SS. A compounding butterfly effect of prenatal exposure to androgens was observed with disruptive effects of mono(2-ethyl-5-oxohexyl) phthalate and mono(2-ethyl-5-carboxypentyl) phthalate on sexual function. Exposure to phthalates in adult females may lead to disruption of subjective sexual function, especially concerning sexual desire and sexual satisfaction, and perinatal androgenization could augment these effects.

Existing literature indicates that phthalates can be toxic to the ovaries, negatively affecting female reproduction and potentially influencing outcomes in assisted reproductive technology (ART). However, data on associations between urinary and/or follicular fluid phthalate concentrations and ART outcomes in South American women are scarce. Therefore, in this prospective study, we recruited 93 women (n = 119 cycles) undergoing ART at a fertility clinic in Brazil. They provided urine and follicular fluid (FF) samples, from which we measured the concentrations of the 15 phthalate metabolites more frequently found in Brazilian populations. We documented both laboratorial and clinical outcomes, estimating associations using negative binomial regression. Our findings revealed that specific oocyte and embryo development parameters were associated with urinary concentrations of phthalate metabolite. Particularly, number of follicles, maturation, as well as blastulation were negatively associated with Mono-benzyl phthalate (MBzP). Similarly, urinary mono-ethyl phthalate (MEP) was associated with lower rates of maturation, good quality and blastulation. However, some parameters positively associated with mono-(carboxyisooctyl) phthalate (MCiOP), including maturation, good quality, and blastulation. We also observed certain associations between embryo development and FF concentrations of phthalate metabolite, although the magnitude and direction of these associations differed among various metabolites. Overall, our results suggest that urinary and FF concentrations of phthalate metabolite may be linked to altered outcomes in ART cycles. However, further studies are needed to clarify the extent of this impact. Our results support previous literature and is the first to evaluate urinary and FF phthalate metabolites concentrations in South American women undergoing infertility treatment.

The large-scale industrial production characteristic of the last century led to an increase in man-made compounds and mobilization of natural compounds, many of which can accumulate in the environment and organisms due to their bioaccumulation and biomagnification properties. The endocrine system is especially vulnerable to these compounds that are known as endocrine disruptor chemicals (EDCs). Thyroid hormones (THs) are essential for normal development and growth, besides being the main regulators of basal metabolic rate. Thus, compounds able to affect THs synthesis, transport, and action could produce important deleterious effects, impacting the development of metabolic and endocrine diseases. Herein, we will review the main effects of EDCs on the thyroid axis, with special emphasis on the widely used substances bisphenol A (BPA), employed in the synthesis of polycarbonate plastics and epoxy resins; tributyltin (TBT), an organotin chemical substance widely used in several agro-industrial applications; and lead (Pb), a ubiquitous environmental and occupational polluting heavy metal. Exposure to these EDCs occurs mainly from the ingestion of contaminated food and beverages. Furthermore, there are few epidemiological studies evaluating human risk, and experimental studies employ different exposure models, making it difficult to integrate results. However, even low doses of these EDCs warn of thyrotoxicity. Since THs homeostasis is essential for health and humans are increasingly being exposed to EDCs, it is important to clarify which substances might act as thyroid hormone system disrupting chemicals and how they act in order to try to overcome their deleterious effects and limit the exposure to these compounds.

Environmental pollutants significantly impact liver disease development, progression, and outcomes. This review examines the complex relationship between environmental exposures and liver pathology, from malignant conditions like hepatocellular carcinoma to steatotic and cholestatic liver diseases. Key environmental factors include air pollutants, volatile organic compounds, persistent organic pollutants, heavy metals, and per- and polyfluoroalkyl substances. These compounds can act through multiple mechanisms, including endocrine disruption, metabolic perturbation, oxidative stress, and direct hepatotoxicity. The impact of these exposures is often modified by factors such as sex, diet, and genetic predisposition. Recent research has revealed that even low-level exposures to certain chemicals can significantly affect liver health, particularly when combined with other risk factors. The emergence of exposomics as a research tool promises to enhance our understanding of how environmental factors influence liver disease. Importantly, exposure effects can vary by demographic and socioeconomic factors, highlighting environmental justice concerns. Implementation of this knowledge in clinical practice requires new diagnostic approaches, healthcare system adaptations, and increased awareness among medical professionals. In conclusion, this review provides a comprehensive examination of current evidence linking environmental exposures to liver disease and discusses implications for clinical practice and public health policy.

Epidemiological data shows that the prevalence of multiple sclerosis (MS) and the female-to-male sex ratio among MS patients are increasing over time. Endocrine disrupting chemicals (EDCs) are ubiquitous and increasingly recognized for effects on estrogen signaling. This study aimed to determine whether there was an association between EDC levels and disease severity in newly diagnosed, female MS patients.

