Alternative phthalates (APs) have been developed due to the reported adverse effects of conventional phthalates (CPs). However, whether APs are nontoxic and can replace CPs remains controversial due to their endocrine-disrupting (ED) effects. Herein, to investigate the ED potential of diethyl-hexyl-cyclohexane (DEHCH), a newly developed non-phthalate-structured AP, we employed in silico (molecular docking simulation), in vitro (cell-based assays for estrogen and androgen receptors), and in vivo (zebrafish embryo model) methods. We also compared the results with two CPs (di(2-ethylhexyl) phthalate [DEHP] and diisononyl phthalate [DINP]) and two previously proposed non-phthalate-structured APs (1,2-cyclohexane dicarboxylic acid diisononyl ester [DINCH] and di-2-ethylhexyl terephthalate [DEHTP]). DEHCH did not exhibit the highest binding affinity for any of the five receptors such as estrogen, androgen, glucocorticoid receptors, and thyroid receptor alpha and beta. None of the tested phthalates exhibited agonistic or antagonistic effects on estrogen and androgen receptors. In zebrafish larvae, DEHCH did not affect the expression of the nine endocrine-related genes and neurobehaviors, which correlates well with the lack of changes in the endogenous concentrations of the five neurosteroids. In contrast, DINCH, DEHP, and DEHTP induced hyperactivity, and except for DEHCH, four phthalates significantly upregulated at least one gene. In addition, DINCH significantly increased the expression of cortisol and DEHP increased progesterone, allopregnanolone, and cortisol. These findings demonstrate that DEHCH is safer than CPs and the previously proposed APs in terms of ED effects, including neuronal system dysregulation.

Exposure to per- and polyfluoroalkyl substances (PFAS) has been linked to adverse effects on women's fertility. However, information on the transfer of PFAS from blood to follicular fluid (FF) and individual characteristics influencing this process remains limited. We estimated the blood-to-FF transfer efficiencies (BFTEs) of 32 PFAS in samples from 576 women undergoing in vitro fertilization, and identified structural and physico-chemical predictors of BFTEs. The median BFTEs of PFAS ranged from 0.364 to 0.914. Carbon chain length, isomeric structure, functional group and physico-chemical properties including octanol-water partition coefficient (logKow), membrane-water partition coefficient (logKmw), dissociation constant (Kd) and protein-water partition coefficient (logKpw) were determinants of BFTEs. For example, the BFTEs of perfluorooctane sulfonate (PFOS) isomers ranked as follows: n-PFOS (0.753) > iso-PFOS (0.710) > 3 + 4 +5m-PFOS (0.612) > 1m-PFOS (0.587). One unit increase in carbon chain length, logKow, logKmw, Kd and logKpw was associated with BFTE differences of -0.05 (95 % CI: -0.06, -0.04), -0.16 (95 %CI: -0.19, -0.13), -0.07 (95 % CI: -0.10, -0.04), -0.13 (95 % CI: -0.19, -0.08), and 0.22 (95 % CI: 0.14, 0.29), respectively. However, individual characteristics were not associated with BFTEs. This study suggests that molecular structure and physico-chemical properties are critical factors in assessing reproductive health risk related to PFAS.

The role of endocrine disrupting chemicals (EDCs) in the development of metabolic syndrome has gained increasing recognition in recent years. The underlying mechanisms are largely unresolved. Disruption of corticosteroid action and hypothalamic-pituitary-adrenal (HPA) axis are considered possible mechanisms.

To summarise epidemiological studies investigating an association between EDC concentration and altered levels of corticosteroids and the adrenocorticotropic hormone (ACTH).

Following the PRISMA guidelines, we searched PubMed and the Cochrane Library for epidemiological studies published from database inception until April 1st, 2024. Various groups of EDCs were evaluated with the prerequisite of direct measurement of the chemical, a metabolite, or biomarker.

We identified 2094 articles. After removing duplicates and screening, 27 studies were included. Studies focused predominantly on glucocorticoids (n = 26) compared to mineralocorticoids (n = 5) and ACTH (n = 2). The most studied EDCs were pesticides (n = 9) and phthalates (n = 8). Significant associations between the concentrations of specific EDCs and hormone levels were found in all but three studies. Only one study described an association between EDCs, and hormone concentration and metabolic features.

There is clear evidence for the impact of specific EDCs on plasma corticosteroid concentrations in different age groups worldwide, however, results varied according to EDC class, study population and study methodology. Further research combining EDC and hormone concentrations, and clinical features, complemented by experimental investigations to study cell mechanisms, is needed to gain holistic knowledge of EDCs' influence on glucocorticoid- and mineralocorticoid-related disorders.

IVF as a clinical method to surmount infertility has existed since the 1970s, and yet fertilization, embryo development, pregnancy, and live birth rates remain unacceptably low. Although a multitude of factors may contribute to stagnated success despite substantial advances in basic and applied IVF sciences, gamete quality is inarguably integral to IVF success rates. In this review, the authors will explore the role of environmental toxicology in impairing in vivo fertility and gamete quality prior to starting IVF that will influence downstream IVF success. In vivo contaminants of interest that may affect gamete potential in the context of IVF include heavy metals, per- and polyfluoroalkyl substances (PFAS), persistent organic pollutants (POPs), and airborne contaminants. By evaluating the current literature on reproductive toxicology and how toxic exposures may influence IVF, this review aims to provide a comprehensive reference of potential toxicological exposures for clinicians, to use in vitro and animal data to supplement correlative human studies with potential causative mechanisms, and to strengthen the case for patient assessment of toxicological risk.

