Environmental pollutants as endocrine disruptors

INTRODUCTION

The endocrine system is crucial for regulating hormones, which are involved in numerous physiological processes such as growth, metabolism, reproduction, and mood regulation. Environmental pollutants, particularly those released from industrial, agricultural, and urban sources, have been identified as endocrine disruptors. These substances mimic, block, or alter the normal functioning of hormones, leading to adverse health effects in both humans and wildlife. This review aims to summarize the current understanding of how environmental pollutants affect the endocrine system and the resulting health implications.

“Any agent that interferes with the synthesis, secretion, transport, binding, or elimination of natural hormones in the body that are responsible for the maintenance of homeostasis, reproduction, development, and/or behavior” is what the U.S. Environmental Protection Agency defines as an endocrine-disrupting compound.^[1] To put it simply, endocrine disruptors are substances or combinations of substances that interfere with the normal action of hormones. Because of the high toxicity and carcinogenic nature of endocrine-disrupting chemicals (EDCs), prolonged exposure to these can lead to long-term health impacts. Owing to the traits of being persistent and bioaccumulative, both humans and the environment are currently confronted with a catastrophe that has not yet materialized.^[2] Figures 1 and 2 categorize EDCs based on their type and source, respectively. Figure 1 specifies EDCs by type, distinguishing between naturally occurring and synthetic compounds, with examples^[3], and Figure 2 highlights their typical applications or sources.^[4] Figure 3 highlights various EDCs – including bisphenol A (BPA), phthalates, lead, and atrazine – commonly found in everyday items such as food products, personal care items, electronics, textiles, medicines, and pesticides.^[5,6]

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Figure 1:

Classification of endocrine-disrupting chemicals by type. PCB: Polychlorinated biphenyl, PBB: Polybrominated biphenyl, DDT: Dichlorodiphenyltrichloroethane

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Figure 2:

Classifications of endocrine-disrupting chemicals by source. PAH: Polycyclic aromatic hydrocarbons.

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Figure 3:

Common endocrine-disrupting chemicals and their uses. DDT: Dichlorodiphenyltrichloroethane, BPA: Bisphenol A. PCB: Polychlorinated biphenyl.

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BRIEF INTRODUCTION TO THE ENDOCRINE SYSTEM AND ITS ROLE

The endocrine system, a network of glands and organs distributed throughout the body, plays a crucial role in regulating various physiological processes through the production and secretion of hormones directly into the bloodstream. These hormones, acting as chemical messengers, travel through the circulatory system to reach specific target organs and tissues, where they influence a wide array of bodily functions. While endocrine signaling is slower than the nervous system’s rapid electrical communication, its effects are far-reaching and enduring, significantly impacting development, metabolism, mood, reproduction, and the maintenance of homeostasis. Central to this system are glands, which serve as the primary producers and secretors of hormones, releasing them directly into the bloodstream to orchestrate vital activities such as immune regulation, growth, metabolism, reproduction, and electrolyte balance. Key glands include the pituitary gland, often called the “master gland” for its regulatory control over other endocrine glands and critical processes; the thyroid gland, which governs metabolic rate and energy balance; and the adrenal glands, responsible for hormone production that aids stress response and maintains electrolyte and fluid homeostasis. Alongside other important glands such as the pancreas, ovaries, and testes, these organs form a complex hormonal network essential for sustaining the body’s internal equilibrium and overall health. Disruption of this finely tuned hormonal network by external compounds, such as EDCs, can lead to significant physiological imbalances, and understanding how these chemicals interfere with hormone function at the molecular level is essential to assessing their impact on human and environmental health.

HORMONAL FEEDBACK LOOPS

To maintain hormonal balance, the endocrine system primarily relies on feedback mechanisms, with negative feedback being the most common. In this process, elevated hormone levels trigger a response that suppresses further secretion. For example, when blood glucose rises, the pancreas releases insulin to promote glucose uptake; as glucose levels return to normal, insulin release is reduced. In contrast, positive feedback is less common and involves the amplification of hormone release. A classic example occurs during childbirth: Oxytocin-induced uterine contractions stimulate further oxytocin release, continuing until delivery.

While these feedback systems are vital for physiological stability, growing scientific concern has emerged over environmental pollutants that act as EDCs – substances capable of mimicking or interfering with natural hormones. Recent research has highlighted the broad impact of EDCs on hormonal regulation and development. A 2024 study by the National Institute of Environmental Health Sciences identified musk ambrette, a fragrance in personal care products, as an EDC that may prematurely activate the reproductive axis in children by stimulating receptors such as gonadotropin-releasing hormone receptor and KISS1R, potentially contributing to early puberty in girls.^[7] Similarly, a 2024 study from the Barcelona Institute for Global Health found that prenatal exposure to EDC mixtures was associated with poorer metabolic health in children, increasing the risk of metabolic syndrome later in life. These findings emphasize the urgent need for stronger public health measures to reduce EDC exposure, especially during critical developmental periods. To understand the mechanisms behind these effects, it is essential to examine how EDCs disrupt hormone signaling at the molecular level.

