Akr1b7 functions as a master regulator in ovarian aging

At the beginning of ovarian aging, the ovulation of immature oocytes is accelerated, leading to the arrest of ovulation despite the remaining oocytes. Here, RNA expression in the ovarian aging of mice is comprehensively analyzed during the estrous cycle after ovulation stimulation. The aldo-keto reductase Akr1b7 pathway transiently activated in the ovaries of young mice disappears in those of old mice. Akr1b7--/-- mice attenuate oocyte Akt activation essential for the follicular development in primordial follicles, and enhanced ovulation in immature oocytes. The estrous cycle is extended because of the prolonged diestrous stage by a sustained progesterone level in Akr1b7--/--mice ovaries, which is caused by the decline of Cyp17a1, a major metabolic enzyme of progesterone in Akr1b7-expressed theca cell layers. In summary, the decreased Akr1b7 pathway causes ovulation of immature oocytes and a prolonged estrous cycle, typical symptoms of ovarian aging.