Different types of bisphenols alter ovarian steroidogenesis: Special attention to BPA

Endocrine disruptors such as bisphenol A (BPA) and some of its analogues, including BPS, BPAF, and BPE, are used extensively in the manufacture of plastics. These synthetic chemicals could seriously alter the functionality of the female reproductive system. Although the number of studies conducted on other types of bisphenols is smaller than the number of studies on BPA, the purpose of this review study was to evaluate the effects of bisphenol compounds, particularly BPA, on hormone production and on genes involved in ovarian steroidogenesis in both in vitro (human and animal cell lines) and in vivo (animal models) studies. The current data show that exposure to bisphenol compounds has adverse effects on ovarian steroidogenesis. For example, BPA, BPS, and BPAF can alter the normal function of the hypothalamic-pituitary-gonadal (HPG) axis by targeting kisspeptin neurons involved in steroid feedback signals to gonadotropin-releasing hormone (GnRH) cells, resulting in abnormal pro-duction of LH and FSH. Exposure to BPA, BPS, BPF, and BPB had adverse effects on the release of some hormones, namely 17-8-estradiol (E2), progesterone (P4), and testosterone (T). BPA, BPE, BPS, BPF, and BPAF are also capable of negatively altering the transcription of a number of genes involved in ovarian steroidogenesis, such as the steroidogenic acute regulatory protein (StAR, involved in the transfer of cholesterol from the outer to the inner mitochondrial membrane, where the steroidogenesis process begins), cytochrome P450 family 17 subfamily A member 1 (Cyp17a1, which is involved in the biosynthesis of androgens such as testosterone), 3 beta-hydroxysteroid dehydrogenase enzyme (38-HSD, involved in the biosynthesis of P4), and cyto-chrome P450 family 19 subfamily A member 1 (Cyp19a1, involved in the biosynthesis of E2). Exposure to BPA, BPB, BPF, and BPS at prenatal or prepubertal stages could decrease the number of antral follicles by activating apoptosis and autophagy pathways, resulting in decreased pro-duction of E2 and P4 by granulosa cells (GCs) and theca cells (TCs), respectively. BPA and BPS impair ovarian steroidogenesis by reducing the function of some important cell receptors such as estrogens (ERs, including ER & alpha; and ER8), progesterone (PgR), the orphan estrogen receptor gamma (ERR & gamma;), the androgen receptor (AR), the G protein-coupled estrogen receptor (GPER), the FSHR (follicle-stimulating hormone receptor), and the LHCGR (luteinizing hormone/choriogo-nadotropin receptor). In animal models, the effects of bisphenol compounds depend on the type of animals, their age, and the duration and dose of bisphenols, while in cell line studies the duration and doses of bisphenols are the matter.

Automated summary

Endocrine disruptors such as BPA can severely affect the functionality of the female reproductive system by altering hormone production and genes involved in ovarian steroidogenesis. Exposure to bisphenol compounds can disrupt the normal function of the HPG axis, leading to abnormal production of LH and FSH. These compounds also negatively affect the release of hormones such as E2, P4, and T, and alter the transcription of genes involved in ovarian steroidogenesis.