WHY IT’S A GROWING CONCERN

The growing concern surrounding EDCs is amplified by their ubiquity, as these substances are not confined but rather are widespread, permeating various products we use daily and existing pervasively within the environment itself. Adding to this concern is their persistence; many EDCs exhibit a resistance to natural degradation processes, leading to their accumulation not only within diverse ecosystems but also within the bodies of living organisms over extended periods. Furthermore, research has highlighted the potential for low-dose effects, indicating that even exposures to relatively small amounts of these chemicals, particularly during critical and sensitive developmental windows such as the in utero period, can precipitate long-term and potentially adverse health consequences. The environmental ramifications of EDCs extend to the contamination of soil and waterways, subsequently impacting wildlife populations. Within aquatic environments, fish and amphibian species may exhibit noticeable signs of feminization or various reproductive abnormalities as a consequence of EDC exposure. Similarly, terrestrial wildlife, including birds and mammals, can experience disruptions to their natural breeding cycles and exhibit altered behavioral patterns due to the presence of these endocrine-interfering substances in their environment.

Endocrine disruptors act through various mechanisms that interfere with the normal functioning of hormones and their receptors. These mechanisms can be divided into several key categories. Some pollutants resemble naturally occurring hormones, such as estrogen, and can bind to hormone receptors, triggering similar biological responses.

For example, the synthetic estrogen-like compound BPA can bind to estrogen receptors and disrupt the endocrine system. Certain pollutants have structures similar to natural hormones like estradiol, allowing them to bind to hormone receptors and trigger (or block) hormonal responses like BPA mimics estrogen.^[8-10] BPA can bind to estrogen receptors α and β, causing similar gene activation as estradiol.^[11] Some pollutants can activate hormone receptor (agonists) and also can block receptor and prevent natural hormones from binding (antagonists) like dichlorodiphenyltrichloroethane (DDT) and its metabolite dichlorodiphenyldichlororthylene (DDE). DDE is an androgen receptor antagonist, affecting male reproductive development.^[12] Some EDCs disrupt enzymes responsible for hormone production or degradation, altering hormonal balance. For example, polychlorinated biphenyls (PCBs) affect thyroid hormone levels by increasing their clearance from the blood.^[13]

A few pollutants bind to hormone-binding proteins like thyroxine-binding globulin, reducing the availability of active hormones. EDCs can alter deoxyribonucleic acid (DNA) methylation and histone modification, leading to long-term or trans generational effect.^[14] Vinclozolin, a fungicide, causes epigenetic changes in sperm, affecting several generations.^[15] Natural hormones cannot bind and have their desired effects when some contaminants block hormone receptors. Dioxins, for instance, have the ability to bind to the aryl hydrocarbon receptor and interfere with regular signaling pathways.^[16] Environmental pollutants can also interfere with the synthesis, metabolism, or elimination of hormones, leading to imbalances. Numerous pathways expose humans to a wide variety of substances. In the course of daily life, environmental contaminants are typically transferred to the human body unconsciously. Ingestion is the primary way that humans are exposed to EDCs, with inhalation and skin absorption also playing a role.

ENVIRONMENT POLLUTANTS: ENDOCRINE DISRUPTORS

HEALTH IMPACTS OF ENDOCRINE DISRUPTION

The effects of endocrine disruption are varied and influenced by factors such as the type of chemical involved, the dose, duration, and, importantly, the timing of exposure. Health outcomes associated with EDCs span multiple systems, including the neurodevelopmental, metabolic, and reproductive domains. Exposure during sensitive developmental windows – particularly prenatal and early postnatal periods – has raised concerns about links to cognitive and behavioral disorders. Although conditions such as attention-deficit hyperactivity disorder and autism spectrum disorders (ASD) are complex and multifactorial, involving genetic, environmental, and developmental influences, some studies suggest that certain EDCs may contribute to neurodevelopmental risk by disrupting hormone-regulated brain development.^[19,20] EDCs are also strongly implicated in metabolic disturbances, contributing to obesity and type 2 diabetes by interfering with insulin signaling and lipid metabolism.^[21,22] In the reproductive system, these chemicals can cause developmental and functional abnormalities, including altered sexual differentiation, reduced fertility, and hormonal imbalances.^[3,23] Substances such as BPA, phthalates, and specific pesticides have been closely linked to such reproductive outcomes. Given the breadth of potential health impacts and the ongoing exposure to these pollutants, further research and stronger regulatory frameworks are essential to better understand risks and reduce harm, particularly during vulnerable stages of human development.

