Abstract
The lack of hormone-responsive follicles is a major challenge in treating infertility/subfertility in women with premature ovarian insufficiency or diminished ovarian reserve. In this study, we demonstrate that securinine, a neurological drug, can be repurposed to promote small follicle growth. In aged mice, intraovarian injection of securinine significantly enhances follicular development and improves fertility, yielding healthy offspring. Mechanistically, single-cell RNA sequencing reveals that securinine promotes follicular development by alleviating the negative regulation from the stromal extracellular matrix on granulosa cells. Furthermore, intraovarian injection of securinine in aged cynomolgus macaques effectively stimulates the development of small follicles into large antral follicles. Our findings highlight securinine as a promising candidate for ultrasound-guided ovarian injection for treating infertility/subfertility in women with premature ovarian insufficiency, diminished ovarian reserve, or advanced maternal age. As a small molecule drug, intraovarian securinine injection offers clinical advantages that avoid complex preparation procedures required for platelet-rich plasma or stem cell-based therapies.
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Data availability
The raw sequence data reported in this paper have been deposited in the Genome Sequence Archive in the National Genomics Data Center under the accession code CRA020721. Source data are provided in this paper.
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Acknowledgements
We thank our many colleagues and other researchers for their constructive discussions. This study was supported by grants from the Shenzhen-Hong Kong-Macau Type C Project of the Shenzhen Municipal Science, Technology, and Innovation Commission (SGDX20230821091501011 to K.L.) and the Ningbo Major Research and Development Plan Project (2024Z232 to Y.Z.). Illustration diagrams in this manuscript (Figs. 5a, 6a and Supplementary Fig. 2a) were created with BioRender.com (Liu, D., 2026).
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Y.Z., W.S.B.Y., and K.L. designed the study. Y.Z., D.T.L., S.Z.D., X.D.Z., Y.T.S., Y.H.Z., Q.Z., J.K.G., and Y.X. performed the experiments and analyzed the data. Y.Z. and Z.X.L. analyzed the scRNA-seq data. Y.Z. D.T.L., Z.X.L., W.S.B.Y., and K.L. interpreted the results. T.R.W., H.N.L., J.Z., K.K.L.C., and Y.L. discussed the results. Y.Z., D.T.L., W.S.B.Y., and K.L. wrote the manuscript with input from all authors.
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Zhao, Y., Liu, D., Lin, Z. et al. Intraovarian injection of securinine stimulates the growth of small ovarian follicles by reducing stromal suppression. Nat Commun (2026). https://doi.org/10.1038/s41467-026-71691-7
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DOI: https://doi.org/10.1038/s41467-026-71691-7
