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Ahn, C.; Jeung, E. Brief Properties of Endocrine-Disrupting Chemicals. Encyclopedia. Available online: https://encyclopedia.pub/entry/42212 (accessed on 20 July 2025).
Ahn C, Jeung E. Brief Properties of Endocrine-Disrupting Chemicals. Encyclopedia. Available at: https://encyclopedia.pub/entry/42212. Accessed July 20, 2025.
Ahn, Changhwan, Eui-Bae Jeung. "Brief Properties of Endocrine-Disrupting Chemicals" Encyclopedia, https://encyclopedia.pub/entry/42212 (accessed July 20, 2025).
Ahn, C., & Jeung, E. (2023, March 15). Brief Properties of Endocrine-Disrupting Chemicals. In Encyclopedia. https://encyclopedia.pub/entry/42212
Ahn, Changhwan and Eui-Bae Jeung. "Brief Properties of Endocrine-Disrupting Chemicals." Encyclopedia. Web. 15 March, 2023.
Brief Properties of Endocrine-Disrupting Chemicals
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This entry is adapted from the peer-reviewed paper 10.3390/ijms24065342

Endocrine-disrupting chemicals (EDCs) have significant impacts on biological systems, and have been shown to interfere with physiological systems, especially by disrupting the hormone balance.

endocrine system endocrine disrupting chemical endocrine-related diseases

1. Introduction

Various endocrine-disrupting chemicals (EDCs) are found in the environment. These EDCs affect hormone synthesis or receptor binding by altering the hormone homeostasis of the endocrine system [1]. EDCs can cause reproductive, developmental, and sexual behavior dysfunctions, leading to detrimental results in animals and human beings. Most EDCs from natural or synthetic sources have structures similar to those of endogenous steroid hormones, including estradiol(E2) or androgen. Hence, they tend to interfere with the actions of steroid hormones by binding to the corresponding hormone receptors [2].
Endocrine disruption by EDCs can occur by altering the normal hormone levels, inhibiting or stimulating the production of hormones, or changing the way hormones travel throughout the body, thus affecting the functions of these hormones [3]. EDCs were initially thought to exert their actions solely through nuclear hormone receptors (NRs), including estrogen receptors [ERs, i.e., Bisphenol A(BPA) and dioxins] [4], androgen receptors (ARs, i.e., pesticides, phthalates, plasticizers, polyhalogenated compounds), progesterone receptors (PR), thyroid receptors [TRs, i.e., BPA, dioxins, perchlorates, furans], and retinoid receptors (i.e., Organotins, BPA) [3][5]. On the other hand, recent evidence has shown that the mechanisms through which EDCs act are much broader than originally recognized [4]. Indeed, studies have shown that in addition to altering nuclear receptor signaling, EDCs can act through the nonsteroid receptors, transcriptional coactivators, enzymatic pathways involved in steroid biosynthesis and metabolism, and numerous other mechanisms that converge upon endocrine and reproductive systems [5][6]. Other less well-known mechanisms of action of EDCs include the direct effects on genes [7]. Several important principles demonstrate how environmental exposures increase the risks of adult disease [8]. First, chemical exposure can have both tissue-specific and time-specific consequences on growth and development. Second, the pathophysiology may be manifested in a disease that might otherwise not have occurred and disease progression may have variable latent periods. Finally, the effects of environmental chemical exposures can be transgenerational, thereby affecting future generations.
Unlike the traditional mechanism of action of EDCs, recently, EDCs are regarded as a trigger for endoplasmic reticulum stress; however, the basal molecular mechanisms regarding EDCs and the endoplasmic reticulum are still lacking. Nevertheless, there is several evidence that some EDCs may have apoptotic effects on various cells in the body in relation to inducing endoplasmic reticulum stress depending on the concentration of exposure [9][10][11][12][13][14][15]. Endocrine-disrupting chemicals such as bisphenol A, alkylphenols, dioxins, perchlorates, Furans, and pesticides that enter the aquatic ecosystem not only interferes with aquatic organisms but also with terrestrial and aerial animals linked directly or indirectly with water through food chains or other ecological interactions [16]. The presence of chemicals exhibiting endocrine-disrupting properties has significantly increased in the ecosystem [5]. Therefore, there is growing concern about their potential ability to induce/exacerbate diseases in relation to EDCs. Indeed, due to their wide use and direct link to adverse human health concerns, the Endocrine Society published a scientific statement in 2009 indicating that endocrine disruptors pose a “significant concern for public health” [5]. Possible diseases in relation to endocrine-disrupting chemical have been listed.