REPRODUCTIVE HEALTH

EDCs, such as BPA, phthalates, and perfluoroalkyl substances (PFASs), have been extensively studied for their adverse effects on human reproductive health. A growing body of evidence has linked exposure to these compounds with impaired fertility in both males and females. In males, BPA exposure has been associated with reduced sperm count, abnormal sperm morphology, decreased motility, increased DNA fragmentation, hormonal dysregulation, and testicular atrophy. Similarly, phthalate exposure has been correlated with compromised semen quality and disrupted androgen synthesis.^[24] PFASs have also been shown to impair male reproductive function by disrupting hormonal balance, damaging seminiferous tubules, and reducing sperm quality and count.^[25] These effects are primarily attributed to the interference of EDCs with the hypothalamic–pituitary– gonadal (HPG) axis and the modulation of key reproductive hormones, including testosterone and follicle-stimulating hormone.

In females, BPA and phthalates disrupt hormonal homeostasis essential for ovulatory function, leading to menstrual irregularities, reduced ovarian reserve, and increased risks of infertility. BPA exposure, in particular, has been implicated in the etiology of polycystic ovary syndrome and endometriosis. Phthalates may also impair ovarian folliculogenesis and alter uterine receptivity, contributing to reproductive disorders.^[26] Furthermore, both BPA and phthalates are capable of crossing the placental barrier, raising concerns regarding their impact during critical windows of fetal development. Prenatal exposure to these chemicals has been linked to structural malformations of the reproductive tract, as well as long-term neurodevelopmental impairments in offspring. Another study highlighted EDCs, oxidative stress, inflammation, and altered intra-ovarian signaling collectively impair ovarian function and female reproductive health.^[27]

Collectively, these findings underscore the need for robust regulatory frameworks aimed at limiting human exposure to EDCs, particularly during sensitive developmental stages.^[28] Continued research is essential to further elucidate the mechanisms of EDC action and to inform public health interventions that mitigate their reproductive and developmental consequences.

REGULATORY AND MITIGATION EFFORTS

In response to growing concerns over the health and environmental impacts of EDCs, many countries have implemented regulations aimed at limiting the use of these harmful substances. These regulations seek to reduce human and environmental exposure to pollutants, especially those that are persistent and bioaccumulative. Key international frameworks, such as the Stockholm Convention, address POPs such as PCBs and DDT,^[36] while the European Union’s Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH) regulation focuses on managing chemical risks and ensuring safer use of chemicals.^[37]

Despite these efforts, significant challenges remain. Many EDCs persist in the environment for extended periods, making remediation difficult. In addition, the current regulatory testing frameworks often lack comprehensive methods to fully assess endocrine-disrupting potential. Specifically, there is a critical need for more advanced in vitro assays, such as receptor-binding and cell-based reporter gene assays, as well as high-throughput screening techniques that can evaluate multiple hormonal pathways simultaneously. These methods would complement traditional in vivo animal testing, providing faster and more mechanistic insights into how EDCs affect endocrine function.

Moreover, a notable gap exists between scientific knowledge and regulatory implementation, particularly in developing countries. For example, in parts of Southeast Asia, where pesticide use remains high and regulatory enforcement is limited, exposure to banned or unregulated EDCs continues unabated, contributing to adverse health outcomes without adequate policy response.^[38] This illustrates the urgent need for capacity building, improved infrastructure, and international collaboration to support these regions in adopting and enforcing effective regulations.

Addressing these challenges will require strengthened global cooperation, the integration of cutting-edge testing methods into regulatory frameworks, and targeted efforts to close policy gaps, especially in vulnerable and resource-limited regions. Only through such comprehensive action can the widespread risks posed by EDCs to human health and ecosystems be effectively mitigated.

CONCLUSION

Endocrine-disrupting environmental pollutants present considerable risks to human health and ecosystems by interfering with hormonal regulation and impacting reproductive, metabolic, and developmental processes. While significant advances have been made in elucidating their mechanisms of action, substantial challenges persist in effectively regulating and mitigating exposure. Ongoing research is imperative to refine detection techniques – particularly for low-dose exposures and complex biochemical pathways – and to understand the combined and synergistic effects of multiple chemicals. Moreover, closing the gap between scientific evidence and regulatory implementation, especially in resource-limited regions, remains essential. Strengthening international collaboration through frameworks such as the Stockholm Convention and the European Union’s REACH regulation, alongside evidence-based policy-making and targeted preventive measures, is critical to safeguarding public health, preserving ecosystems, and protecting future generations from the adverse effects of endocrine disruptors.