PMID- 38532230 OWN - NLM STAT- Publisher LR - 20240327 IS - 1933-7205 (Electronic) IS - 1933-7191 (Linking) DP - 2024 Mar 26 TI - Enhancing Oocyte Quality in Aging Mice: Insights from Mesenchymal Stem Cell Therapy and FOXO3a Signaling Pathway Activation. LID - 10.1007/s43032-024-01509-8 [doi] AB - Ovarian aging reduced the quality of oocytes, resulting in age-related female infertility. It is reported that mesenchymal stem cells (MSCs) therapy can improve age-related ovarian function decline and the success rate of in vitro maturation (IVM) in assisted reproductive therapy. In order to investigate the effectiveness and mechanisms of MSCs to enhance oocyte quality of cumulus oocyte complexes (COCs) in advanced age, this study focus on the respective functional improvement of oocytes and granulosa cells (GCs) from aging mice and further to explore and verify the possible mechanisms. Here, we studied a popular but significant protein of follicular development, Forkhead box O-3a (FOXO3a), which is a transcription factor that mediates a variety of cellular processes, but the functions of which in regulating oocyte quality in MSCs therapy still remain inconclusive. In this study, the RNA-seq data of metaphase II (MII) oocytes and GCs isolated from COCs confirmed that, GCs of immature follicles show the most potential to be the targeted cells of bone marrow mesenchymal stem cells (BMSCs) by FOXO3a signaling pathway. Furthermore, we demonstrated the effectiveness of BMSCs co-culture with aging COCs to enhance oocyte quality and found its mechanism to function via ameliorating the biological function of GCs by alleviating FOXO3a levels. These results provide significant fundamental research on MSCs therapy on ovarian aging, as well as offering guidance for raising the success rate of assisted reproductive technology such IVM in clinical and non-clinical settings. CI - (c) 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation. FAU - Wang, Lingjuan AU - Wang L AD - Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. AD - National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. AD - Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Liu, Yang AU - Liu Y AD - Department of Obstetrics and Gynecology Reproductive Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China. FAU - Song, Yinhua AU - Song Y AD - National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. AD - Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Mei, Qiaojuan AU - Mei Q AD - Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Mou, Hongbei AU - Mou H AD - Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Wu, Jiachen AU - Wu J AD - National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Tang, Xinyu AU - Tang X AD - National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Ai, Jihui AU - Ai J AD - National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. AD - Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Li, Kezhen AU - Li K AD - National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Xiao, Houxiu AU - Xiao H AD - Wuhan National High Magnetic Field Center, Huazhong University of Science and Technology, Wuhan, China. FAU - Han, Xiaotao AU - Han X AD - Wuhan National High Magnetic Field Center, Huazhong University of Science and Technology, Wuhan, China. FAU - Lv, Liqun AU - Lv L AD - Wuhan Kangjian Maternal and Infant Hospital, Wuhan, China. FAU - Li, Huaibiao AU - Li H AD - Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Zhang, Ling AU - Zhang L AD - Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. zhling312@163.com. FAU - Xiang, Wenpei AU - Xiang W AUID- ORCID: 0000-0001-9510-116X AD - Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. wpxiang2010@gmail.com. LA - eng GR - 2017YFC1002002)/the National Key Research and Development Program of China/ GR - 82101700/the National Natural Science Foundation of China/ PT - Journal Article DEP - 20240326 PL - United States TA - Reprod Sci JT - Reproductive sciences (Thousand Oaks, Calif.) JID - 101291249 SB - IM OTO - NOTNLM OT - In vitro maturation OT - Aging OT - BMSCs OT - FOXO3a OT - Granulosa cells OT - Oocyte quality EDAT- 2024/03/27 06:43 MHDA- 2024/03/27 06:43 CRDT- 2024/03/27 00:36 PHST- 2023/12/31 00:00 [received] PHST- 2024/03/01 00:00 [accepted] PHST- 2024/03/27 06:43 [medline] PHST- 2024/03/27 06:43 [pubmed] PHST- 2024/03/27 00:36 [entrez] AID - 10.1007/s43032-024-01509-8 [pii] AID - 10.1007/s43032-024-01509-8 [doi] PST - aheadofprint SO - Reprod Sci. 2024 Mar 26. doi: 10.1007/s43032-024-01509-8.