Breast cancer (BC) is one of the most common types of cancer and is caused by the complex interplay of genetic and environmental factors, such as an unhealthy lifestyle, family history of illness, reproductive factors, and ageing. However, increasing evidence has revealed that manufactured organic pollutants such as bisphenols are closely related to BC. Bisphenols exposure can promote the progression of BC through multiple complicated and variable molecular mechanisms. Reanalysis of existing data on this topic may reveal molecular markers with clinical value. In this study, we identified four key genes [keratin 14 (KRT14), keratin 5 (KRT5), acyl-CoA synthetase long chain family member 1 (ACSL1) and matrix metallopeptidase 1 (MMP1)] related to both bisphenols exposure and BC by employing the Comparative Toxicogenomics Database (CTD) and The Cancer Genome Atlas Cervical Cancer (TCGA-CESC) dataset; notably, KRT14 expression exhibited the most significant difference between tumour and normal tissues. Further analysis of the functions and biological processes associated with KRT14 and related regulatory molecules revealed that bisphenols exposure induces BC-promoting characteristics and aggressive behaviour-related signaling pathways, such as the steroid biosynthesis, Forkhead box (FOXO) and prolactin signaling pathways. To confirm the expression and biological effects of KRT14, we conducted relevant experiments. In vitro studies revealed that bisphenols such as bisphenol A (BPA) exposure significantly affected the proliferation, migration, and invasion of MCF-7 cells by inhibiting KRT14 expression. Similarly, we also observed a decrease in KRT14 expression in BPA induced abnormal breast tissue in mice. In summary, our study revealed potential genes and pathways associated with bisphenols exposure in BC.

Some medical professional organizations have advocated for including the menstrual cycle as a vital sign in adolescence, but not in adulthood. However, documenting menstrual cycle patterns is not routine clinical or research practice. Vital signs are used to predict health outcomes, indicate needed treatment, and monitor a clinical course. They can help identify pathologies, affirm wellness, and are responsive to exposures. Here we review the scientific evidence showing how the menstrual cycle meets these criteria and should therefore be treated as a vital sign. Using key words and controlled vocabulary terms, we carried out multiple literature searches, prioritizing the inclusion of systematic reviews, meta-analyses, and clinical practice guidelines. This review describes how the menstrual cycle is a health indicator, can cyclically impact health conditions, and its associations with long-term post-menopausal health outcomes. We review exposures influencing the menstrual cycle, evidence underlying its use to optimize wellness, and available tools for documenting cycles. Supplementary materials include patient handouts on menstrual cycle tracking, and an index of related clinical practice guidelines and reviews by subject. The menstrual cycle is a vital sign from menarche through menopause, an underutilized but powerful tool for understanding gynecological and general health.

Synthetic chemicals like triethyl citrate (TEC) are widely used in food packaging, pharmaceuticals, and cosmetics. Despite being considered safe, there are concerns about TEC's potential neurotoxic effects. In this study, we used network toxicology and molecular docking to examine TEC's impact on the nervous system. We identified 229 targets related to neurotoxicity and found that TEC may affect key processes such as cell death, inflammation, and neuronal health. Molecular docking showed strong interactions between TEC and proteins like MAPK3, SRC, CASP3, TNF, and BCL2, suggesting a risk of neural damage and the need for further research to assess TEC's safety.

This review aims to provide a comprehensive overview to understand the role of pollution in the development of noncommunicable diseases (NCDs), with a focus on metabolic diseases.

In the context of NCDs, the incidence of metabolic diseases such as obesity and diabetes are increasing at an alarming rate. In addition to the well-known role of the so-called "obesogenic" environment, characterized by unhealthy diet and physical inactivity, great attention has been paid in recent years to the effects of pollution. Indeed, progressive urbanization has been associated with increased exposure to pollutants. The harmful effects of some pollutants on the endocrine system have been known for decades, but data on the metabolic impact of pollution are rather recent. Pollution in its various forms promotes a systemic inflammatory state, insulin resistance, and oxidative stress, which appear to be closely associated with increased risk of NCD, particularly obesity and diabetes.

In conclusion, urbanization has so far had a predominantly negative impact on collective health, but a better understanding of the mechanisms linking pollution to metabolic health is crucial to implement preventive strategies, including careful urban planning to improve community health, understood not only as the absence of disease but also as psychological and social well-being, overcoming the risks associated with urbanization.

About 8-10 % of all people of reproductive age are unable to conceive children. In recent years, an increased number of consultations for fertility treatments has been observed with a continuing positive trend. It is known that infertility itself and assisted reproductive technologies (ARTs) are frequently associated with recurrent miscarriages, pregnancy complications or psychosocial problems. In parallel, metabolic and vascular diseases and obesity are becoming a growing issue, even among the younger population, and are affecting fertility and pregnancy outcomes of mother and child. Possible interactions between these conditions and the underlying mechanisms are not well understood hitherto. Furthermore, reproductive outcomes are increasingly challenged by the potential effects of environmental pollution on key reproductive processes, including oocyte maturation and atresia, sperm quality, implantation as well as their role in recurrent miscarriages. The Leipzig reproductive health (LE-REP) project is aimed at investigating the interplay between ARTs and the aforementioned reproductive challenges, including different aspects of fertility problems, early and late pregnancy as well as long-term effects on mothers and their children born via fertility treatment. This multidisciplinary initiative is expected to provide a deep understanding of underlying mechanisms, providing a framework for future preventive strategies improving reproductive health. Finally, LE-REP aims to establish a high-level university fertility center of excellence, combining advanced clinical care, cutting-edge research and education to train future reproductive medicine specialists.

Human health depends on planetary health, and yet healthcare provision can have unintended consequences for the health of the planet. Emissions from the healthcare sector include greenhouse gases, air pollution and plastic pollution, alongside chemical contamination. Chemical pollution resulting in endocrine disruption has been associated with plastics, which are a source of concerning additives such as phthalates, bisphenols, perfluoroalkyl and polyfluoroalkyl substances, and flame retardants (all routinely found in healthcare products). Many endocrine-disrupting chemicals are persistent and ubiquitous in the environment (including water and food sources), with potential secondary harms for human health, including disrupting reproductive, metabolic and thyroid function. Here we review evidence-based strategies for mitigating environmental effects of healthcare delivery. We focus on what endocrinologists can do, including reducing demand for healthcare services through better preventative health, focusing on high-value care and improving sustainability of medical equipment and pharmaceuticals through adopting circular economy principles (including reduce, reuse and, as a last resort, recycle). The specific issue of endocrine-disrupting chemicals might be mitigated through responsible disposal and processing, alongside advocating for the use of alternative materials and replacing additive chemicals with those that have lower toxicity profiles, as well as tighter regulations. We must work to urgently transition to sustainable models of care provision, minimizing negative effects on human and planetary health.