This exploratory observational cohort study enrolled female patients, ages 18-60, via written informed consent from the Brigham MS Center. Enrollment criteria included diagnosis with MS within the past 5 years and completion of a questionnaire about potential EDC exposures. Exclusion criteria were intravenous steroids in the past 30 days. Collection processes and materials were designed to avoid EDC contamination. Urine samples were analyzed by NSF International (Ann Arbor, Michigan). Primary outcome measures were MRI parameters and clinical disease activity, including multivariable analysis adjusting for MS treatment types. Spearman correlation test was used for analysis and between group comparisons were conducted with one-way ANOVA.

68 patients with MS were enrolled. In the phthalates, mEOHP was negatively correlated with T2 lesion volume over time (R value = -0.522, p-value = 0.002, Bonferroni adjusted p = 0.03). For the phenols, triclocarban was negatively associated with cheese consumption (R value = -0.402, p = 0.001, Bonferroni adjusted p = 0.012) There was no association between EDCs and disease activity or demographic factors, nor significant correlation with exposure to household plastics.

This exploratory study identified a negative correlation between triclocarban and cheese consumption. Longitudinally, phthalate metabolite mEOHP was negatively correlated with T2 lesion volume over time. Exposure to EDCs may affect the early disease course in MS, and expansion of research efforts is warranted.

This study aimed to investigate the association between estimated dietary intake of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) and human sperm quality. This study cross-sectionally assessed the associations between estimated dietary intake of PCDD/Fs and sperm quality parameters in 200 participants aged 18-40 years from the Led-Fertyl study. Linear regression models, accounting for potential confounding variables, were employed to evaluate the relationships. To estimate the PCDD/Fs exposure, food frequency questionnaires and the latest data on PCDD/Fs concentrations in food, primarily from Spanish sources, were used. Our findings indicate that, in comparison to participants in the lowest tertile, those in the highest tertile (T3) of PCDD/Fs dietary intake exhibited significantly elevated body mass index, increased consumption of meat, fish and eggs, and decreased consumption of nuts. Furthermore, individuals in T3 demonstrated a higher percentage of sperm head abnormalities (4.65 % [0.10; 9.24]; p-trend= 0.037) and a corresponding increase per 1-SD increment in energy-adjusted total PCDD/Fs dietary intake (1.84 % [0.38; 3.68]). No significant associations for other sperm parameters were found. Minimal research exists on PCDD/F dietary exposure and human sperm quality. This study shows significant direct association between higher PCDD/Fs intake and the percentage of sperm head abnormalities which potentially may compromise human reproductive health.

The adrenal glands play crucial roles in regulating metabolism, blood pressure, immune system function, and response to stress through the secretion of hormones. Despite their critical functions, the adrenal glands are often overlooked in studies on the effects of potential toxicants. Research across human, animal, and in vitro studies has identified more than 60 compounds that can induce adrenocortical toxicity. These compounds, known as endocrine-disrupting chemicals (EDCs), are natural or synthetic substances that interfere with the endocrine system. This review aims to provide an overview of the effects of 4 major families of EDCs-flame retardants, bisphenols, phthalates, and microplastics-on the function of the adrenal glands. The PubMed database was searched for studies reporting the effects of the chemicals in these 4 families on the adrenal glands. There is clear evidence that the morphology and function of the adrenal gland are affected, particularly through disrupting the steroidogenic pathway. Additionally, some EDCs have been shown to exert transgenerational effects, raising further concerns about their long-term effect. However, most EDCs have not been thoroughly evaluated for their effects on the function of the adrenal glands, especially in human studies. Thus, developing regulatory testing guideline to include the adrenal glands in the screening of EDCs is urgently needed.

Endocrine disruptive chemicals (EDCs) are considered as the potential attributes for the increasing trend in obesity and metabolic syndrome (MS) through disruption of sex hormones, particularly in women. We evaluated the association of understudied EDC compounds with total testosterone (TT), sex hormone-binding globulin (SHBG), obesity, and MS. A population-based cross-sectional study was conducted using the National Health and Nutrition Examination Survey datasets collected during the years 2013-2016. Women of age ≥15 years with urinary measurements of nonpersistent EDCs, including bisphenol, triclosan, triclocarban, dichlorophenol, and paraben compounds were included in this study. Data were analyzed using the modified Poisson models to estimate the adjusted relative risk (RR) and 95% confidence interval (CI). The associations were also validated by considering TT and SHBG concentrations as the outcomes. The study included 1974 women with 11% high TT, 10.5% low SHBG, 40% obesity, and 46.2% MS. A medium to high exposure to bisphenol-A (RR = 1.64; 95% CI: 1.14, 2.35, p = 0.009), bisphenol-F (RR = 1.83; 95% CI: 1.35, 2.49, p < 0.001), bisphenol-S (RR = 1.83; 95% CI: 1.35, 2.49, p = 0.041) and 2, 4- dichlorophenol (RR = 1.61; 95% CI: 1.06, 2.45, p = 0.026) were associated with low SHBG but not with high TT. In addition, high exposure to triclosan was also inversely associated with SHBG concentrations (regression coefficient = -0.09; 95% CI: -0.15, -0.02, p = 0.013). However, these EDCs were found to be associated with SHBG, obesity, and MS according to menopausal status. High exposure to certain nonpersistent EDCs was associated with low SHBG, obesity, and MS according to menopausal status.

