Aug 2026· International Journal of Molecular Sciences· Vol 27· 0 citations· 192 references
Medicine
TL;DR
Improved integration of toxicological and epidemiological evidence will strengthen causal inference, refine hazard characterization, and support more protective regulatory strategies for reducing the human health burden associated with endocrine-disrupting pesticides worldwide.
Abstract
Endocrine-disrupting pesticides (EDPs) are environmental toxicants capable of perturbing hormonal homeostasis through multiple molecular and cellular mechanisms. Growing evidence indicates that these compounds contribute to a broad spectrum of adverse health outcomes extending beyond classical endocrine dysfunction. This review critically synthesizes current knowledge on the toxicological mechanisms of EDPs and evaluates epidemiological evidence linking exposure to human disease. Mechanistically, EDPs act through modulation of nuclear hormone receptors, disruption of membrane-associated signaling pathways, interference with hormone synthesis, metabolism, and transport, induction of oxidative stress and mitochondrial dysfunction, and epigenetic reprogramming. These molecular events converge on shared biological pathways that affect multiple organ systems and life stages. Human and experimental evidence associates EDP exposure with reproductive dysfunction, endocrine-related cancers, metabolic disorders, thyroid abnormalities, and neurodevelopmental impairments. Particular concern surrounds exposure during critical windows of susceptibility, especially prenatal development and early childhood, when endocrine systems are highly vulnerable to disruption and developmental programming. Across disease endpoints, recurring mechanisms, including endocrine receptor perturbation, oxidative stress, inflammation, and epigenetic alterations, support a unifying toxicological framework linking diverse adverse outcomes. Despite substantial progress, important uncertainties remain regarding chronic low-dose exposure, non-monotonic dose–response relationships, cumulative effects of pesticide mixtures, and the translation of mechanistic findings into human risk assessment. Future research should integrate repeated biomonitoring, advanced mixture modeling, mechanistic biomarkers, and multi-omics approaches within longitudinal life-course studies. Improved integration of toxicological and epidemiological evidence will strengthen causal inference, refine hazard characterization, and support more protective regulatory strategies for reducing the human health burden associated with endocrine-disrupting pesticides worldwide.
Endocrine-disrupting pesticides (EDPs) exert deleterious effects on the endocrine system, with documented evidence implicating specific pesticides in endocrine disruption, resulting in developmental delays during puberty and thyroid gland dysfunction, thereby increasing susceptibility to metabolic diseases. The disruption of intracellular insulin signaling, which is characterized by redox imbalance, toxicological effects, and proinflammatory activity, facilitates cellular adaptation to stress. However, this adaptive response can aberrantly induce a dysfunctional feedback loop characterized by diminished cellular insulin responsiveness, a prevalent feature of metabolic disorders. Despite significant advancements in the scientific understanding of EDPs, substantial knowledge gaps and uncertainties persist, impeding progress toward improved health outcomes. This review highlights current findings on the metabolic toxicity of pesticides in the context of obesity and diabetes, concentrating on crucial signaling pathways and a mechanistic perspective that offers insight into resistance channels as reviewed. These findings enhance our understanding of the potential impacts of EDPs on human health.
S. A. Onikanni, Marjorie Dardis Murucci, Talis Gonçalves da Costa et al.· Journal of Molecular Endocri...· 0 citations
Human fertility is declining across industrialised populations, while the incidence of hormone-dependent reproductive cancers rises. Endocrine-disrupting chemicals (EDCs) and structurally related emerging pollutants are implicated in both. These two outcomes are generally reviewed as separate studies. This review argues that they are two latencies of a single molecular toxicology. The compounds concerned are structurally diverse: phthalates, bisphenols, per- and polyfluoroalkyl substances (PFASs), pesticides, polychlorinated biphenyls (PCBs) and dioxins, brominated and organophosphate flame retardants, pharmaceuticals and personal-care products (PPCPs), and micro- and nanoplastics. They nonetheless converge on a limited repertoire of molecular lesions. These include the disruption of hypothalamic–pituitary–gonadal (HPG) signalling through kisspeptin/GnRH and gonadotropin gene expression and interference at nuclear and membrane hormone receptors (ERα/β, AR, GPER, thyroid receptors, AhR, PPARγ). They also include the inhibition of steroidogenesis at StAR and the CYP11A1–CYP17A1–CYP19A1/3β-HSD/17β-HSD cascade and reactive-oxygen-species generation with mitochondrial dysfunction and Keap1–Nrf2 disruption. Epigenetic reprogramming through DNA methylation, histone modification and non-coding RNAs, together with crosstalk with metabolic and immune signalling, completes the set. These lesions produce measurable cytotoxic and genotoxic damage to gametes and the early embryo: sperm DNA fragmentation and 8-oxo-dG accumulation, blood–testis-barrier breakdown, oocyte meiotic-spindle defects, and granulosa-cell apoptosis and pyroptosis. The same receptor, oxidative and genotoxic hubs drive hormone-dependent reproductive carcinogenesis over longer latencies. The review makes three contributions. First, it traces these shared hubs continuously from fertility impairment to malignancy rather than treating them as separate fields. Second, it grades the certainty of the human evidence class by class, so that robust associations can be distinguished from provisional ones. Third, it integrates pseudo-persistent pollutants alongside the classical persistent compounds. These are micro- and nanoplastics, which act as both toxicants and vectors for adsorbed co-contaminants, and pharmaceutical and personal-care residues sustained by continuous wastewater input. Their inclusion demonstrates that chronic low-dose exposure does not require chemical persistence. We conclude with mitigation strategies and an explicit account of what the current evidence base cannot yet support.
