PMID- 31359237 OWN - NLM STAT- MEDLINE DCOM- 20200512 LR - 20240421 IS - 2509-2723 (Electronic) IS - 2509-2715 (Print) IS - 2509-2723 (Linking) VI - 41 IP - 4 DP - 2019 Aug TI - Effect of caloric restriction and rapamycin on ovarian aging in mice. PG - 395-408 LID - 10.1007/s11357-019-00087-x [doi] AB - Caloric restriction (CR) increases the preservation of the ovarian primordial follicular reserve, which can potentially delay menopause. Rapamycin also increases preservation on the ovarian reserve, with similar mechanism to CR. Therefore, the aim of our study was to evaluate the effects of rapamycin and CR on metabolism, ovarian reserve, and gene expression in mice. Thirty-six female mice were allocated into three groups: control, rapamycin-treated (4 mg/kg body weight every other day), and 30% CR. Caloric restricted females had lower body weight (P < 0.05) and increased insulin sensitivity (P = 0.003), while rapamycin injection did not change body weight (P > 0.05) and induced insulin resistance (P < 0.05). Both CR and rapamycin females displayed a higher number of primordial follicles (P = 0.02 and 0.04, respectively), fewer primary, secondary, and tertiary follicles (P < 0.05) and displayed increased ovarian Foxo3a gene expression (P < 0.05). Despite the divergent metabolic effects of the CR and rapamycin treatments, females from both groups displayed a similar increase in ovarian reserve, which was associated with higher expression of ovarian Foxo3a. FAU - Garcia, Driele N AU - Garcia DN AD - Faculdade de Nutricao, Universidade Federal de Pelotas, Pelotas, RS, Brazil. FAU - Saccon, Tatiana D AU - Saccon TD AD - Faculdade de Nutricao, Universidade Federal de Pelotas, Pelotas, RS, Brazil. FAU - Pradiee, Jorgea AU - Pradiee J AD - Faculdade de Medicina Veterinaria, Universidade Federal de Pelotas, Pelotas, RS, Brazil. FAU - Rincon, Joao A A AU - Rincon JAA AD - Faculdade de Medicina Veterinaria, Universidade Federal de Pelotas, Pelotas, RS, Brazil. FAU - Andrade, Kelvin R S AU - Andrade KRS AD - Faculdade de Nutricao, Universidade Federal de Pelotas, Pelotas, RS, Brazil. FAU - Rovani, Monique T AU - Rovani MT AD - Faculdade de Medicina Veterinaria, Universidade Federal de Pelotas, Pelotas, RS, Brazil. FAU - Mondadori, Rafael G AU - Mondadori RG AD - Instituto de Biologia, Universidade Federal de Pelotas, Pelotas, RS, Brazil. FAU - Cruz, Luis A X AU - Cruz LAX AD - Instituto de Biologia, Universidade Federal de Pelotas, Pelotas, RS, Brazil. FAU - Barros, Carlos C AU - Barros CC AD - Faculdade de Nutricao, Universidade Federal de Pelotas, Pelotas, RS, Brazil. FAU - Masternak, Michal M AU - Masternak MM AD - College of Medicine, Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL, USA. AD - Department of Head and Neck Surgery, The Greater Poland Cancer Centre, Poznan, Poland. FAU - Bartke, Andrzej AU - Bartke A AD - Departments of Internal Medicine and Physiology, Southern Illinois University School of Medicine, Springfield, IL, USA. FAU - Mason, Jeffrey B AU - Mason JB AD - Department of Animal, Dairy and Veterinary Sciences, Center for Integrated BioSystems, School of Veterinary Medicine, Utah State University, Logan, UT, USA. FAU - Schneider, Augusto AU - Schneider A AUID- ORCID: 0000-0002-3410-2860 AD - Faculdade de Nutricao, Universidade Federal de Pelotas, Pelotas, RS, Brazil. LA - eng GR - R03 AG059846/AG/NIA NIH HHS/United States GR - R15 AG059190/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20190729 PL - Switzerland TA - Geroscience JT - GeroScience JID - 101686284 RN - 0 (Forkhead Box Protein O3) RN - 0 (FoxO3 protein, mouse) RN - 0 (Immunosuppressive Agents) RN - 63231-63-0 (RNA) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Animals MH - Body Weight MH - *Caloric Restriction MH - Female MH - Forkhead Box Protein O3/genetics/metabolism MH - Gene Expression MH - Immunosuppressive Agents/*pharmacology MH - Insulin Resistance MH - Mice, Inbred C57BL MH - Ovarian Follicle/*pathology MH - *Ovarian Reserve MH - Ovary/metabolism MH - RNA/metabolism MH - Sirolimus/*pharmacology PMC - PMC6815295 OTO - NOTNLM OT - FOXO3a OT - Ovarian reserve OT - Rapamycin OT - mTOR COIS- The authors declare that they have no conflict of interest. EDAT- 2019/07/31 06:00 MHDA- 2020/05/19 06:00 PMCR- 2019/07/29 CRDT- 2019/07/31 06:00 PHST- 2019/06/07 00:00 [received] PHST- 2019/07/16 00:00 [accepted] PHST- 2019/07/31 06:00 [pubmed] PHST- 2020/05/19 06:00 [medline] PHST- 2019/07/31 06:00 [entrez] PHST- 2019/07/29 00:00 [pmc-release] AID - 10.1007/s11357-019-00087-x [pii] AID - 87 [pii] AID - 10.1007/s11357-019-00087-x [doi] PST - ppublish SO - Geroscience. 2019 Aug;41(4):395-408. doi: 10.1007/s11357-019-00087-x. Epub 2019 Jul 29.