Endocrine-disrupting chemicals (EDCs), such as bisphenol A (BPA), bisphenol S (BPS), phthalates, and micro- and nanoplastics, present substantial environmental and health hazards because of their potential to disrupt hormonal systems. Micro- and nanoplastics can release EDCs that disrupt reproductive and developmental processes, potentially affecting future generations. BPA, a common plasticizer and resin component, mimics estrogen and disrupts thyroid hormone metabolism, contributing to obesity, diabetes, and cardiovascular issues. BPS, a BPA substitute, exhibits similar endocrine-disrupting properties and persists longer in the environment. Phthalates, which are widely used as plasticizers, are associated with reproductive issues, metabolic conditions, and developmental issues in children. Combined exposure to multiple EDCs can amplify health risks, underscoring the need for further research on the synergistic impacts of these chemicals. This review underscores the urgent need for effective regulatory measures and further investigations into the health impacts of EDCs to mitigate their harmful impacts on the health of humans and the environment.

Endocrine disrupting chemicals (EDCs) are ubiquitous in the environment and have been shown to interfere with the endocrine system, leading to adverse effects on reproductive health. In females, EDC exposure has been linked to menstrual irregularities, infertility, and pregnancy complications. Epigenetic regulation, which involves modifications to DNA and histones that do not alter the underlying genetic code, plays a crucial role in female reproduction. EDCs have been shown to disrupt epigenetic mechanisms, leading to changes in gene expression that can have long-term effects on reproductive outcomes. Several EDCs, including bisphenol A (BPA) and phthalates, dioxins, and polychlorinated biphenyls (PCBs), have been shown to alter DNA methylation patterns and histone modifications in female reproductive tissues. These changes can lead to altered expression of genes involved in ovarian function, implantation, and placental development. Here, we integrate epidemiological and experimental evidence from the last 20 years to profile the types of diseases that EDCs trigger in the female reproductive system in relation to the uterus, and the corresponding molecular mechanisms that have been studied. In addition, this review will outline the state of knowledge of EDC epigenetic regulation in the uterus and how it impacts reproductive health, as well as identify areas for future research.

Bisphenol A (BPA) is a well-known endocrine-disrupting chemical (EDC) that has been implicated in cancer development. However, the specific mechanisms of EDCs, including BPA, remain unclear. Voltage-gated potassium (Kv) channels have been closely related to cancer. In particular, Kv3.4 plays a role in cancer malignancy, including cell migration via the ERK and AKT signaling pathways. In this study, we investigated the mechanism of BPA in relation to Kv3.4 expression in human breast cancer MCF7 cells. BPA treatment significantly increased Kv3.4 expression at both the mRNA and protein levels and induced cell migration. Further analysis demonstrated that Kv3.4 is closely related to integrin β and integrin-regulated FAK signaling. However, BPA-induced cell migration and integrin-regulated FAK signaling were significantly abolished by Kv3.4 silencing. Therefore, we concluded that BPA is closely associated with cancer cell migration mediated by Kv3.4 via integrin-regulated FAK signaling. These findings provide novel insights into the role of BPA in cancer progression and suggest Kv3.4 as a potential therapeutic target for BPA-associated cell migration.

Phenols, widespread environmental chemicals, may influence neurodevelopment, but their association with dyslexia remains poorly understood. This case-control study, part of the Tongji Reading Environment and Dyslexia Research Project, included 1,062 children. We measured urinary levels of three bisphenols, three benzophenones, and two antimicrobials, and constructed a dyslexia-specific polygenic risk score (PRS) using genome-wide association study data. Conditional logistic regression assessed the relationship between phenol exposure and dyslexia risk. Participants were stratified into four groups based on median phenol exposure and PRS levels to examine the modifying role of genetic susceptibility. Phenol compounds were detected in most urine samples. Elevated urinary bisphenol A (BPA) levels were significantly associated with increased dyslexia risk (OR = 1.23, 95% CI: 1.03-1.46), particularly in girls. Children with high PRS and high BPA exposure had a substantially higher dyslexia risk (OR = 1.70, 95% CI: 1.05-2.76) compared to those with low PRS and low BPA exposure. However, no significant interaction was observed between PRS and BPA exposure. These findings emphasize the importance of reducing BPA exposure as a potential preventive measure and highlight the need for further research to elucidate causal pathways and mechanisms underlying these associations.

This systematic review and meta-analysis synthesizes current literature examining the relationship between phthalate exposure and reproductive health in patients undergoing assisted reproductive treatment (ART). We conducted a comprehensive search across multiple databases, including PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), China Science and Technology Journal Database (VIP), and Wanfang databases. From 16 relevant publications identified, five studies were included in the systematic review and 11 in the meta-analysis. Our findings indicate that most of the 18 phthalate metabolites analyzed demonstrated negative associations with reproductive health outcomes in ART patients. High molecular weight phthalates, particularly mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), were most frequently linked to adverse outcomes, followed by metabolites such as mono-isobutyl phthalate (MiBP), mono-benzyl phthalate (MBzP). Both high and low molecular weight phthalates, including monoethyl phthalate (MEP) and MiBP, were correlated with negative reproductive outcomes. However, no significant associations were observed between mono-2-ethyl-5-hydroxyhexyl terephthalate (MEHHTP) or mono-3-hydroxybutyl phthalate (MHBP) and reproductive health parameters. Our analysis suggests that phthalate exposure may adversely affect fertility, hormone levels, and gamete quality, while also being associated with pregnancy complications and oxidative stress. These findings underscore the need for further large-scale studies to confirm these relationships and their clinical implications.

