Study Of Rapamycin Administration On Prolonging Ovarian Lifespan

In the past decades,it has been reported that inhibition of mammalian target of rapamycin(mTOR)pathway can prolong lifespans in both male and female animals.Different with man,the women have another life,that is ovary lifespan,which not only determines reproductive capacities,but also affects life qualities after menopause.Therefore,what we concern about is whether rapamycin also can prolong ovarian lifespan in females.In 2013,rapamycin(5mg/kg,ip,every other day for 3 months)was reported to increase the number of primordial follicles in rats,and their conclusion was that rapamycin could prolong female reproductive lifespan by inhibiting activating of primordial follicles.In fact,ovarian aging has more contents and ovarian lifespan cannot be determined only by the pool of primordial follicles.Another question,during the three months of rapamycin administrations,the rats' ovarian functions were seriously damaged.The rats had irregular estrous cycles and failed to mate with male rats.So,is this our purpose?Should we perform such experiment at the expense of normal reproductive capacities?The answer is not.In our study,we focus on ovarian aging and ovarian physiological functions,especially the reproductive lifespan after rapamycin removed.We used rapamycin(2mg/kg.ip)every day for only two weeks in both young(8weeks)and older(8-9months)mice.During the two weeks,rapamycin treatment mice had irregular estrous cycles.FSH,E2 and P were significantly deceased till two months after rapamycin removed.However,compared with controls,they had more primordial follicles.Expressions of some inflammatory factors,mainly IL-1?,IL-1? were decreased till four months after rapamycin removed.Sirtland Sirt6 were increased and it was the same case in older mice,which indicated that two-week rapamycin had certain effect on ovarian aging.More important,all mice were mated with normal males when they had regular estrous cycles for one year.After fertile test was complemented,we found that rapamycin could prolong ovarian lifespan by the increasing number of pubs and longer time of reproduction.Then we continued to investigate a new strategy for rapamycin which not only has beneficial effects in prolonging ovarian lifespan but also has no damage on ovarian functions,that is Rapamycin 2mg/kg ip once a week in obesity and normal female mice.In conclusion,unlike previous studies,we provided some new models of Rapamycin which can help to prolong ovarian lifespan.In our models,the side effects on ovarian functions was little,so we believe that it will be more practive in the future.