Breast cancer is a major public health problem, and distant metastases are the main cause of morbidity and mortality. Chlorpyrifos is an organophosphate that promotes Epithelial-Mesenchymal Transition-like phenotype in breast cancer cell lines and modulates the Breast Cancer Stem Cells activating two key processes related to the metastatic cascade. Here, we investigated whether Chlorpyrifos may induce distant metastases in an in vivo triple negative tumor model. Also, we studied the expression of Breast Cancer Stem Cell and Epithelial-Mesenchymal Transition activation-markers in Triple Negative Breast Cancer mice tumors and human cells. We demonstrate that Chlorpyrifos modulates stem cell plasticity as a function of growth conditions in monolayer or three-dimensional culture. Furthermore, Chlorpyrifos decreased the doubling period, increased tumor volume, stimulated the infiltration of adjacent muscle fibers and induced lung and lymphatic node metastases in mice. Finally, Chlorpyrifos modulated the expression of Epithelial-Mesenchymal Transition and Breast Cancer Stem Cell markers in mice exposed to the pesticide. All our findings confirm that Chlorpyrifos promotes breast cancer progression, enhances stemness and Epithelial-Mesenchymal Transition marker expression and generates lung metastases in an in vivo model induced in mice.

Breast milk (BM) is the main nutrition source for infants that plays a key role on growth and development. Human milk composition includes endogenous and exogenous substances, including endocrine disrupting chemicals (EDCs). EDCs are man-made environmental chemicals present in everyday environment and food that can disrupt the programming of endocrine signalling pathways during development, resulting in adverse effects that may not be apparent until much later in life. The presence of single and/or mixtures of EDCs in BM has been shown to be associated with impairment of reproductive, metabolic, immunologic system and neurobehavioral developmental outcomes. This systematic review discusses the current knowledge about the presence of EDCs in BM, and their potential effects on infant outcomes during the first six years of life. Following PRISMA guidelines, we made a systematic evaluation of the literature on the effects of single and mixtures EDC on (i) mental and psychomotor development; (ii) socio-communicative and behavioral development. Negative association between EDC exposure and developmental areas considered emerged highlighting: (i) BM as a potential key matrix for the monitoring of EDC exposure (ii) the short- and long-term negative effect on infant neuro-behavioral outcomes, and (iii) the importance of public health efforts to reduce maternal and infant EDC exposure. However, heterogeneous results found emphasizes the need to further longitudinal studies to consider factors that can lower EDC exposure or exert a protective role on infant neurodevelopment, and to better understand the mechanism behind the EDCs and its effects on infant development.

Studies have shown that mercury (Hg) exposure during pregnancy is associated with adverse birth outcomes (ABO) in infants, but the association between the two has not been systematically summarized. Therefore, we conducted a systematic review and meta-analysis of existing observational studies on the association between maternal Hg exposure (MHE) during pregnancy and ABO in infants to evaluate the association between them. We comprehensively searched all relevant literature published in three electronic databases (Web of Science, PubMed, Embase) from 2004 to June 2024. According to the heterogeneity, fixed effect model (I2 ≤ 50 %) or random effect model (I2 > 50 %) was used to pool the associated effect values. The results showed a positive association between MHE and low birth weight (LBW) (OR = 1.079, 95 % CI: 1.032-1.128) and no statistically significant association between and preterm birth (PTB) (OR = 1.044, 95 % CI: 0.956-1.140) and small-for-gestational-age (SGA) (OR = 1.006, 95 % CI: 0.983-1.030). In addition, each 10-fold increase in MHE during pregnancy was associated with abnormal Birth Anthropometrics. These findings suggest that MHE is a risk factor for LBW and is associated with abnormal anthropometric measurements at birth. However, there is insufficient evidence for Hg exposure and SGA, PTB. Further population-based studies are warranted to investigate these associations.