Female fertility and reproductive health depend on a series of developmental steps from embryogenesis through puberty, in addition to the proper functioning of the reproductive system in adulthood. Two important steps are the establishment of the ovarian reserve and development of the hypothalamic-pituitary-ovarian axis. During reproductive years, maintaining an adequate ovarian reserve of follicles as well as balanced neuroendocrine control of reproductive organs is crucial for fertility. Dysregulation of either of these events, during development or in adulthood, can lead to reproductive disorders. Over the past five decades, human fertility rates have declined, whereas the incidence of female reproductive disorders has risen, trends partially linked to environmental factors such as exposure to endocrine-disrupting chemicals (EDCs). Here we outline epidemiological and mechanistic evidence for how EDCs affect the ovarian reserve during early development, its maintenance during adulthood and the establishment of the hypothalamic-pituitary control of puberty and ovulation. Our Review not only reveals strong support for the role of EDC exposure in the development of female reproductive disorders such as abnormal puberty, impaired fertility, premature menopause or polycystic ovarian syndrome, but also highlights knowledge gaps, including the difficulty to prove causality between exposure and human disease manifestation.

Endocrine-disrupting chemicals (EDCs) are natural or synthetic compounds that are ubiquitous in the environment and in daily-usage products and interfere with the normal function of the endocrine system leading to adverse health effects in humans. Exposure to these chemicals might elevate the risk of metabolic disorders, developmental and reproductive defects, and endocrine-related cancers. Prostate cancer is the most common hormone-dependent cancer in men, and the fifth leading cause of cancer-related mortality, partly owing to a lack of knowledge about the mechanisms that lead to aggressive castration-resistant forms. In addition to the dependence of early-stage prostate cancer on androgen actions, the prostate is a target of oestrogenic regulation. This hormone dependence, along with the fact that exogenous influences are major risk factors for prostate cancer, make the prostate a likely target of harmful actions from EDCs. Various sources of EDCs and their different modes of action might explain their role in prostate carcinogenesis.

Polycystic ovarian syndrome (PCOS) is a common female endocrinologic condition that affects both the metabolic and reproductive systems and is the most frequent cause of anovulatory infertility. It is also associated with a range of psychiatric outcomes in individuals, including bulimia nervosa, schizophrenia, bipolar disorder, depression, anxiety, and personality disorders. At the same time, evidence suggests that hyperandrogenism, the characteristic trait of PCOS, may impair fetal neurodevelopment. Epidemiological studies have linked maternal PCOS with a variety of behavioral and psychiatric conditions in offspring including autism spectrum disorder and attention deficit hyperactivity disorder. In this review, we explore evidence for potential underlying biological mechanisms that might explain these observed associations, discuss the complex interplay between genetics and various environmental factors across generations, and highlight avenues for future research.

With plant-based (PB) diets gaining popularity, ultraprocessed novel plant-based foods (NPBFs) are an increasingly available alternative to animal-based foods (ABFs). The degree of industrial food processing has been associated with higher organophosphorus flame retardant (PFR) and plasticizer contamination. Here, the occurrence of these contaminants in NPBFs was investigated by using liquid chromatography-tandem mass spectrometry. Our findings show differences in contamination levels and patterns between PB food categories, with PB cheese-alternatives showing the highest levels of both total PFRs (mean: 123 ng/g ww) and total plasticizers (mean: 1155 ng/g ww). The results further point to food contact material and industrial processing as possible contamination sources. Compared with previous studies of ABFs, NPBFs generally showed higher contamination levels, leading to a higher dietary exposure in a vegan diet scenario. While the adult population is not at immediate risk following NPBF consumption, based on these results, a direct replacement of all ABFs with NPBFs is not recommended. Additionally, it is suggested that different PB food categories be included in future food studies monitoring dietary exposure.

Phthalates, a group of synthetic non-persistent organic chemicals commonly used as solvents and plasticisers, have been associated with a range of detrimental health effects. These endocrine disrupting chemicals (ECDs) may exert their effects through epigenetic changes such as altered microRNA (miRNA) expression. miRNAs are short non-coding endogenous RNA transcripts that are preferentially expressed in various tissues and cell types and can circulate in body fluids, thereby regulating gene expression and acting as mediators for intercellular communication. As miRNAs mostly target protein-coding transcripts, they are involved in nearly all networks that regulate developmental and pathological processes. In this review, we provide an overview of human, in vivo and in vitro studies assessing altered miRNA expression due to phthalate exposure and their biological effects. Importantly, this study suggests that the mechanism of phthalate action may in part be mediated by epigenetic changes, affecting a large number of different proteins. This is indicative that alterations in miRNA expression induced by phthalate exposure are then implicated in a wide range of health conditions, including reproductive dysfunction, oncogenesis, metabolic disorders, and neurodevelopmental outcomes. Exposure to phthalates and their metabolites predominantly results in the upregulation of miRNAs. Dysregulation of miR-34a, miR-15b, miR-141, miR-184, miR-19a, miR-125, and miR-let-7 were observed across several studies. More research involving human participants combined with mechanistic studies integrating mRNA target analysis would be beneficial in understanding the downstream effects of phthalate exposure on gene expression and grasping the broader biological implications.

Prenatal phthalate exposure is associated with adverse neurodevelopmental outcomes, yet data on impacts of early life exposure remains limited. We investigated phthalate and replacement plasticizer exposures from 2 weeks to 7 years of age in relation to brain anatomical attributes, using serial structural magnetic resonance imaging (sMRI).

Children were enrolled after birth into the UNC Baby Connectome Project, a longitudinal neuroimaging study (North Carolina, USA; 2017-2020). Urine samples (n = 406) were collected at each visit and analyzed for 17 phthalate and replacement plasticizer metabolites. Among 157 children contributing 369 sMRIs, we calculated metabolite-specific average exposures across each individual's urine samples and used linear mixed models to estimate longitudinal associations of log transformed, specific gravity-adjusted average metabolite concentrations with gray and white matter volume, and cortical volume, thickness, and surface area. We examined sex-specific differences in these associations.

