title: Xenobiotic effects on ovarian preantral follicles.
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.
authors.affiliation: Department of Physiology, University of Arizona, Tucson, Arizona, USA.
authors.forename: Connie J
authors.initials: CJ
authors.lastname: Mark-Kappeler
authors.forename: Patricia B
authors.initials: PB
authors.lastname: Hoyer
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Devine
mesh_terms: D000818:Animals; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D006801:Humans; D008597:Menstrual Cycle / Q000187:drug effects / Q000502:physiology; D023421:Models, Animal; D016273:Occupational Exposure / Q000009:adverse effects; D006080:Ovarian Follicle / Q000187:drug effects* / Q000254:growth & development*; D010053:Ovary / Q000187:drug effects / Q000502:physiology; D051381:Rats; D015262:Xenobiotics / Q000494:pharmacology*
chemical_list: D015262:Xenobiotics