Trajectory of primordial follicle depletion is accelerated in obese mice in response to 7,12-dimethylbenz[a]anthracene exposure.

Abstract

Both obesity and exposure to environmental genotoxicants, such as 7,12-dimethylbenz[a]anthracene (DMBA), negatively impair female reproductive health. Hyperphagic lean KK.Cg-a/a (n = 8) and obese KK.Cg-Ay/J (n = 10) mice were exposed to corn oil as vehicle control (CT) or DMBA (1mg/kg/day) for 7d intraperitoneally, followed by a recovery period. Obesity increased liver and spleen weight (P < 0.05), and DMBA exposure decreased uterine weight (P < 0.05) in obese mice. Primordial follicle loss (P < 0.05) caused by DMBA exposure was observed in obese mice only. Primary (lean P < 0.1; obese P < 0.05) and secondary (lean P < 0.05, obese P < 0.1) follicle loss initiated by DMBA exposure continued across recovery. Reduced pre-antral follicle number in lean mice (P < 0.05), regardless of DMBA exposure, was evident with no effect on antral follicles or corpora lutea number. Immunofluorescence staining of DNA damage marker, γH2AX, did not indicate ongoing DNA damage but TRP53 abundance was decreased in follicles (P < 0.05) of DMBA-exposed obese mice. In contrast, increased (P < 0.05) superoxide dismutase was observed in the corpora lutea of DMBA-exposed obese mice and reduced (P < 0.05) TRP53 abundance was noted in preantral and antral follicles of DMBA-exposed obese mice. This study indicates that obesity influences ovotoxicity caused by a genotoxicant, potentially involving accelerated primordial follicle activation and hampering normal follicular dynamics.