Higher average metabolite concentration was associated with lower gray matter volume (MCPP: (-1.73 cm3, 95 % CI: -3.36, -0.10) and higher white matter volume (∑DEHP: 2.28 cm3, 95 % CI: 0.08, 4.48). Among boys (n = 72, 140 sMRIs), MEP (-2.97 cm3, 95 % CI: -5.85, -0.09) and MiBP (-2.40 cm3, 95 % CI: -4.64, -0.15) were also associated with lower gray matter volume. Among females (n = 85, 229 MRIs), higher ∑DINCH exposure was associated with higher white matter volume (2.27 cm3, 95 % CI: 0.29, 4.25). We observed significant sex interactions for ∑DEHP with gray matter (p-interaction = 0.03) and ∑DINCH with white matter volume (p-interaction = 0.001).

Early life phthalate/plasticizer exposure may differentially impact various brain region volumes in early childhood, with potential downstream consequences on functional development.

Precocious puberty is characterized by early sexual maturation in children before 8 years in girls and 9 years in boys. While puberty is initiated by the activation of the hypothalamic-pituitary-gonadal axis, precise mechanisms triggering the early activation of this axis in children with central precocious puberty (CPP) remain elusive. Here, we aimed to identify variables that may influence the risk of CPP. This retrospective cohort study utilized data from the Korean National Health Insurance Service and National Health Screening Program for Infants and Children and included 43,952 children with CPP and 854,749 controls. Participants were followed up until 2020 for CPP development to determine their height, weight, and head circumference measurements, as well as evaluate their physiological, emotional, cognitive, and social development. The birth weights for boys and girls with CPP were 0.09 and 0.06 kg lower than those of controls, respectively. Breastfeeding rates for children with CPP were lower than those for controls. Children with low birth weights (boys: odds ratio [OR] = 1.71, P < 0.0001; girls: OR 1.30, P < 0.0001) and those who were overweight (boys: OR 1.33, P = 0.0006; girls: OR 1.30, P < 0.0001) or obese (boys: OR 1.60, P < 0.0001; girls: OR 1.14, P < 0.0001) were more likely to develop CPP. Breastfeeding exerted a significant protective effect against CPP in girls (OR 0.95, P = 0.0003). Low birth weight and high body mass index were associated with CPP development.

Many products including plastic food containers, medical tubing, and personal care products contain phthalate diesters. Phthalates have been shown to negatively affect the female reproductive system. However, the ovarian cellular impacts of monoester phthalates, the metabolites of phthalate diesters, are largely unknown. This study tested the hypothesis that a monophthalate metabolite mixture or single monophthalate affects cell energy metabolism in granulosa cells. To test this hypothesis, granulosa cells were exposed to vehicle control, the mean urinary level and 100-fold higher monophthalate mixture (2.0 µM and 200.0 µM), or mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) (0.22 µM and 22.0 µM) for 24 or 72 h. Gene expression was assessed for antioxidant enzymes, glycolytic enzymes, and glucose transporters. Cellular metabolism was assessed by Agilent Seahorse assays. MEHHP did not alter expression of the antioxidant enzymes, glycolytic enzymes, or glucose transporters compared to control. However, the monophthalate mixture significantly increased expression of Ldha (200.0 µM, 72-hour exposure) and Glut1 (2.0 µM, 24-hour exposure) compared to control. MEHHP (22.0 µM) increased total ATP production rate at 24 h compared to control, but did not change total ATP production after 72 h. Further, the mixture (2.0 µM and 200.0 µM) altered total ATP production rates compared to control at the 72-hour and 24-hour time points. Short-term phthalate exposure led to significant effects on ATP production rates, making this endpoint a logical indicator of early phthalate toxicity. These data indicate that a monophthalate mixture as well as single monophthalate exposure alter cellular metabolism in granulosa cells.

Novel bisphenol S (BPS) derivatives are being increasingly utilized as substitutes to bisphenol A (BPA) and BPS in thermal receipts and other industrial or commercial products. In recent years, the environmental occurrence, human exposure, and toxicity of non-chlorinated and chlorinated BPS derivatives have been investigated in numerous studies. This review summarizes the state-of-art and new knowledge on these aspects and provides recommendations for future research directions. The environmental analysis showed that BPS derivatives have been widely detected in paper products, water, indoor dust, sediment, and municipal sewage sludge. Recent studies have also reported the presence of non-chlorinated BPS derivatives, such as benzenesulfonylbenzene (DDS) and 4-(4-propan-2-yloxyphenyl)sulfonylphenol (BPSIP), in human breast milk, urine, and the maternal-fetal-placental unit. Toxicological studies suggest that BPS derivatives may cause a series of toxic effects, including endocrine-disrupting effects, cytotoxicity, hepatotoxicity, developmental toxicity, and neurotoxicity, some of which have been shown to exhibit adverse effects similar to or even greater than those of BPS. Future studies should focus on elucidating environmental occurrences, half-lives, sources for human exposure, and potential transformation pathways of BPS derivatives, as well as their toxic effects and underlying mechanisms.

Humans are widely exposed to synthetic chemicals, especially via food. The types of chemical contaminants in food (including food contact chemicals) are diverse, and many of these are known to be hazardous, with mounting evidence that some contribute to noncommunicable diseases. The increasing consumption of ultra-processed foods, which contain synthetic chemicals, also contributes to adverse health. If the chemical contamination of foods were better characterized, then this issue would likely receive more attention as an important opportunity for disease prevention. In this Review, we discuss types and sources of synthetic food contaminants, focusing on food contact chemicals and their presence in ultra-processed foods. We outline future research needs and highlight possible responses at different food system levels. A sustainable transition of the food system must address the health impacts of synthetic chemicals in food; we discuss existing solutions that do justice to the complexity of the issue while avoiding regrettable substitutions and rebound effects.

