Environmental toxin exposure in polycystic ovary syndrome women and possible ovarian neoplastic repercussion

Abstract

Over the last two decades, increasing attention has been paid to environmental toxins and their effects on the female reproductive system. Endocrine disrupting chemicals (EDCs) are exogenous substances or mixtures that can mimic the action of steroid hormones and interfere with their metabolism. Advanced glycation end products (AGEs) are proinflammatory molecules that can interact with cell surface receptors and mediate the triggering of proinflammatory pathways and oxidative stress. The purpose of this review is to explore the effects of environmental toxins exposure in the pathogenesis of both polycystic ovary syndrome (PCOS) and OC (ovarian cancer), considered separately, and also to evaluate possible neoplastic ovarian repercussion after exposure in patients diagnosed with PCOS. Materials and methods:We searched PubMed for articles published in the English language with the use of the following MeSH search terms: "Polycystic Ovary Syndrome" and "Ovarian Cancer" combined with "endocrine disruptors". Titles and abstracts were examined and full articles that met the selection criteria were retrieved. A manual search of review articles and cross-references completed the search.Results: Extensive data from different studies collected in recent years concerning the effects of EDCs/AGEs exposure have confirmed their role in the pathophysiology of both PCOS and OC. They favour PCOS/OC development through different mechanisms that finally lead to hormonal and metabolic disruption and epigenetic modifications.Conclusions: Environmental toxin exposure in PCOS women could favour neoplastic transformation by exacerbating and potentiating some PCOS features. Further research, although difficult, is needed in order to prevent further diffusion of these substances in the environment, or at least to provide adequate information to the population considered at risk.

Polycystic Ovary Syndrome: A Comprehensive Review of Pathogenesis, Management, and Drug Repurposing

“…As an example, bisphenol A (BPA) BPA is a synthetic compound used in polycarbonate plastics, epoxy resins [ 25 , 28 ], dental filling, food and drink packages [ 25 ], baby bottles, and polyvinyl chloride (PVC) [ 28 ], which affects metabolism through different pathways. BPA directly affects oogenesis [ 29 ] by interacting with estrogen receptor (ER) α and β, non-classical membrane ER, and G-protein coupled receptor 30 (GPCR30) [ 21 , 28 , 29 ]. It also triggers androgen secretion and restrains testosterone catabolism in theca cells [ 21 , 29 ].…”

“…BPA directly affects oogenesis [ 29 ] by interacting with estrogen receptor (ER) α and β, non-classical membrane ER, and G-protein coupled receptor 30 (GPCR30) [ 21 , 28 , 29 ]. It also triggers androgen secretion and restrains testosterone catabolism in theca cells [ 21 , 29 ].…”

“…Another effect of BPA on interstitial theca cells is the overproduction of androgens by dysregulation of 17β-hydroxylase (P450c17) [ 28 , 30 ], cholesterol side-chain cleavage enzyme (P450scc), and steroidogenic acute regulatory protein [ 30 ]. BPA’s influence on granulosa cells refers to reducing the expression of aromatase enzyme and production of estrogen [ 21 , 29 ]. Lastly, it disturbs the intrafollicular environment and damages the oocyte development and maturation [ 21 , 29 ].…”

“…BPA’s influence on granulosa cells refers to reducing the expression of aromatase enzyme and production of estrogen [ 21 , 29 ]. Lastly, it disturbs the intrafollicular environment and damages the oocyte development and maturation [ 21 , 29 ]. BPA’s indirect effect on HA involves downregulation of testosterone 2a-hydroxylase and testosterone 6b-hydroxylase enzymes in liver level, and thus a higher concentration of testosterone [ 30 , 31 ].…”

Epigenetic Modifications Associated with Exposure to Endocrine Disrupting Chemicals in Patients with Gestational Diabetes Mellitus

“…Daily, constant exposure to EDC mixtures in concentrations even below the established threshold tolerated by the human body for individual substances can significantly increase the risk of developing hormonal and metabolic disorders, such as obesity, diabetes, polycystic ovary syndrome, and cardiovascular disease, as well as malformations, infertility, and hormone-dependent cancers in both women and men [ 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 ].…”