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Review
. 2022 Dec;89(12):608-631.
doi: 10.1002/mrd.23652. Epub 2022 Nov 19.

The effects of endocrine-disrupting chemicals on ovarian- and ovulation-related fertility outcomes

Katie L Land  1 , Frances G Miller  1 , Ava C Fugate  1 , Patrick R Hannon  1
Affiliations
Review

The effects of endocrine-disrupting chemicals on ovarian- and ovulation-related fertility outcomes

Katie L Land et al. Mol Reprod Dev. 2022 Dec.

Abstract

Exposure to endocrine-disrupting chemicals (EDCs) is unavoidable, which represents a public health concern given the ability of EDCs to target the ovary. However, there is a large gap in the knowledge about the impact of EDCs on ovarian function, including the process of ovulation. Defects in ovulation are the leading cause of infertility in women, and EDC exposures are contributing to the prevalence of infertility. Thus, investigating the effects of EDCs on the ovary and ovulation is an emerging area for research and is the focus of this review. The effects of EDCs on gametogenesis, uterine function, embryonic development, and other aspects of fertility are not addressed to focus on ovarian- and ovulation-related fertility issues. Herein, findings from epidemiological and basic science studies are summarized for several EDCs, including phthalates, bisphenols, per- and poly-fluoroalkyl substances, flame retardants, parabens, and triclosan. Epidemiological literature suggests that exposure is associated with impaired fecundity and in vitro fertilization outcomes (decreased egg yield, pregnancies, and births), while basic science literature reports altered ovarian follicle and corpora lutea numbers, altered hormone levels, and impaired ovulatory processes. Future directions include identification of the mechanisms by which EDCs disrupt ovulation leading to infertility, especially in women.

Keywords: endocrine-disrupting chemicals; fertility; ovary; ovulation; reproduction.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Regulation of preovulatory follicle development, ovulation, and corpus luteum (CL) formation. Boxes 1: At the initiation of the menstrual cycle, gonadotropin‐releasing hormone (GnRH) from the hypothalamus stimulates follicle‐stimulating hormone (FSH) secretion from the anterior pituitary. FSH acts on early antral follicles. The oocyte is depicted in yellow, granulosa cells in red, theca cells in gray, and follicular fluid in blue. Box 2: FSH action causes the development of a single, dominant preovulatory follicle. Box 3: The preovulatory follicle produces abundant levels of estradiol (E2), which causes positive feedback to the hypothalamus. Boxes 4: This positive feedback increases GnRH pulsatility, which initiates the luteinizing hormone (LH) surge. LH binds to LH receptors on granulosa cells of the follicle. Box 5: LH action induces the ovulatory cascade by increasing ovulatory mediators and stimulating several ovarian processes (text box below ovulation; ECM, extracellular matrix), culminating in egg release. The released egg is contained in an expanded matrix with the cumulus cells and has undergone meiotic maturation to metaphase II as depicted by germinal vesicle breakdown and the green extruded polar body. Box 6: Following release of the egg, the remnant follicular cells are now differentiated into luteal cells of the CL that predominantly produce progesterone (P4). P4 from the CL, as well as E2, are required for the initiation and maintenance of pregnancy.
Figure 2
Figure 2
Overview of the effects of EDCs on ovarian‐ and ovulation‐related fertility outcomes. CL, corpora lutea; COC, cumulus oocyte complex; EDCs, endocrine‐disrupting chemicals; E2, estradiol; FRs, flame retardants; FSH, follicle‐stimulating hormone; GnRH, gonadotropin‐releasing hormone; LH, luteinizing hormone; PFAS, per‐ and poly‐fluoroalkyl substances; P4, progesterone.
See this image and copyright information in PMC

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