All your eggs in one basket : mechanisms of xenobiotic induced female reproductive senescence

The irreplaceable mammalian primordial follicle represents the basic unit of female fertility, serving as the primary source of all developing oocytes in the ovary. These primordial follicles remain quiescent, often for decades, until recruited into the growing pool throughout a woman’s adult reproductive years. Once recruited, <1% will reach ovulation, with the remainder undergoing an apoptotic process known as atresia (Hirshfield, 1991). Menopause, or ovarian senescence, occurs when the pool of primordial follicles becomes exhausted. Pre-mature ovarian failure (POF; or early menopause) is an ovarian defect characterised by the premature loss of menstrual cyclicity before the age of 40, well below the median age of natural menopause (51 years). Approximately 1-4% of the female population suffers from this condition, making POF a significant contributor of female infertility (Coulam et al., 1986). There is now a growing body of evidence which suggests that foreign synthetic chemicals, also known as xenobiotics, are capable of causing POF by inducing premature follicular depletion. Indeed, exposure to pesticides, workplace chemicals, chemotherapeutic agents and cigarette smoke have all been associated with primordial follicle reduction resulting in premature ovarian senescence (Hoyer and Devine, 2001; Mattison et al., 1983a, 1983b; Sobinoff et al., 2010, 2011). In addition to infertility, the loss of ovarian hormones which accompanies POF has been connected with an increased risk of early morbidity and mortality (Shuster et al., 2010). With current statistics indicating an increasing trend in western women opting to delay childbirth, xenobiotic exposure could have long lasting repercussions for both the fertility and long term health of these women. In this review we discuss the susceptible nature of primordial follicles and the consequences of xenobiotic induced POF. We then examine the mechanisms of ovotoxicity for environmental toxicants and xenobiotics known to target immature follicles, and discuss the development of novel methods of wildlife fertility control utilizing these ovotoxicants.