2. Brief Properties of EDCs

2.1. Complex Mechanisms of EDCs

Some EDCs act via several mechanisms and have mixed steroidal properties. For example, an EDC may have both estrogenic and anti-androgenic or have estrogenic and progesterone properties [5]. Moreover, the metabolite of EDCs could have different actions compared to its original structure. For instance, the estrogen agonist, Dichlorodiphenyltrichloroethane (DDT), is metabolized into the androgen antagonist Dichlorodiphenyldichloroethylene (DDE) [17]. EDCs can also act through genomic and non-genomic mechanisms. Genomic responses are delayed and require several hours to become established [18]. In addition to genetic modulation, non-genomic responses occur rapidly, often within minutes of exposure. EDCs act by modulating the endogenous steroid hormone metabolism, nuclear receptor coactivators (NCOAs), and proteasome-targeted degradation of endogenous hormones. The mechanisms of EDCs involve divergent pathways including estrogenic, androgenic, thyroid, peroxisome proliferator-activated receptor γ (PPARγ), retinoid, and other nuclear receptors. Endocrine-disrupting chemicals are thought to act primarily through NRs including ERs, ARs, PRs, TRs, and others [5]. Thus, endocrine disruptors act via NR, nonnuclear steroid hormone receptors (e.g., membrane ERs), nonsteroid receptors (e.g., neurotransmitter receptors such as the serotonin receptor, dopamine receptor, norepinephrine receptor), orphan receptors [e.g., aryl hydrocarbon receptor (AhR)—an orphan receptor], enzymatic pathways involved in steroid biosynthesis and/or metabolism, and numerous other mechanisms [5].
EDCs such as BPA, zearalenone (Zea), and nonylphenol (NP) also had relatively high binding affinities for G protein-coupled estrogen receptors (GPER) [19][20][21]. GPER-dependent signaling pathway activated by estrogens. Following nontraditional estrogen actions mediated through GPER are a key mechanism to disruption by a variety of environmental estrogens [22]. In contrast, EDCs such as polychlorinated biphenyls (PCBs) and dioxin bind with relatively high affinity to the AhR [23][24]. It regulates the transcription of a large group of dioxin-responsive genes and results in a reduction in cytosolic estrogen levels [25]. EDCs exert their toxic effects by interfering with hormonal production, secretion, and action that affect the growth and development of reproductive tissues [25]. These exogenous chemicals interfere with the binding of hormones to their receptors such as ERs and ARs which can result in an agonistic or antagonistic effect [5]. For example, an organochlorine pesticide (methoxychlor) has been reported to cause estrogenic action by binding to estrogen receptor α (ERα) and estrogen receptor β (ERβ) subtypes [26]. In addition to receptor interference, EDCs can also interfere with enzyme action involved in steroidogenesis. Phthalates and such plasticizers exert anti-androgenic activity by disrupting steroidogenesis in the H295R assay [27]. It has been reported that some EDCs inhibit 5-α reductase that converts testosterone to dihydrotestosterone [28][29]. Thus, EDCs can affect hormone receptor expression. It has been reported that BPA alters the epigenome and causes the malregulation of steroid receptors [30].
Some EDCs such as BPA and alkylphenols exert endoplasmic reticulum (ER) stress. The exact mechanism of how EDCs cause endoplasmic reticulum stress still needs to be studied. On the other hand, endoplasmic reticulum stress markers must be significantly increased in order to indicate EDC exposure. Endoplasmic reticulum stress activates a signaling network called the unfolded protein response (UPR) to restore endoplasmic reticulum homeostasis. However, under prolonged and severe endoplasmic reticulum stress by EDCs, the UPR can become cytotoxic [14][31].

2.2. Transgenerational Effects

Mutations or subtle modifications of gene expression induce the transgenerational effects of EDCs. It is still unclear how EDC exposure during early development leads to phenotypic changes that manifest as diseases much later in life or even in the next generation [32]. On the other hand, increasing evidence suggests a central role for epigenetic mechanisms in the transgenerational effects of EDCs [5]. In recent years, several experimental studies and some evidence from epidemiology have shown that EDCs induce epigenetic changes [33]. Epigenetic modifications are the “heritable and reversible modifications of chromatin, resulting in an adjustment of its activity without changing the underlying DNA sequence, such as histone modification and non-coding RNA” [32]. Epigenetic alterations of the germline can include DNA methylation, histone modifications, and noncoding RNAs [34][35]. Epigenetic alterations can be transmitted through the germline to the unexposed generation to cause effects on subsequent generations and cause transgenerational phenomena [34][35]. By DNA methylation, DNA methyltransferases add a methyl group to the cytosine base, and methylation is usually associated with the repression of transcription. Histone modification involves altering the chromatin structure; it also takes a part in the regulation of gene expression [36]. Lastly, noncoding RNAs are involved in chromatin function and can modulate gene expression with gene silencing. Known EDCs that affect male and female reproduction include phthalates, BPA, pesticides, and environmental contaminants, including polychlorinated biphenyls (PCBs) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) [35][37][38][39][40]. Those EDCs which effects the germline showed negative effects on male and female fertility in a transgenerational manner. In animal studies with females individuals, ancestral (primary) EDC exposure can alter transgenerational litter size and anogenital distance, cause early puberty, disrupt estrous cyclicity, alter follicle numbers, decrease fertility, cause early reproductive aging, increase cysts in ovaries, alter sex steroid hormone levels, and cause adenomyosis. Furthermore, in males, ancestral EDC exposure can alter transgenerational anogenital distance, cause testes disease, cause early puberty, decrease fertility, decrease sperm count and motility, alter sperm morphology, and alter sex steroid hormone levels [35][37][38][39][40][41][42].

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