title: Rapamycin preserves the follicle pool reserve and prolongs the ovarian lifespan of female rats via modulating mTOR activation and sirtuin expression.
abstract: To maintain the normal length of female reproductive life, the majority of primordial follicles must be maintained in a quiescent state for later use. In this study, we aimed to study the effects of rapamycin on primordial follicle development and investigate the role of mTOR and sirtuin signaling. Rats were treated every other day with an intraperitoneal injection of rapamycin (5mg/kg) or vehicle. After 10weeks of treatment, ovaries were harvested for hematoxylin and eosin (HE) staining, and analysis by immunohistochemistry and Western blotting. HE staining showed that the number and percentage of primordial follicles in the rapamycin-treated group were twice the control group (P<0.001). Immunohistochemical analysis showed that mTOR and phosphorylated-p70S6K were extensively expressed in surviving follicles with strong staining observed in the cytoplasm of the oocyte. Western blotting showed decreased expression of phosphorylated mTOR and phosphorylated p70S6K in the rapamycin-treated group, and increased the expression of both SIRT1 and SIRT6 compared to the control group (P<0.05). Taken together, these results suggest that rapamycin may inhibit the transition from primordial to developing follicles and preserve the follicle pool reserve, thus extending the ovarian lifespan of female rats via the modulation of mTOR and sirtuin signalings.
authors.affiliation: Department of Gynaecology and Obstetrics of the First Affiliated Hospital, Medical College, Shantou University, Shantou 515041, China.
authors.forename: Xing-mei
authors.initials: XM
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Jin-jie
authors.initials: JJ
authors.lastname: Xu
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.forename: Wei-juan
authors.initials: WJ
authors.lastname: Liu
authors.forename: Xuan-hao
authors.initials: XH
authors.lastname: Lin
authors.forename: Yu-cai
authors.initials: YC
authors.lastname: Fu
authors.forename: Li-li
authors.initials: LL
authors.lastname: Luo
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003593:Cytoplasm / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D004801:Eosine Yellowish-(YS) / Q000378:metabolism; D030762:Estrous Cycle / Q000502:physiology; D005260:Female; D005298:Fertility / Q000187:drug effects; D006416:Hematoxylin / Q000378:metabolism; D008297:Male; D009865:Oocytes / Q000378:metabolism; D009929:Organ Size; D006080:Ovarian Follicle / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D019893:Ribosomal Protein S6 Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology*; D056565:Sirtuin 2 / Q000235:genetics / Q000378:metabolism*; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
chemical_list: C097475:Sirt2 protein, rat; C546845:mTOR protein, rat; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; D056565:Sirtuin 2; D037761:Sirtuins; C560607:sirtuin 6, rat; D004801:Eosine Yellowish-(YS); D020123:Sirolimus; D006416:Hematoxylin