Early-life exposure to endocrine-disrupting chemicals, such as phenols and phthalates, is suspected to impact various dimensions of child health. Using a multi-outcome approach, this study aimed to estimate their cumulative effect on the child cardiometabolic, respiratory and neurodevelopmental health.

In 373 children of 3 years old from the SEPAGES cohort, a multi-domain health score was built from twenty-three health parameters. Fourteen metabolites of parabens, phenols, and phthalate/DINCH were measured several times during pregnancy (trimester 2 and 3) and infancy (2 and 12 months of age). Two mixture models, quantile g computation (q-gcomp) and Bayesian Kernel Machine Regression (BKMR), estimated associations between increased concentration of parabens, phenols, and phthalates/DINCH and the child health score.

Q-gcomp showed that the paraben mixture and the phthalate mixture were associated with a poorer health score (β = -0.11, 95% Confidence Interval (CI): -0.22, 0.00; β = -0.14, 95% CI: -0.27, -0.01, respectively), while no significant association was found for the mixture of phenols (β = -0.06, 95% CI: -0.18, 0.06). A trend for an association was observed between the whole mixture (parabens, phenols and phthalates combined) with a poorer health score (β = -0.14, 95% CI: -0.32, 0.04). Similar patterns of association, while subject to large uncertainty, have been observed with BKMR.

This study provides further evidence for the adverse health effects of early-life exposure to parabens and phthalates. Based on their potential impact on multiple areas of child health, public health policies targeting these chemical compounds are recommended.

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.

There is significant interest in combining adverse outcome pathways (AOPs) with Bayesian networks (BNs) because of their shared representation using directed acyclic graphs (DAGs). However, it has not been verified empirically whether AOP networks are mathematically congruent with BNs. Furthermore, important properties for BNs, such as Markov blankets, have not been emphasized, which is a missed opportunity for simplifying and optimizing the model. Here, we summarize the connection between AOP networks and BNs and explore the implications for toxicity modeling. We also present a case study in drug-related liver toxicity. Our results confirm that AOP networks are congruent mathematically with BNs, with incorporation of the mathematical properties of BN leading to significantly simplified and more efficient models.

New evidence has emerged that plastic polymers and their chemical additives, particularly di-2-ethylhexylphthalate (DEHP), contribute to cardiovascular disease (CVD). Phthalates are commonly used in the production of plastic materials and have been linked to increased oxidative stress, metabolic dysfunction, and cardiovascular disease. Estimates of phthalate-attributable cardiovascular mortality have been made for the US, but global estimates are needed to inform ongoing negotiations of a Global Plastics Treaty.

Cardiovascular mortality data from the Institute for Health Metrics and Evaluation (IHME) and regional DEHP exposure estimates from several sources were used to estimate burden. Hazard ratios of CV mortality were calculated using published exposure estimates, and country-level cardiovascular mortality rates were used to calculate excess deaths and years of life lost (YLL) due to DEHP exposure.

In 2018, an estimated 356,238 deaths globally were attributed to DEHP exposure, representing 13.497% of all cardiovascular deaths among individuals aged 55-64. Of these, 349,113 were attributed to the use of plastics. Geographic disparities were evident, with South Asia and the Middle East suffering the greatest percentage of cardiovascular deaths attributable to DEHP exposure (16.807%). The Middle East, South Asia, East Asia, and the Pacific accounted for the largest shares of DEHP-attributable CVD deaths (73.163%). Globally, DEHP resulted in 10.473 million YLL.

Plastics pose a significant risk to increased cardiovascular mortality, disproportionately impacting regions which have developing plastic production sectors. The findings underscore the need for urgent global and local regulatory interventions to kerb mortality from DEHP exposure.

Bloomberg Philanthropies and the National Institutes of Health.

Human biomonitoring (HBM) is a critical scientific tool for assessing human exposure by quantifying chemicals and their metabolites in biological specimens such as blood and urine. This approach provides a comprehensive and accurate evaluation of internal exposures from diverse sources and exposure routes. In Ireland, establishing a national HBM programme requires a systematic chemical prioritisation process that aligns global frameworks with local public perceptions. This study integrates insights from international initiatives such as the European Joint Programme Human Biomonitoring for Europe (HBM4EU) and the Partnership for the Assessment of Risks from Chemicals (PARC)-along with HBM programmes from EU countries (Germany, France, Belgium, Norway, Slovenia, Czech Republic, and Sweden) and non-EU countries (US, Canada, South Korea, China, and New Zealand). In addition, a national survey was conducted to capture the perceptions of people in Ireland regarding chemicals of concern to develop a comprehensive priority list of chemicals and biomarkers. The broader chemical groups identified include heavy metals (lead, cadmium, mercury, arsenic, and chromium VI), plasticisers (phthalates), bisphenols, pesticides, flame retardants, PFASs (per- and polyfluoroalkyl substances), PAHs (polycyclic aromatic hydrocarbons), POPs (persistent organic compounds), VOCs (volatile organic compounds), and UV (ultraviolet) filters. This integrated, participatory approach provides a roadmap for a robust, adaptable chemical list that supports evidence-based policy decisions in HBM in Ireland and enhances public health outcomes.

