Akr1b7 functions as a master regulator in ovarian aging [superSAGE]

At the beginning of ovarian aging, the ovulation of immature oocytes is accelerated, finally leading to the arrest of ovulation despite the remaining oocytes. Here RNA expression in ovarian aging of mice is comprehensively analyzed during the estrous cycle after ovulation stimulation, and an aldo-keto reductase Akr1b7 pathway transiently increased in the young ovary is eliminated in the aged mice. Akr1b7-/- mice enhance the ovulation of immature oocytes, and the KITL expression in Akr1b7-expressed stromal is attenuated, accompanied by oocyte Akt essential for the follicular development inactivation in primordial follicles. The estrous cycle is extended due to the prolonged diestrous stage by a sustained progesterone level in Akr1b7-/- mice ovaries, which is caused by the decline of Cyp17a1, a major metabolite enzyme of progesterone in Akr1b7-expressed theca cell layers. Taken together, the decreased Akr1b7 pathway causes the ovulation of immature oocytes and the prolonged estrous cycle, typical symptoms of ovarian aging. Overall design: Examination of comprehensive RNA analysis by superSAGE in YNG and OLD ovaries at 24h–96h after hCG administration.