Evidence map›Paper›PMID 42286606›Full record

ArticleStem cell research & therapy2026

BDNF secreted by mesenchymal stem cells ameliorates the accelerated meiotic progression in aged mouse oocytes by activating the PI3K/AKT pathway.

Xin Mi, Jiali Zhou, Caiyi Chen, Jing Zhou, Yajuan Yang, Hongyan Wang, Xue Jiao, Yingying Qin, Zi-Jiang Chen, Shidou Zhao

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Article in Stem cell research & therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Xin MiState Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, 250012, Shandong, China.
Jiali ZhouState Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, 250012, Shandong, China.
Caiyi ChenState Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, 250012, Shandong, China.
Jing ZhouState Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, 250012, Shandong, China.
Yajuan YangState Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, 250012, Shandong, China.
Hongyan WangDivision of Cell, Developmental and Integrative Biology, School of Medicine, South China University of Technology, Guangzhou, 510006, Guangdong, China.
Xue JiaoState Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, 250012, Shandong, China.
Yingying QinState Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, 250012, Shandong, China.
Zi-Jiang ChenState Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, 250012, Shandong, China.
Shidou ZhaoState Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, 250012, Shandong, China. shidouzhao@sdu.edu.cn.

Funding

CAMS Innovation Fund for Medical Sciences 2021-I2M-5-001National Key Research and Development Program of China 2024YFC2706600National Natural Science Foundation of China 32370906National Natural Science Foundation of China 32588201National Natural Science Foundation of China 82160286National Natural Science Foundation of China 82421004Natural Science Foundation of Shandong Province for Distinguished Young Scholars ZR2023JQ031Specific Research Fund of The Innovation Platform for Academicians of Hainan Province YSPTZX202310Taishan Scholars Program for Young Experts of Shandong Province tsqn202211370
6 · The paper itself

Abstract

backgroundOocyte aneuploidy is a major contributor to age-related fertility decline, but the effective treatments are still unavailable. The spindle assembly checkpoint (SAC), which functions to maintain chromosomal euploidy in oocytes, may become impaired with aging, manifesting primarily as an aberrant acceleration of meiotic progression. In the present study, we investigated the effects, effective components, and molecular mechanisms of the secretome of mesenchymal stem cells (MSC-sec) in reducing aneuploidy by alleviating the accelerated meiotic progression of aged mouse oocytes.

methodsMSC-sec was added to oocyte culture medium and its effects on aged oocytes were evaluated through analysis of meiotic process, chromosome alignment, the expression and localization of SAC proteins BubR1 and ZW10. The critical role of the PI3K/AKT pathway was confirmed by application of the inhibitor LY294002. Exogenous brain-derived neurotrophic factor (BDNF) or BDNF neutralizing antibodies were used to identify the effective components of MSC-sec. The in vitro effects of 7,8-dihydroxyflavone (7,8-DHF), a BDNF receptor agonist, were validated through PI3K/AKT and ERK1/2 pathway activity, meiotic progression and aneuploidy assays, while its in vivo effects were assessed by oocyte quality and early embryo development following intraperitoneal injection.

resultsMSC-sec could ameliorate age-related accelerated meiotic progression and increase the expression of BubR1 and ZW10 at the kinetochore in mouse oocyte. MSC-sec treatment activates the PI3K/AKT pathway in aged oocytes, and its effect on meiotic progression can be blocked by the PI3K inhibitor LY294002. BDNF is identified as the effective component of MSC-sec in decelerating the meiotic progression. In vitro application of 7,8-DHF ameliorated the accelerated meiotic progression and reduced the aneuploidy rate in aged oocytes, effectively mimicking the effects of BDNF. In vivo administration of 7,8-DHF significantly enhanced oocyte quality and early embryo development in aged mice.

conclusionsWe found that BDNF secreted by MSCs ameliorates the accelerated meiotic progression in aged mouse oocytes by activating the PI3K/AKT pathway, which may be attributed to an improvement in SAC function. Our study elucidates the molecular mechanism and effective component of MSC-sec to alleviate aneuploidy of aged oocytes, providing an experimental foundation for the clinical translation of BDNF or its alternative 7,8-DHF in improving the quality and development potential of oocytes from aged women.

Indexed as

Brain-Derived Neurotrophic FactorMeiosisMesenchymal Stem CellsOocytesPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktAneuploidyAnimalsCell Cycle ProteinsFemaleMiceProtein Serine-Threonine KinasesSignal TransductionBdnf protein, mouseBrain-Derived Neurotrophic FactorBub1b protein, mouseCell Cycle ProteinsPhosphatidylinositol 3-KinasesProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktAgingBrain-derived neurotrophic factorMesenchymal stem cellsOocyte qualityPI3K/AKT signaling pathway

Identifiers

PMID42286606
PMCPMC13501573

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.