Xenobiotic Effects on Ovarian Preantral Follicles1

Abstract

Women are born with a finite population of ovarian follicles, which are slowly depleted during their reproductive years until reproductive failure (menopause) occurs. The rate of loss of primordial follicles is determined by genetic and environmental influences, but certain toxic exposures can accelerate this process. Ionizing radiation reduces preantral follicle numbers in rodents and humans in a dose-dependent manner. Cigarette smoking is linked to menopause occurring 1-4 yr earlier than with nonsmokers, and components of smoke, polycyclic aromatic hydrocarbons, can cause follicle depletion in rodents or in ovaries in vitro. Chemotherapeutic agents, such as alkylating drugs and cisplatin, also cause loss of preantral ovarian follicles. Effects depend on dose, type, and reactivity of the drug, and the age of the individual. Evidence suggests DNA damage may underlie follicle loss induced by one common alkylating drug, cyclophosphamide. Occupational exposures have also been linked to ovarian damage. In an industrial setting, 2-bromopropane caused infertility in men and women, and it can induce ovarian follicle depletion in rats. Solvents, such as butadiene, 4-vinylcyclohexene, and their diepoxides, can also cause specific preantral follicle depletion. The mechanism(s) underlying effects of the latter compound may involve alterations in apoptosis, survival factors such as KIT/Kit Ligand, and/or the cellular signaling that maintains primordial follicle dormancy. Estrogenic endocrine disruptors may alter follicle formation/development and impair fertility or normal development of offspring. Thus, specific exposures are known or suspected of detrimentally impacting preantral ovarian follicles, leading to early ovarian failure.

There is a Positive Correlation Between Socioeconomic Status and Ovarian Reserve in Women of Reproductive Age

“…In a broader sense, circulating hormones in pregnancy may impact ovarian reserve. However, exposure to social factors and environmental contaminants also should be considered [28]. Prolonged exposure after birth and during adulthood may also have an impact on ANM.…”

Protective effect of mirtazapine and hesperidin on cyclophosphamide-induced oxidative damage and infertility in rat ovaries

“…With high dose and longer duration, oocyte number is reduced drastically resulting in premature ovarian failure and premature menopause. 1 This is mostly attributed to ovarian toxicity due to the cumulative doses of CP. CP and its toxic metabolites interfere with intracellular antioxidation systems that play an important role in detoxifying the reactive oxygen species (ROS).…”

Quantitative variations in ovarian follicles of female Sprague Dawley rats after exposure to low dose gamma radiation

“…It in turn might cause pronounced damage to oocyte. Ionizing radiation reduces preantral follicle numbers in rodents and humans in a dose-dependent manner (Mark-Kappeler et al, 2011). In female rats exposed in-utero to 1.5 Gy gamma-irradiation, severe depletion in oocytes was evidenced by premature ovarian failure from 6 months by Mazaud et al (2002).…”