Estrogens are a group of endocrine disruptors that are recognized as a threat to the world's ecosystems and are easily transported through aquatic systems from mainly anthropogenic sources. To illustrate this growing problem, we have compiled a global overview of measured concentrations of natural and synthetic estrogens restricted to freshwater systems (lakes, rivers, and lagoons) and marine coastal and open ocean environments, focusing on estrone (E1), 17β-estradiol (E2), estriol (E3), and 17α-ethinylestradiol (EE2). We found that the cumulative risk quotient is high at 65% of 400 sampled sites, highlighting that estrogen pollution is a major environmental concern. Our investigation revealed that almost no information is available on the concentration levels of E1, E2, E3, and EE2 for the open ocean areas. However, their occurrence in all systems, including open seas, suggests that estrogens are not completely degraded during transport to and within the environment and may be more persistent than previously thought.

Endocrine-disrupting chemicals (EDCs) are compounds, either natural or man-made, that interfere with the normal functioning of the endocrine system. There is increasing evidence that exposure to EDCs can have profound adverse effects on reproduction, metabolic disorders, neurological alterations, and increased risk of hormone-dependent cancer. Stem cells (SCs) are integral to these pathological processes, and it is therefore crucial to understand how EDCs may influence SC functionality. This review examines the literature on different types of EDCs and their effects on various types of SCs, including embryonic, adult, and cancer SCs. Possible molecular mechanisms through which EDCs may influence the phenotype of SCs are also evaluated. Finally, the possible implications of these effects on human health are discussed. The available literature demonstrates that EDCs can influence the biology of SCs in a variety of ways, including by altering hormonal pathways, DNA damage, epigenetic changes, reactive oxygen species production and alterations in the gene expression patterns. These disruptions may lead to a variety of cell fates and diseases later in adulthood including increased risk of endocrine disorders, obesity, infertility, reproductive abnormalities, and cancer. Therefore, the review emphasizes the importance of raising broader awareness regarding the intricate impact of EDCs on human health.

Hepatic metabolism is an important process for evaluate the potential activity and toxicity of endocrine disrupting chemicals (EDCs) metabolites. Organization for Economic Co-operation and Development (OECD) has advocated the development of in vitro assays that mimic in vivo hepatic metabolism to eventually replace classical animal tests. In response to this need, we established a 3D mouse liver organoid (mLO) platform that mimics the animal model and is distinct from existing models. We evaluated the effects the activity of EDC metabolites generated through mLOs based on human cell-based reporter gene assays in addition to existing models. This study emphasizes the importance of hepatic ex-vivo and suggests the need a new metabolic model through a 3D mLOs platform. These results indicate that mLOs provides a novel biological method to screen for potential endocrine-disrupting activities of EDC metabolites.

The use of Bisphenol A (BPA) has been widely restricted due to its adverse health effects. Bisphenol Z (BPZ) is used as an alternative to BPA, and humans are widely exposed to BPZ through various routes. Recent studies have shown that BPZ exposure adversely affects mouse oocyte meiotic maturation. This study investigates the impact of BPZ exposure on early mouse embryonic development alongside an exploration of the underlying mechanisms. The findings reveal that exposure to BPZ leads to a reduction in early embryo quality and hinders developmental progression. RNA sequencing analysis has identified 593 differentially expressed genes as a result of BPZ exposure, highlighting considerable changes in early embryonic gene expression. Mechanistically, BPZ exposure inhibits the activation of the zygotic genome and impedes maternal mRNA degradation, thereby interfering with maternal-to-zygotic transition (MZT). Further analysis indicates compromised mitochondrial function, as evidenced by abnormal distribution, diminished membrane potential, and lower ATP levels. Consequently, BPZ-exposed embryos exhibit elevated levels of reactive oxygen species, superoxide anions, and oxidative DNA damage. Moreover, BPZ exposure is associated with an increase in γ-H2A.X expression. Additionally, BPZ exposure alters the expression levels of histone modifications, including H3K27me2, H3K27me3, H3K9me3, and H3K27ac, in early embryos. Collectively, BPZ exposure significantly impairs early embryo quality by disrupting mitochondrial function, inducing oxidative stress and DNA damage, altering histone modifications, and inhibiting MZT, ultimately resulting in hindered blastocyst formation. These findings underscore the profound adverse effects of BPZ on early embryonic development, indicating the need for caution when considering it as a safe alternative to BPA.

Endocrine disrupting chemicals (EDCs) can cross the placenta and thereby expose the fetus, which may lead to developmental consequences. It is still unclear which chemicals are of concern regarding neurodevelopment and specifically behaviour, when being exposed to a mixture.

The objective is to determine associations between prenatal exposure to EDCs and behavioural difficulties. Furthermore, we investigated sex-specific associations and determined chemicals of concern in significant regressions.

Associations between prenatal exposure to EDCs (both as single compounds and their mixtures) and behavioural outcomes using the Strengths and Difficulties Questionnaire (SDQ) were estimated in 607 mother-child pairs in the Swedish Environmental Longitudinal, Mother and Child, Asthma and Allergy (SELMA) study. Levels for chemical compounds were measured in either urine or serum (median of 10 weeks of gestation). Associations were estimated for the total SDQ score (quasipoisson regression) and a 90th percentile cut-off (logistic regression). Exposure for EDC mixtures (phenols, phthalates, PFAS and persistent chlorinated) was studied using weighted quantile sum (WQS) regression with deciles and with and without repeated holdout validation techniques. The models were adjusted for selected covariates.

