Research Paper Volume 14, Issue 22 pp 9200—9209

Rapamycin improves the quality and developmental competence of in vitro matured oocytes in aged mice and humans

Qiyu Yang1, , Juan Hu1, , Meng Wang1, , Na Guo1, , Liu Yang1, , Qingsong Xi1, &, , Lixia Zhu1, &, , Lei Jin1, &, ,

  • 1 Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Received: September 5, 2022       Accepted: November 17, 2022       Published: November 26, 2022
How to Cite

Copyright: © 2022 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Women over age 35 suffer from the inadequate number and poor quality of oocytes during assisted reproductive treatment, and making full use of the oocytes by in vitro maturation (IVM) is crucial. Rapamycin could improve the developmental competences of the post-maturation oocytes during in vitro aging, yet its effects on the IVM process of oocytes from an aged population were not clear. In this study, the immature oocytes from aged mice or older women underwent IVM with or without 10 nM rapamycin, followed by parthenogenetic activation or insemination and embryo culture. The developmental competence and quality of IVM oocytes in both groups were compared. The results showed that in aged mice, the maturation rate, activation rate, and cleavage rate of IVM oocytes were significantly elevated in the rapamycin group. Additionally, oocytes cultured with rapamycin presented decreased ROS levels, reduced chromosome aberration, and attenuated levels of γ-H2AX. During IVM of oocytes from older women, the GVBD rate, 24 h maturation rate, and 48 h maturation rate were increased in the rapamycin group, compared with those in the control group, although without significant differences. After intracytoplasmic sperm injection (ICSI) and further culture of human oocytes, the high-quality embryo rate in the rapamycin group was significantly elevated. Overall, rapamycin improved IVM outcomes of oocytes from aged mice and older women. The specific mechanism of the positive effects of rapamycin on IVM outcomes might be reducing ROS levels, mitigating DNA damage, and promoting developmental potential.


ART: assisted reproductive technologies; COCs: cumulus-oocyte complexes; COH: controlled ovarian hyperstimulation; DSB: double-strand break; FSH: follicle-stimulating hormone; GVBD: germinal vesicle breakdown; hCG: human chorionic gonadotropin; HQE: high-quality embryo; IBMX: isobutylmethylxanthine; ICSI: intracytoplasmic sperm injection; IVM: in vitro maturation; MMP: mitochondrial membrane potential; PA: parthenogenetic activation; PB1: first polar body; PESA/MESA: percutaneous/microsurgical epididymal sperm aspiration; PGT: preimplantation genetic testing; ROS: reactive oxygen species; TESA: testicular sperm aspiration.