Z. El Beaino, J. Ayoubi, Samir Hamamah· International Journal of Mol...· 0 citations
Hormones are key biomolecules that play a crucial role in maintaining the health of individuals.
Endocrine-disrupting compounds (EDCs) are widely distributed environmental contaminants
that interfere with hormonal activities, affecting growth, development, and overall health. Exposure
to EDCs is linked with metabolic disorders, reproductive disorders, neurological disorders,
and cancer. This review examines the properties of EDCs, their interactions with receptors, the
mechanism of action, and their adverse health effects. It highlights strategies to reduce exposure to
EDCs. EDCs are present in various materials of daily life, including plastic bottles, toys, detergents,
metallic food cans, cosmetics, flame retardants, medical devices, and pesticides. Some notable examples
of EDCs are bisphenol A, polychlorinated biphenyls, phthalates, chlorpyrifos, and DDT,
which interfere with hormonal regulation and may also undergo bioaccumulation in the tissues. Exposure
to EDCs primarily occurs through the consumption of contaminated products, inhalation,
and skin contact. Recent studies have revealed that the functions of androgen, estrogen, and thyroid
hormones are commonly affected. Key mechanisms include interaction with receptors (mainly nuclear
receptors) and interference with signalling pathways. It is also suggested that some endocrine
disruptors may cause epigenetic changes and oxidative stress. Nowadays, EDCs are becoming a
growing threat to public health, underscoring the need for enhanced public health initiatives, comprehensive
analysis of long-term health impacts, and globally harmonized emission thresholds to
control the release of EDCs into the environment. Additionally, as these compounds are present in
the environment at low concentrations, highly sensitive analytical techniques are required for their
analysis. Several conventional and advanced analytical techniques (GC-MS, HPLC, LC-MS/MS,
electrochemical sensor, optical biosensor, gold nanoparticle-based detection, carbon nanotubes,
quantum dots) have been used to identify different EDCs from the environmental matrices. Despite
the promising analytical techniques, structural diversity, high mobility, and trace complexity in environmental
matrices make it challenging to identify these compounds in the environment. Additionally,
continued research is required to enhance the understanding of the mechanisms of action of
EDCs and to develop effective mitigation strategies.
Punit Kumar, K. Dubey, Ankush Yadav· Current Chemical Biology· 0 citations
The escalating prevalence of infertility globally is increasingly linked to environmental hormone exposure, particularly Endocrine Disrupting Chemicals (EDCs) such as phthalates, bisphenol A (BPA), pesticides, and industrial pollutants. These ubiquitous contaminants, permeating ecosystems through air, water, food chains, and commercial goods, interfere with hormonal regulation via multifactorial mechanisms: receptor agonism/antagonism, hypothalamic-pituitary-gonadal axis dysregulation, oxidative stress induction, and DNA methylation alterations. EDCs impair gamete quality and elevate congenital reproductive risks in both sexes. EDCs alter hormonal balance, reduce fertility, and induce germline epigenetic changes, potentially causing transgenerational reproductive harm. Critical exposure periods, embryonic development, adolescence, and adulthood, exacerbate risks, with transgenerational epigenetic effects raising concerns for offspring health. High-risk populations, including industrial workers and agricultural laborers, face disproportionate exposure. Clinical interventions like hormone replacement therapy and assisted reproductive technologies offer limited solutions, underscoring the need for preventive strategies. Future research must address combined effects of multi-chemical exposures, long-term low-dose impacts, and epigenetic inheritance. Public health policies should prioritize stricter regulation of EDCs, enhanced environmental monitoring, and public education to mitigate exposure. Individualized health management, including dietary adjustments and reduced plastic use, is crucial. Resolving this public health challenge requires synergistic efforts across toxicogenomics, clinical, and environmental policymaking to ensure sustainable reproductive health preservation.
Wen-Biao Zhou, Chen-Wei Xu, Cheng-Niu Wang et al.· Journal of Endocrinology· 0 citations
This critical narrative review integrates evidence on major environmental genotoxin classes, exposure routes, molecular mechanisms, human biomonitoring, disease associations and risk-assessment practice for well-established and less mature evidence domains.
Omoighele F. Akhigbe, O. Abutu, N. Y. Wike et al.· Asian Journal of Research in...· 0 citations
In the latter half of the 20th century, humans have produced various synthetic chemicals, several of which had serious adverse effects on ecosystems and human health. Colborn et al. noticed that some chemicals disrupt the hormonal system of living organisms. They named these chemicals endocrine-disrupting chemicals (EDCs) and published the book Our Stolen Future. In classical toxicology, toxins directly act on cellular components, such as proteins, DNA, and cell membranes; cause damage and exhibit toxicity; and demonstrate a linear dose-response relationship, thus allowing safe thresholds. EDCs transmit abnormal signals through receptors, thus causing errors in the timing, type, and quantity of gene expression, which lead to adverse effects. Through the hormonal signaling system, EDCs can exhibit hormone-disrupting effects even at low doses, thus making it difficult to establish clear thresholds. EDCs have been reported to cause adverse effects by disrupting the estrogenic, androgenic, thyroid, and other signaling systems. Therefore, EDCs affect not only the endocrine system but also the reproductive, nervous, and immune systems. Owing to the wide-ranging effects of EDCs, there is no standardized definition of EDCs, and further research is needed to scientifically clarify EDCs. However, there are accumulating reports on the health hazards to humans caused by EDCs. Considering the precautionary approach, regulations regarding EDCs need to be reevaluated at both the national and international levels. This review introduces and discusses recent research and public initiatives related to EDCs. Can "our stolen future" be regained?
