Overaccumulation of Fat Caused Rapid Reproductive Senescence but not Loss of Ovarian Reserve in Mice.

Ovarian reserve and fertility are reduced by aging and a poor energy balance. To date, the relationships of high energy accumulation and aging with the ovarian reserve have not been elucidated. Here, the effects of obesity on the aging ovarian reserve were evaluated in a leptin-deficient (/) mouse model. Abnormal estrous cyclicity appeared as early as 6 weeks and worsened with aging. The blood level patterns of 17β-estradiol (E2), testosterone (T), and progesterone (P4) with aging were similar between lean and mice. The blood level of E2 but not P4 or T was similar at 24 weeks. Many more atretic follicles but fewer corpora lutea were observed in mice than in lean mice within all age groups. Anti-Müllerian hormone () mRNA levels were similar between genotypes. mRNAs were highly expressed in mice after 12 weeks. and mRNAs were highly expressed at 24 weeks in compared with lean mice. In addition, SOHLH1-positive primordial follicle counts were significantly increased in / mice at 24 weeks. The proportions of AMH-positive secondary and small antral follicles were similar between genotypes. Together, these results show that the ovarian reserve lasts longer in mice than in lean mice, suggesting that the loss of normal physiological or physical status causes decreased fertility at a young age in mice and that an increase in adipocytes without leptin, as in mice, can improve the ovarian reserve. Such knowledge can be applied to understanding reproductive dysfunction.