Sex ratio at birth (SRB) is a simple, noninvasive way to monitor the reproductive health of a population. Apparently only a few studies have assessed the relationship between ambient air pollution and SRBs. The studies that investigated this relationship have yielded inconsistent results. Ambient air pollution levels, including particulate matter (PM2.5) levels, have decreased in Taipei city after a mass rapid transit (MRT) system commenced operations in 1996. The aim of this study was to determine whether the changes in levels of PM2.5 after the implementation of the MRT system in Taipei may have influenced the concurrent alterations noted in the SRB. In order to assess this potential association, annual numbers of male and female births were obtained from Taiwan's Department of Household Registration, Ministry of Interior Affairs from 1992 to 2023. Mean yearly SRBs were calculated for 4 time periods, 1992-1995, 1996-2004, 2005-2015, and 2016-2023. Linear logistic regression was employed to evaluate the variation in officially reported PM2.5 levels during those periods and alterations in the ratios. The ratios for time periods 1 to 4 were 52.61%, 52.22%, 51.78%, and 51.67%, respectively. Compared to Period 1 (pre-MRT), the odds ratios for Periods 2, 3, and 4 were 0.98 (0.97-0.99), 0.97 (0.96-0.98), and 0.96 (0.95-0.98), respectively. The trend toward the decreased SRB was found to be gradual but significant.

Small benthic scavengers and carnivores, such as polychaetes, are very interesting to assess the accumulation and transfer of microplastics (MPs) to higher trophic levels in marine ecosystems. In this study we evaluate the presence, accumulation and impacts of MPs in the North-Atlantic deep-sea polychaete Laetmonice filicornis. Three types of MPs were identified: fishing lines, fibres and fragments, mostly black in colour, followed by red and blue ones. The average number of MPs was 4.10 ± 1.90 particles/g tissue. Fibres were the most abundant. They were composed of Polypropylene, Rayon, Polyethyleneimine Cellulose and Polyester. The histological analysis revealed the presence of microfibres embedded in muscles, peritoneum, nephridia, gonads and blood vessels, which can have a direct impact on vital functions, such as feeding and reproduction. This species occupies both predator and prey roles, bioaccumulate MPs and can transfer them to higher trophic links, representing a significant threat to all marine species, including humans.

Polychlorinated biphenyls (PCBs) are a group of environmental toxicants associated with increased risk of diabetes, obesity, and metabolic syndrome. These metabolic disorders are characterized by systemic and local inflammation within adipose tissue, the primary site of PCB accumulation. These inflammatory changes arise when resident adipose tissue macrophages undergo phenotypic plasticity-switching from an antiinflammatory to an inflammatory phenotype. Thus, we sought to assess whether PCB exposure drives macrophage phenotypic switching. We investigated how human monocyte-derived macrophages polarized toward an M1, M2a, or M2c phenotype were impacted by exposure to Aroclor 1254, a PCB mixture found at high levels in school air. We showed that PCB exposure not only exacerbates the inflammatory phenotype of M1 macrophages but also shifts both M2a and M2c cells toward a more inflammatory phototype in both a dose- and time-dependent manner. Additionally, we show that PCB exposure leads to significant metabolic changes. M2 macrophages exposed to PCBs exhibit increased reliance on aerobic glycolysis and reduced capacity for fatty acid and amino acid oxidation-both indicators of an inflammatory macrophage phenotype. Collectively, these results demonstrate that PCBs promote immunometabolic macrophage plasticity toward a more M1-like phenotype, thereby suggesting that PCBs exacerbate metabolic diseases by altering the inflammatory environment in adipose tissue.

Pentachlorophenol (PCP), a persistent organic pollutant, has endocrine disrupting properties and there may be a link between its exposure and reproductive outcomes. In this study, we assessed the relationship of PCP exposure levels with ovarian reserve markers and reproductive health outcomes in women (N = 656) undergoing in vitro fertilization (IVF). PCP concentrations were determined in urine (n = 1968; repeated measures) and follicular fluid samples (n = 603). Generalized linear models or generalized estimating equations were used to analyze adjusted association between PCP exposure and selected outcomes (ovarian reserve and IVF outcomes among the women). The median concentration of PCP in the follicular fluid (1.38 ng/mL) was significantly higher compared with that in the urine (specific gravity-adjusted: 0.79 ng/mL). We observed that the urinary PCP concentrations were significantly associated with increased estradiol levels (12.4%; 95% CI: 0.76, 25.4%) but decreased total oocyte yield (-8.35%; 95% CI: -9.64, -7.04%), mature oocytes (-12.0%; 95% CI: -13.4, -10.6%), and fertilization proportion (-2.98%; 95% CI: -5.51, -0.39%). Moreover, there were significant associations of follicular fluid PCP concentrations with declines in the total oocyte yield (-10.6%; 95% CI: -11.9, -9.26%), mature oocytes (-10.6%; 95% CI: -12.0, -9.09%), and proportions of fertilization (-3.75%; 95% CI: -6.39, -1.03%), blastocyst formation (-8.01%; 95% CI: -16.6, -0.37%), and usable blastocysts (-13.9%; 95% CI: -23.6, -3.03%). Our results revealed that exposure to PCP was related with impaired reproductive outcomes of IVF, while additional research is needed to confirm the findings and clarify the underlying mechanisms.

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.

Biologists are increasingly documenting anthropogenic disruptions, both at the organism and ecosystem levels, indicating that these disruptions are a fundamental, qualitative component of the Anthropocene. Nonetheless, the notion of disruption has yet to be theorized. Informally, disruptions are direct or indirect consequences of specific causes that impair the contribution of parts of living systems to their ability to last over time. To progress in this theorization, we work here on a particular case. Even relatively minor temperature changes can significantly impact plant-pollinator synchrony, disrupting mutualistic interaction networks. Understanding this phenomenon requires a specific rationale since models describing it use both historical and systemic reasoning. Specifically, history justifies that the ecosystem initially exists in a very narrow part of the possibility space where all its populations are viable, and the disruption leads to a more generic configuration where some populations are not viable. Building on this rationale, we develop a mathematical schema inspired by Boltzmann's entropy, apply it to this situation, and provide a technical definition of disruption.

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.