The odds for behavioural difficulties increased in girls with higher chemical exposures (OR 1.77, 95% CI 1.67, 1.87) using the full sample and borderline for the validation set (OR 1.31, 95% CI 0.93, 1.85) with 94/100 positive betas in the 100 repeated holdout validations. Chemicals of concern for girls are mostly short-lived chemicals and more specifically plasticizers. No pattern of significant associations was detected for boys.

There is an indication of increased behavioural difficulties for girls in the SELMA population with higher exposure to mixtures of EDCs. Using the repeated holdout validation techniques, the inference is more stable, reproducible and generalisable. Prenatal exposure to mixtures of environmental chemicals should be considered when assessing the safety of chemicals.

Growing evidence points towards a "mixture effect" where different environmental chemicals might act jointly where individual compounds may be below a level of concern, but the combination may have an effect on human health. We are constantly exposed to a complicated mixture pattern that is individual for every person as this mixture depends on personal choices of lifestyle, diet and housing to name a few. Our study suggests that prenatal exposure to EDCs might adversely affect the behaviour of children and especially girls. Hence, risk assessment needs to improve and sex-specific mechanisms should be included in assessments.

Infertility is recognized as a multifaceted condition affecting approximately 15% of couples globally, influenced by various factors including genetic predisposition and environmental exposures. Among these environmental factors, bisphenol A (BPA) emerges as a prominent Endocrine-disrupting chemical (EDCs) widely distributed, leading to chronic human exposure in daily life. As regulations on BPA became more stringent, alternative substances such as bisphenol S (BPS) and bisphenol F (BPF) have emerged. Animal studies have demonstrated a dose-dependent decline in fertility and embryotoxicity following chronic exposure to BPA. However, literature data on human studies are limited and heterogeneous. Additionally, even less is known about the relationship between exposure to the BPA analogues (BPS and BPF) and sperm quality. Therefore, the present study aimed to examine the association between urinary concentrations of BPA, BPF, and BPS and semen quality parameters among 195 adult Spanish men from the Led-Fertyl study cohort using multiple linear regression models adjusted by potential confounding variables. Our results revealed an inverse association between log-transformed creatinine-adjusted concentration (ng/mg) of BPA and BPF levels and the percentage of sperm vitality (β: 3.56 %; 95%CI: 6.48 to -0.63 and β: 4.14 %; 95%CI: 6.97 to -1.31; respectively). Furthermore, participants in the highest quartile of BPA and BPF urinary concentration exhibited lower sperm vitality compared to those in the lowest quartile (β: 6.90 %; 95%CI: 11.60 to -2.15 and β: 9.68 %; 95%CI: 14.43 to -4.94; respectively). These results supply epidemiological evidence establishing a relationship between bisphenols urine exposure and sperm quality, suggesting that a re-evaluation of the overall safety of BPA alternatives is warranted.

The use of New Approach Methodologies (NAMs), such as Quantitative Structure-Activity Relationship (QSAR) models, is highly recommended by international regulations to speed up hazard and risk assessment of Endocrine Disruptors, which are known to be linked to a wide spectrum of severe diseases on humans and wildlife. A very sensitive target for these chemicals is the thyroid hormone system, which plays a key role in regulating metabolic and cognitive functions. Several chemicals have been demonstrated to compete with the thyroid hormone thyroxine (T4) for binding to human thyroid hormone distributor protein transthyretin (hTTR). In this work, we generated three new datasets composed by T4-hTTR competing potencies of more than 200 heterogeneous chemicals measured by three different in vitro assays. These datasets were used for the development of new regression QSAR models. The best models were thoroughly validated by internal and external validation procedures. The mechanistic interpretation of the selected molecular descriptors provided information on structural features which are relevant to characterise hTTR binders, such as the presence of hydroxylated and halogenated aromatic rings. PCA analysis was used to rank the studied chemicals according to their increasing T4-hTTR competing potency. Hydroxylated and halogenated bicyclic aromatic compounds are ranked as the strongest hTTR binders. The new QSARs are useful to screen potential Thyroid Hormone System-Disrupting Chemicals (THSDCs), and to support the identification of sustainable alternatives to hazardous chemicals.

Over the last decades, the human species has seen an increase in the incidence of pathologies linked to the genitourinary tract. Observations in animals have allowed us to link these increases, at least in part, to changes in the environment and, in particular, to an increasing presence of endocrine disruptors. These can be physical agents, such as light or heat; natural products, such as phytoestrogens; or chemicals produced by humans. Endocrine disruptors may interfere with the signaling pathways mediated by the endocrine system, particularly those linked to sex hormones. These factors and their general effects are presented before focusing on the male and female genitourinary tracts by describing their anatomy, development, and pathologies, including bladder and prostate cancer.

