Demystifying Bisphenol A-Induced Alterations in Hypothalamic-Pituitary-Ovarian Functions Leading to Polycystic Ovarian Syndrome

In recent decade, polycystic ovarian syndrome (PCOS) has become one of the main fertility disorders in females. Other than genetic factors, the etiology of this disease includes environmental factors, especially endocrine disrupting compounds (EDC). Bisphenol A (BPA) is a prominent EDC enormously used in manufacturing of various substances. Increased exposure to these substances on a daily basis throughout life, from prenatal to adult stages, has resulted in deleterious changes in female reproductive system. These changes include PCOS-like phenotypes such as hyperandrogenism, cystic ovaries and anovulation. Although studies in human are limited, several reports are available in animal models wherein BPA has been shown to directly affect ovarian development, folliculogenesis and steroidogenesis, thereby causing PCOS-like symptoms. Hypothalamus and pituitary are considered to be the most significant endocrine tissues involved in maintaining the structure and functions of ovary. BPA being an endocrine disruptor severely affects these tissues by modulating the synthesis and release of gonadotropin releasing hormone and gonadotropins from hypothalamus and pituitary, respectively. However, in light of reports available, effect of BPA on hypothalamus and pituitary do not corroborate with those on ovary. The current review suggests that BPA-induced PCOS-like phenotypes might be due to its direct action on ovary while alteration in hypothalamo-pituitary-ovarian axis seems to play a minor role. The authors through this review also intend to direct the attention of readers and policy makers towards the fact that despite the well-known negative effects of BPA exposure, manufacturing and use of BPA-containing substances is continuing, especially in developing countries.