The effects of bisphenol A (BPA), a highly diffused endocrine-disrupting chemical found mainly in plastics, on neural circuits and behaviors are well-known. However, the effects of its substitutes have not been fully investigated. Thus, in the present study, we compare the effects of perinatal exposure to bisphenol A or S (BPS) on reproductive behaviors and related hypothalamic kisspeptin system in mice. C57BL/6J dams were orally treated with 4 μg/kg body weight/day of BPA, BPS, or vehicle from mating until the weaning of the offspring. In the adult offspring, we performed the two-bedding T-Maze test, and we observed the spontaneous sexual behavior. Exposure to BPA caused a delay in puberty onset in females, while BPS caused anticipation in males, and both altered the estrous cycle in females. The sexual and sexual-related behaviors were partially altered in males, especially in the BPA-exposed ones. Regarding the kisspeptin immunoreactivity in the analyzed hypothalamic nuclei, in BPA- or BPS-treated females, we observed an increase within the rostral periventricular area, while BPA led to an increase in the paraventricular nucleus, and BPS induced a reduction compared to control females. Among males, we observed a significant increase in the arcuate nucleus of BPA-treated males and a significant decrease in the paraventricular nucleus of BPS-treated ones. These results support the idea that perinatal exposure to low doses of either BPA or BPS is altering, in a sexually differentiated way, some reproductive-relevant parameters, sexual behaviors, and kisspeptin hypothalamic nuclei.

Medium-chain chlorinated paraffins (MCCPs) are among the most prevalent chemicals detected in human serum. As an emerging persistent organic pollutant, their toxicity mechanisms, particularly concerning the female reproductive system, remain poorly understood. In this study, we present both in vivo and in vitro evidence of ovarian toxicity induced by MCCPs and insights into their underlying molecular mechanisms. MCCP exposure induced chromatin condensation in the nucleus and mitochondria vacuolization of ovarian granulosa cells in rats and significantly increased the levels of serum gonadotropins and sex hormones, while reducing gonadotropin-releasing hormone levels. Transcriptomics analysis of ovaries revealed a predominant effect of MCCPs on the cell cycle, oocyte meiosis, and DNA damage repair pathways. Moreover, dual-omics integrative analysis indicated significant disturbance of steroid hormone biosynthesis caused by MCCPs, as well as amino acid metabolism related to TCA cycle. Furthermore, in vitro assays demonstrated that MCCP exposure disrupts intracellular Ca2+ homeostasis and generates reactive oxygen species, ultimately leading to DNA damage. In conclusion, this study revealed potential mechanisms by which MCCPs affect ovary function. These findings can provide valuable insights for the mechanism-based risk assessment of MCCPs on female reproduction.

This study explores the endocrine-disrupting effects of climbazole (CBZ), an environmental and lifestyle stressor, on male fertility. The impact of CBZ on sperm vitality, motility, and molecular pathways related to hormone receptors and apoptosis was evaluated, in non-capacitated and capacitated conditions. Gene expression of key components, including hormone receptors (ESR1, ESR2, FSHR, AR), apoptosis-related genes (BAX, BCL2), and COX4l1 (involved in mitochondrial function), was analyzed. Protein tyrosine phosphorylation, a marker of capacitation, was also examined using immunofluorescence and Western blot analysis. We demonstrated that CBZ significantly reduced sperm vitality at concentrations above 25 µM and motility at 1 and 10 µM in non-capacitated and capacitated conditions. Changes in tyrosine phosphorylation patterns were also observed. Gene expression analysis revealed an upregulation of ESR1, ESR2, FSHR, and BAX, while AR and COX4l1 expression were downregulated. These findings offer new insights into the potential endocrine-disrupting and cytotoxic effects of CBZ, highlighting its potential role in compromising male reproductive health.

The increasing prevalence of pediatric obesity has emerged as a significant public health concern. Among various contributing factors, exposure to endocrine-disrupting chemicals (EDCs) has gained recognition for its potential role. EDCs, including bisphenols, phthalates, per- and polyfluoroalkyl substances, polycyclic aromatic hydrocarbons, and organochlorines, disrupt hormonal regulation and metabolic processes, contributing to alterations in fat storage, appetite regulation, and insulin sensitivity. This study offers a comprehensive review of the current research linking EDC exposure to pediatric obesity by integrating the findings from experimental and epidemiological studies. It also addresses the complexities of interpreting this evidence in the context of public health, highlighting the urgent need for further research.

As a prevalent industrial material and component of consumer products, bisphenol A (BPA) is linked to hormone homeostasis disruption and potential carcinogenicity. However, the precise mechanisms through which BPA contributes to thyroid carcinogenesis, especially in papillary thyroid carcinoma (PTC), are not fully understood. This study investigates how BPA boosts the proliferation and tumorigenic characteristics of thyroid cells. BPA exposure significantly increased cell proliferation in a duration-dependent manner at a concentration of 0.5 μM, which is slightly higher than human exposure levels. Therefore, this study utilized BPA treatment concentrations of 0.1 µM and 0.5 µM. BPA augmented the invasiveness of PTC cells with a dependency on both dosage and temporal factors. RNA-seq and gene expression analysis from normal human thyroid follicular epithelial cells suggested that BPA upregulated genes related to oxidative stress and thyroid cancer. Concurrently, our study revealed significant upregulation of NOX4 in thyroid tumors compared to normal thyroid tissues, with higher expression levels observed in advanced carcinomas by analyses of the TCGA database. BPA induces the upregulation of NOX4 in human thyroid cells, thereby triggering the activation of MAPK and PI3K/AKT pathways. In xenograft models, BPA treatment resulted in increased tumor size and Ki-67 proliferation index, accompanied by upregulated NOX4 expression. Additionally, BPA exposure led to higher levels of free triiodothyronine (FT3), indicating thyroid hormone disruption. Mechanistically, BPA activates the MAPK and PI3K/AKT pathways via NOX4, leading to increased ROS production and cell proliferation. This was further demonstrated through the use of ROS scavenger treatment and si-NOX4, which showed that BPA stimulates ROS generation by activating NOX4/MAPK and NOX4/PI3K/AKT pathways in thyroid cells. This finding enhances our understanding of the pathogenesis of PTC related to BPA exposure and highlights the necessity for rigorous health risk assessments regarding BPA exposure.