Obesity is a major risk factor for noncommunicable diseases and is associated with a reduced life expectancy of up to 20 years, as well as with other consequences such as unemployment and increased economic burden for society. It is a multifactorial disease, and physiopathology of obesity involves dysregulated calorie utilization and energy balance, disrupted homeostasis of appetite and satiety, lifestyle factors including sedentary lifestyle, lower socioeconomic status, genetic predisposition, epigenetics, and environmental factors. Some endocrine-disrupting chemicals (EDCs) have been proposed as "obesogens" that stimulate adipogenesis leading to obesity. In this review, definition of obesogens, their adverse effects, underlying mechanisms, and metabolic implications will be updated and discussed.

Disruption of lipid homeostasis by EDCs involves multiple mechanisms including increase in the number and size of adipocytes, disruption of endocrine-regulated adiposity and metabolism, alteration of hypothalamic regulation of appetite, satiety, food preference and energy balance, and modification of insulin sensitivity in the liver, skeletal muscle, pancreas, gastrointestinal system, and the brain. At a cellular level, obesogens can exert their endocrine disruptive effects by interfering with peroxisome proliferator-activated receptors and steroid receptors. Human exposure to chemical obesogens mainly occurs by ingestion and, to some extent, by inhalation and dermal uptake, usually in an unconscious manner. Persistent pollutants are lipophilic features; thus, they bioaccumulate in adipose tissue.

Although there are an increasing number of reports studying the effects of obesogens, their mechanisms of action remain to be elucidated. In addition, epidemiological studies are needed in order to evaluate human exposure to obesogens.

Endogenous oestrogens regulate essential functions to include menstrual cycles, energy balance, adipose tissue distribution, pancreatic β-cell function, insulin sensitivity and lipid homeostasis. Oestrogens are a family of hormones which include oestradiol (E2), oestrone (E1) and oestriol (E3). Oestrogens function by binding and activating oestrogen receptors (ERs). Phytoestrogens are plant-derived compounds which exhibit oestrogenic-like activity and can bind to ERs. Phytoestrogens exert potential oestrogenic-like benefits; however, their effects are context-dependent and require cautious consideration regarding generalised health benefits. Xenoestrogens are synthetic compounds which have been determined to disrupt endocrine function through binding to ERs. Xenoestrogens enter the body through various routes and given their chemical structure they can accumulate, posing long-term health risks. Xenoestrogens interfere with endogenous oestrogens and their functions contributing to conditions like cancer, infertility, and metabolic disorders. Understanding the interplay between endogenous and exogenous oestrogens is critical in order to determine their potential health consequences and requires further investigation. This manuscript provides a summary of the role endogenous oestrogens have in regulating metabolic functions. Additionally, we discuss the impact phytoestrogens and synthetic xenoestrogens have on biological systems across various life stages. We highlight their mechanisms of action, potential benefits, risks and discuss the need for further research to bridge gaps in understanding and mitigate exposure-related health risks.

The mammary gland is responsive to endogenous hormones and environmental chemicals that are estrogen receptor (ER) agonists. The mouse mammary gland offers the opportunity to dissect the most sensitive windows of exposure. 17α-ethinyl estradiol (EE2) is a pharmaceutical ER agonist that often serves as a positive control for estrogen-active chemicals. Here, adult female mice were exposed to EE2 starting either at pregnancy day 7, or on lactational day 1, and exposures continued until the litters were weaned. The pups were therefore exposed during gestation + the juvenile period, or during the juvenile period alone. The morphology of the mammary gland was evaluated in both male and female offspring at two life stages: weaning (postnatal day [PND]21) and at puberty (PND32). Other hormone-sensitive outcomes evaluated included body weight, anogenital index, frequency of open vagina, and weight of the uterus. We found age- and sex-dependent effects of EE2 on these estrogen-responsive endpoints including the morphology of the mammary gland. Importantly, EE2 altered mammary gland morphology even when exposures were limited to the juvenile period. However, the number of endpoints that were affected in animals from the EE2-Juvenile-Only period were fewer, and typically of a lower magnitude, compared to those observed in the EE2-Gest-Juvenile group. Understanding the effects of environmental estrogen exposures during the juvenile period is critical because humans are exposed to estrogenic pollutants throughout life, including in early childhood.

