Endocrine-disrupting chemicals and female reproductive health: a growing concern

Female fertility and reproductive health depend on a series of developmental steps from embryogenesis through puberty, in addition to the proper functioning of the reproductive system in adulthood. Two important steps are the establishment of the ovarian reserve and development of the hypothalamic-pituitary-ovarian axis. During reproductive years, maintaining an adequate ovarian reserve of follicles as well as balanced neuroendocrine control of reproductive organs is crucial for fertility. Dysregulation of either of these events, during development or in adulthood, can lead to reproductive disorders. Over the past five decades, human fertility rates have declined, whereas the incidence of female reproductive disorders has risen, trends partially linked to environmental factors such as exposure to endocrine-disrupting chemicals (EDCs). Here we outline epidemiological and mechanistic evidence for how EDCs affect the ovarian reserve during early development, its maintenance during adulthood and the establishment of the hypothalamic-pituitary control of puberty and ovulation. Our Review not only reveals strong support for the role of EDC exposure in the development of female reproductive disorders such as abnormal puberty, impaired fertility, premature menopause or polycystic ovarian syndrome, but also highlights knowledge gaps, including the difficulty to prove causality between exposure and human disease manifestation.