Endocrine Disruptors

Microplastics and nanoplastics (<5 mm and <1 μm, respectively) are emerging contaminants now ubiquitous across environmental matrices and increasingly recognized for their impacts on human health. These particles commonly adsorb or contain endocrine-disrupting chemicals-such as bisphenol-A and phthalate additives-that together trigger complex biological responses. This review examines the central role of oxidative stress in mediating the toxicity of microplastics and associated endocrine disruptors across multiple organ systems. We discuss mechanisms including cellular uptake, reactive oxygen species generation, mitochondrial dysfunction, impairment of antioxidant defenses, and activation of key signaling pathways. Organ-specific effects on reproductive health, cardiovascular function, hepatic metabolism, gut barrier integrity, and neurological systems are highlighted. Current evidence strongly supports oxidative stress as a pivotal mechanism linking microplastic exposure to systemic toxicity, underscoring important implications for public health policy and clinical intervention strategies.

BackgroundEnvironmental endocrine disruptors (EEDs) including heavy metals, plasticizers, and persistent organic pollutants have been increasingly linked to declining male reproductive health globally. While epidemiological associations are well-established, the underlying molecular mechanisms and long-term consequences require systematic evaluation.ObjectivesThis review synthesizes current evidence on EED impacts on male reproductive health, focusing on molecular mechanisms, population-based evidence, transgenerational effects, and intervention strategies.MethodsWe conducted comprehensive literature searches across PubMed, Web of Science, and Scopus (2019-2024) to identify peer-reviewed studies on EED reproductive toxicity, including mechanistic investigations, epidemiological studies, and intervention research.ResultsEEDs disrupt male reproduction through multiple pathways: androgen and estrogen receptor interference, oxidative stress induction, mitochondrial dysfunction, and epigenetic modifications. Population studies demonstrate consistent associations between EED exposure and reduced sperm quality, with effect sizes varying by exposure level and chemical type. Animal studies provide compelling evidence for transgenerational inheritance of reproductive dysfunction through epigenetic mechanisms, though human evidence remains limited. Workplace protection measures, environmental remediation, and policy interventions show promise but require broader implementation.ConclusionsEEDs pose significant threats to male reproductive health through complex, interconnected mechanisms. While substantial progress has been made in understanding these effects, critical gaps remain in mixture toxicology, low-dose effects, and transgenerational impacts in humans. Enhanced biomonitoring, mechanism-based interventions, and strengthened regulatory frameworks are essential for protecting current and future reproductive health.

Endocrine-disrupting chemicals (EDCs) are a group of substances that can alter normal body functioning by disrupting the various patterns of hormone secretion and action. Some of these substances are used as plasticizers (e.g., bisphenols and phthalates) and agrochemicals (e.g., vinclozolin). EDC exposure can occur by many routes, including oral by contaminated food and water, through the skin, inhalation, and by placental transfer from mother to fetus or mother to infant (via lactation). The increase in EDCs used by the industry has strongly impacted our health. An increasing number of scientific works have reported the effects of EDCs on cancer development, metabolism, heart disease, and fertility. Most recently, studies on EDCs effects on behavior and the developing brain are raising major concerns related to the formation of sex differences and to the increased prevalence of neuropsychiatric disorders. In this review, we highlight the recent findings of the effects of pre-, peri-, and postnatal exposure to the three well-studied EDCs (i.e., bisphenols (BPA, BPS, BPF, and BPAF), phthalates (DBP, BBP, DEHP, and DiPeP), and vinclozolin (VIN)) on developing brain and behavior across generations in experimental animals.

Endometrial cancer (EC) is a hormone-dependent malignancy whose global incidence is steadily rising. Increasing evidence suggests that exposure to endocrine-disrupting chemicals (EDCs) may contribute to EC development through interference with hormonal signaling mediated by estrogen receptors (ER). This systematic review aimed to synthesize the available epidemiological evidence on the association between exposure to EDCs and the risk of EC. A comprehensive search of MEDLINE, EMBASE, Scopus, the Cochrane Library, and ClinicalTrials.gov was conducted up to April 2025, following PRISMA 2020 recommendations. Eligible studies included observational or interventional designs assessing quantified exposure to EDCs and EC incidence or risk. Eight studies met the inclusion criteria (five case-control, two cohort, and one randomized controlled trial), comprising 2, 609 EC cases and 1, 577 controls. Cadmium emerged as the EDC most frequently associated with EC, reported in five studies, four of which demonstrated a significant positive association, particularly among lean postmenopausal women. In contrast, evidence regarding bisphenol A (BPA) and its metabolites was inconsistent: only mono-n-butyl phthalate (MnBP) showed a positive correlation with EC in one study, while BPA and dibutyl phthalate (DBP) did not. Nonylphenol and octylphenol were also found to be positively associated with EC risk in a single study. Conversely, neither lead exposure nor dietary intake of isoflavones was associated with EC incidence. Overall, available epidemiological evidence supports a potential association between cadmium exposure and increased EC risk, while data for other EDCs remain limited and inconclusive. Substantial heterogeneity in exposure assessment, study design, and confounder adjustment limits comparability across studies and precludes definitive conclusions. Further well-designed longitudinal studies with standardized and repeated exposure measurements are needed to clarify causal relationships between EDC exposure and endometrial carcinogenesis.Systematic review registrationhttps://inplasy.com/inplasy-2025-6-0030/, identifier INPLASY202560030.