Increasing evidence supports an association of endocrine-disrupting chemical (EDC) exposures with adverse biological effects in humans and wildlife. Recent studies reveal that health consequences of environmental exposures may persist or emerge across generations. This creates a dual conundrum: that we are exposed to contemporary environmental chemicals overlaid upon the inheritance of our ancestors' exposure profiles. Even when legacy EDCs are phased out, they may remain relevant due to persistence in the environment together with intergenerational inheritance of their adverse biological effects. Thus, we all possess a body burden of legacy contaminants, and we are also increasingly exposed to new generations of EDCs.

We assessed the effects of direct and ancestral exposures to EDCs across six generations on anxiety-like behaviors in male rats using our "two hits, three generations apart" multigenerational EDC exposure experimental model. We investigated two classes of EDCs with distinct hormonal actions and historical use-the weakly estrogenic polychlorinated biphenyl (PCB) mixture Aroclor 1221 (A1221) and the anti-androgenic fungicide vinclozolin (VIN)-in both the maternal and paternal line. We also determined if a hormonal mechanism drives these effects across generations.

Rats were gestationally exposed to A1221, VIN, or vehicle [dimethyl sulfoxide (DMSO)] in the F1 generation. Three generations later, the F4 generation was given the same or a different exposure. Anxiety-like behavior was measured in the open field test, light:dark box, and elevated plus maze across generations. Serum was collected at the end of the experiment, and concentrations of estradiol and corticosterone were analyzed.

Although direct exposure did not affect behavior in F1 males, ancestral exposure to VIN decreased anxiety-like behavior in the F3 paternal line compared to vehicle. In the F4 paternal line, ancestral A1221 followed by direct exposure to VIN increased anxiety-like behavior compared to controls. In the F6 maternal line, relative to vehicle, the double ancestral hits of A1221/VIN decreased anxiety-like behavior. Serum hormones weakly predicted behavioral changes in the F4 paternal line and were modestly affected in the F4 and F6 maternal lines.

Our data suggest that anxiety-like behavioral phenotypes emerge transgenerationally in male rats in response to EDC exposure and that multiple hits of either the same or a different EDC can increase the impact in a lineage-specific manner. https://doi.org/10.1289/EHP15684.

This study, using Mendelian randomization, reveals a causal link between nitrogen oxides and PM2.5 exposure and reduced total-body bone mineral density, highlighting a potential risk factor for osteoporosis. The findings emphasize the importance of targeted interventions in populations exposed to higher air pollution.

With the aging of the population, the prevalence of osteoporosis is escalating. Observational studies suggest that air pollution might diminish bone mineral density (BMD), contributing to elevating the likelihood of developing osteoporosis.

Employing a two-sample Mendelian randomization (MR) analysis, our study aimed to explore the potential causal effect of air pollution on total-body BMD. We utilized extensive publicly available data from genome-wide association studies (GWAS) in this research. Inverse variance weighting was selected for the primary effect estimation, complemented by additional approaches such as the weighted median, MR-Egger, simple mode, and weighted mode. Sensitivity analyses were then conducted to evaluate heterogeneity, pleiotropy, and the presence of outliers.

In the MR analysis, our findings revealed causal associations between nitrogen oxides (β =  - 0.55, 95% CI - 0.90 to - 0.21, P = 0.002) and particulate matter (PM) 2.5 (β =  - 0.33, 95% CI - 0.59 to - 0.08, P = 0.010) and a reduction in total-body BMD. No significant associations were detected between PM2.5-10, PM10, nitrogen dioxide, and total-body BMD (P > 0.05). Rigorous sensitivity analyses verified the stability of these significant results.

Our study illustrates that exposure to nitrogen oxides and PM2.5 may lead to a decrease in total-body BMD, increasing the risk of osteoporosis. This evidence holds crucial implications for policymakers and healthcare providers, as it can provide targeted interventions for the prevention of osteoporosis.

Female reproductive aging often affects women's emotional, physical, and physiological well-being. Ovarian aging is characterized by fluctuations in reproductive hormones and determines the age at which menopause occurs. Understanding potentially modifiable factors that influence this process is essential for addressing health disparities, improving quality of life, and informing relevant public health strategies. This review synthesizes in vivo, in vitro, and epidemiological findings about the effects of endocrine-disrupting chemicals (EDCs), specifically heavy metals and perfluoroalkyl and polyfluoroalkyl substances (PFAS) on female reproductive aging. Most in vivo and in vitro studies have demonstrated that heavy metals alter ovarian morphology, folliculogenesis, and steroidogenesis. Evidence regarding the effects of PFAS is limited and inconsistent. Epidemiological studies have consistently shown that heavy metals are associated with a higher risk of diminished ovarian reserve (indicated by decreased anti-Müllerian hormone) and earlier menopause, with limited findings regarding reproductive hormone changes. PFAS exposure has been associated with decreased estradiol and earlier menopause but not significantly with ovarian reserve. Gaps in the literature require more comprehensive epidemiological research on the effects of EDCs on female reproductive aging, including ovarian reserve, age at menopause, and vasomotor symptoms, to inform future interventions to reduce hazardous exposures and improve women's health.

