**Funding**

Furthermore, adiponectin receptors are expressed by oocytes and early embryos of the pig and mouse [81]. In vitro studies report adiponectin to decrease insulin‐induced androgen and

secretion in bovine theca cells. In rat, chicken and human cultured granulosa cells, how‐

ferent species, including humans, indicate that adiponectin can modulate not only granulosa cell steroidogenesis but also the expression of genes involved in ovulation. In the cow, adipo‐ nectin decreases insulin‐induced steroidogenesis and increases IGF‐1–induced proliferation of cultured granulosa cells. Adiponectin does not affect oocyte maturation and embryo devel‐ opment in vitro [82]; however, it stimulates oocyte meiotic maturation and embryo develop‐

The serum adiponectin level is markedly lower in patients with early‐stage ovarian cancer than in healthy women. Adiponectin possesses anti‐tumourigenic properties; it can suppress tumour growth and cell proliferation, arrest cell growth and induce apoptosis. AdipoR1 promotes KGN cell survival, whereas AdipoR2 regulates steroid hormone synthesis by acti‐ vating MAPK ERK1/2 [83]. Furthermore, the AdipoR1 mRNA level was lower in Leghorn chicken cancerous ovaries than in normal ovaries [84], suggesting that adiponectin signalling restricts ovarian cancer progression by suppressing tumour cell proliferation and inducing

Human cancerous ovarian epithelial cell lines (OVCAR‐3, SKOV‐3 and Caov‐3), the cancerous granulosa cell line (COV434) and the non‐cancerous ovarian epithelial cell line (HOSEpiC) express AdipoR1 and AdipoR2, but not adiponectin. Moreover, the AdipoR1 mRNA level is markedly higher in OVCAR‐3, SKOV‐3, Caov‐3 and COV434 cells than in HOSEpiC cells, whereas the AdipoR2 mRNA level is similar among all tested cell lines. BPA does not affect AdipoR1 and AdipoR2 expression (unpublished data), although it decreases the expression and secretion of adiponectin in 3T3‐L1 adipocytes [85]. In cultured porcine ovarian follicles, however, BPA markedly increases the expression and secretion of adiponectin, as well as the expression of its receptors, indicating that this environmental toxicant contributes to ovarian

BPA can alter ovarian function through several mechanisms. In this chapter, we have dis‐ cussed two mechanisms by which BPA alters ovarian function. In the first mechanism, BPA acts directly by reducing oocyte quality after foetal and early postnatal exposure; altering the expression and/or activity of key steroidogenic enzymes required for steroid hormone synthesis; binding to steroid hormone receptors and preventing the binding of endogenous ligands; stimulating ovarian cancer cell proliferation and migration; and inhibiting cell apop‐ tosis. In the second mechanism, BPA acts indirectly by altering the expression of adipokines and adipokine receptors, which exhibit endocrine and autocrine actions in ovarian cells. Further studies are needed to understand the effects of BPA on the ovary and its contribution

to ovarian dysfunction, such as decreased fertility, PCOS and carcinogenesis.

secretion in response to IGF‐1. Several reports in dif‐

and/or E<sup>2</sup>

dysfunction in obesity‐related disorders (unpublished data).

P4

ever, adiponectin increases P<sup>4</sup>

66 Bisphenol A Exposure and Health Risks

ment in the pig [81].

cell apoptosis.

**4. Conclusion**

This work was supported by the National Science Centre (NCN), Poland [grant number: DEC‐2013/09/B/NZ7/00405].
