Ovarian Metabolism of Xenobiotics

Abstract

At birth, the mammalian ovary contains a finite number of primordial follicles, which once depleted, cannot be replaced. Xenobiotic exposures can destroy primordial follicles resulting in premature ovarian failure and, consequently, early entry into menopause. A number of chemical classes can induce premature ovarian failure, including environmental, chemotherapeutic and industrial exposures. While our knowledge on the mechanistic events that occur in the ovary with chemical exposures is increasing, our understanding of the ovary's capacity to metabolize such compounds is less established. This review will focus on three chemicals for which information on ovarian metabolism is known: trichloroethylene, 7,12-dimethylbenz[a]anthracene and 4-vinylcyclohexene. The current state of understanding of ovarian bioactivation and detoxification processes for each will be described.

Scrambled eggs—Negative impacts of heat stress and chemical exposures on ovarian function in swine

“…Damage to growing or antral follicles can disrupt the estrous/menstrual cycle by altering ovarian steroid production and impairing ovulation, but the damage is temporary because these follicles can be replenished from the primordial follicle pool (Bhattacharya & Keating, 2011). Many factors can influence ovarian toxicity, including the dose and duration of the chemical exposure as well as the age at which the exposure occurs (Ganesan et al, 2014a). Some chemicals that are documented ovotoxicants include trichloroethylene, 7,12dimethylbenz(a)anthracene (DMBA), 4-vinylcyclohexene diepoxide (VCD), cyclophosphamide, pesticides, phthalates, per-and polyfluorinated substances and mycotoxins.…”

Investigating the ovarian impacts of Zearalenone exposure and influence of altered body composition on ovotoxicity

“…Environmental, occupational, medicinal, or xenoestrogenic chemicals can cause adverse effects on the female reproductive system [5,[132][133][134][135][136][137][138][139][140]. Chemicals that affect ovarian function are known as ovotoxicants and can target different stages of follicular development [16,135,141], leading to harmful effects on follicle development, decreased oocyte quality and ovulation, disruption of the estrous cycle, and altered hormonal production [135,137,[142][143][144]. Depletion of primordial follicles by ovotoxicants can cause POF and permanent infertility due to the depletion of the follicle pool that is irreplaceable [16,128,129,141,145,146].…”

“…Chemicals that affect ovarian function are known as ovotoxicants and can target different stages of follicular development [16,135,141], leading to harmful effects on follicle development, decreased oocyte quality and ovulation, disruption of the estrous cycle, and altered hormonal production [135,137,[142][143][144]. Depletion of primordial follicles by ovotoxicants can cause POF and permanent infertility due to the depletion of the follicle pool that is irreplaceable [16,128,129,141,145,146]. Damage to growing or antral follicles can disrupt the menstrual cycle by altering ovarian steroid production and impairing ovulation, but the damage is temporary because these follicles can be replaced from the primordial follicle pool [16,128,137,145].…”

“…Damage to growing or antral follicles can disrupt the menstrual cycle by altering ovarian steroid production and impairing ovulation, but the damage is temporary because these follicles can be replaced from the primordial follicle pool [16,128,137,145]. Many factors can influence ovarian toxicity, including concentration and duration of the chemical exposure as well as the age at which the exposure occurs [141]. Some chemicals that are known to be ovotoxicants include trichloroethylene, 7,12-dimethylbenz(a)anthracene, 4-vinylcyclohexene, cyclophosphamide, pesticides, phthalates, and zearalenone.…”

“…When GSH was added to cultured preovulatory follicles exposed to DMBA, apoptosis was prevented [162]. Skin tumor formation induced by DMBA was increased in glutathione Stransferase isoform pi (GSTP) null mice [163], suggesting that catalysis of conjugation by GSH to DMBA is mediated by GSTP [141]. The abundance of GSTP protein and mRNA in postnatal day 4 (PND4) cultured rat ovaries exposed to DMBA were increased prior to follicle loss induced by DMBA [156].…”