Germ Cell Depletion Influenced Neuromuscular, Sensory, Renal and Metabolic Function in PostReproductive Female Mice

Numerous observations suggest a relationship between reproduction and health. This relationship has been difficult to define, particularly in mammals. At menopause, germ cell-diminished ovaries are relatively senescent. In mice, replacement of these senescent ovaries with young, actively cycling ovaries significantly increased life and health span in recipients. While we were successful in extending life and health span in postreproductive females, these experiments were not designed to distinguish between the contributions of ovarian hormones from actively cycling germ cells and the somatic tissue components of the ovaries. In the current study, we used 4-vinylcyclohexene diepoxide to deplete ovarian germ cells in 28-day old CBA/J mice. These mice were evaluated at 13 months of age to determine if depletion of ovarian germ cells influenced health span. Germ cell-depletion significantly reduced musculoskeletal and renal function, but improved body composition at 13 months of age. Percent fat mass was reduced 9% and lean mass was increased 5% in 13-month old, germ cell-depleted mice. There was no significant age-associated change in glucose tolerance. However, germ cell-depleted mice displayed changes suggestive of early insulin resistance in response to a glucose tolerance test. Germ cell-depletion displayed a strong, positive trend on sensory function, but did not influence cognitive behavior or immune function. These finding suggest that the ovarian influence on health is not exclusive to the germ cells. Together, these findings provide strong incentive for further investigation of the influence of the reproductive and non-reproductive function of ovarian germ and somatic cells and hormones in the preservation of health