This review examines the longstanding debate of nature and intrauterine environmental challenges that shapes human development and behavior, with a special focus on the influence of maternal prenatal gut microbes. Recent research has revealed the critical role of the gut microbiome in human neurodevelopment, and evidence suggest that maternal microbiota can impact fetal gene and microenvironment composition, as well as immunophysiology and neurochemical responses. Furthermore, intrauterine neuroepigenetic regulation may be influenced by maternal microbiota, capable of having long-lasting effects on offspring behavior and cognition. By examining the complex relationship between maternal prenatal gut microbes and human development, this review highlights the importance of early-life environmental factors in shaping neurodevelopment and cognition.

Zearalenone (ZEN), a secondary metabolite of Fusarium fungi, is one of the most common mycotoxins in global food supplies such as cereal grains and processed food. ZEN and its metabolites are commonly referred to as mycoestrogens, due to their ability to directly bind nuclear estrogen receptors α (ER-α) and β (ER-β). Zeranol, a synthetic mycoestrogen, is administered to U.S. cattle as a growth promoter. Despite widespread human exposure and ample evidence of adverse reproductive impacts in vitro and in vivo, there has been little epidemiological research on the health impacts of ZEN exposure during pregnancy. The objective of our study was to examine associations between ZEN and gestational weight gain (GWG).

Urine samples were collected in each trimester from pregnant participants in the UPSIDE cohort (n = 286, Rochester, NY, USA). High performance liquid chromatography and high-resolution tandem mass spectrometry were used to quantify concentrations of ZEN as well as ∑mycoestrogens (composite sum of ZEN metabolites; ng/ml). Maternal weights at clinical visits were abstracted from medical records. We fitted longitudinal models of specific-gravity adjusted, log-transformed ZEN and ∑mycoestrogens in relation to total GWG (kilograms) and GWG rate (kilograms/week). We additionally examined risk of excessive GWG (in relation to Institute of Medicine guidelines) and considered effect modification by fetal sex.

ZEN and ∑mycoestrogens were detected in > 93% and > 95% of samples, respectively. Mycoestrogen concentrations were positively associated with total GWG (ZEN β:0.50 kg; 95%CI: 0.13, 0.87) and GWG rate (ZEN β:0.20 kg/week; 95%CI: 0.01, 0.03). Associations tended to be stronger among participants carrying male (versus female) fetuses and results were robust to adjustment for diet.

Mycoestrogen exposure during pregnancy may contribute to greater GWG. Future research is needed to understand potential influences on downstream maternal and offspring health.

Nowadays, two of the endocrine disrupting compounds (EDCs) in the group of alkylphenols (APs), nonylphenol (4-NP) and octylphenol (4-t-OP), have attracted great scientific and regulatory attention mainly due to concerns about their aquatic toxicity and endocrine disrupting activity. This paper investigated the occurrence, distribution behavior, fate, and removal of 4-NP and 4-t-OP in liquid and solid phases of three full-scale wastewater treatment plants (WWTPs) with different treatment technologies comparatively. In this context, (i) advanced biological WWTP, (ii) wastewater stabilization pond (WSP), and (iii) constructed wetland (CW) were utilized. In all three investigated WWTPs, the concentrations of 4-NP (219.9-19,354.4 ng/L) in raw wastewater were higher than those of 4-t-OP (13.9-2822.4 ng/L). Within the scope of annual average removal efficiencies, 4-NP was treated highly in advanced biological WWTP (93.5 %), while it was almost not treated in WSP (3.1 %) and treated with negative removal (<0 %) in CW. While 4-t-OP was treated at a similar removal rate (93.5 %) to 4-NP in advanced biological WWTP, it was treated moderately in WSP (52.5 %) and very poorly in CW (12.4 %). It has been determined that the most important removal mechanism of both 4-NP and 4-t-OP in WWTPs is biodegradation, followed by sorption onto sewage sludge. According to the mass balance performed in advanced biological WWTP, the biodegradation rates for 4-NP and 4-t-OP were found to be 70.4 % and 86.6 %, respectively, while the sorption onto sewage sludge were determined to be 23.3 % and 6.8 %. One of the critical findings obtained within the scope of the study is that while the concentrations of both metabolites, especially 4-NP, in wastewater and sewage sludge, decreased considerably under aerobic conditions, on the contrary, their concentrations increased significantly under anaerobic conditions. Both compounds were detected at higher concentrations in primary sludge compared to secondary sludge in advanced biological WWTP, while in WSP, they were determined at higher concentrations in anaerobic stabilization pond sludge compared to facultative stabilization pond sludge. Besides, it was also determined that the sorption behavior of these alkylphenols is much more dominant than desorption.