Endocrine disruptor chemicals exposure and female fertility declining: from pathophysiology to epigenetic risks

Abstract

Over the last decades, human infertility has become a major concern in public health, with severe societal and health consequences. Growing evidence shows that endocrine disruptors chemicals (EDCs) have been considered as risk factors of infertility. Their presence in our everyday life has become ubiquitous because of their universal use in food and beverage containers, personal care products, cosmetics, phytosanitary products. Exposure to these products has an impact on human reproductive health. Recent studies suggest that women are more exposed to EDCs than men due to higher chemical products use. The aim of this review is to understand the possible link between reproductive disorders and EDCs such as phthalates, bisphenol, dioxins, and pesticides. In women, the loss of endocrine balance leads to altered oocyte maturation, competency, anovulation and uterine disorders, endometriosis, premature ovarian insufficiency (POI) or embryonic defect and decreases the in vitro fertilization outcomes. In this review, we consider EDCs effects on the women's reproductive system, embryogenesis, with a focus on associated reproductive pathologies.

Keywords: endocrine disrupting chemicals; endometriosis; epigenetic; female fertility; female reproductive disorder; infertility; pesticides.

Figure 1

Various groups of endocrine-disrupting chemicals present in daily life. Adapted from Yan et al. (25).

Figure 2

Suggested mechanisms of Bisphenol A impairing decidualization. Exposure to BPA leads to downregulation of steroidogenic acute regulatory protein (StAR) and cP450 expression in theca and granulosa cells. This downregulation hinders the transport of cholesterol into the mitochondria for conversion into pregnenolone, thereby disrupting the E2 biosynthetic pathway and impairing the normal function of the HPG axis.

Figure 3

Suggested mechanisms of Bisphenol A impairing decidualization. Exposure to low doses of BPA leads to an upregulation of estrogen (ER) and progesterone (PR) receptors. This reduces the levels and activities of antioxidant enzymes (superoxide dismutase [SOD], glutathione peroxidase [GPx], heme oxygenase [HO], and catalase [CAT]), and thus increasing ROS level leading to an impaired decidualization. Exposure to high level of BPA downregulates the ER and PR, increase the expression of early growth response-1 (EGR1) and reduce the expression of glucocorticoid-induced kinase-1 (SGK1), resulting in elevated ROS levels, which in turn impair decidualization. Adapted from Nelson et al. (64).

Figure 4

Impact of EDCs exposure on the reproductive system and fetal development associated with impaired female fertility.