Abstract
Unlike most organs that mature during the fetal period, the male reproductive system reaches maturity only at puberty with the commencement of spermatogenesis. Robust modelling of human testicular organogenesis in vitro would facilitate research into mechanisms of and factors affecting human spermatogenic failure and male fertility preservation in prepubertal tumor patients. Here, we report successful recapitulation of human testicular organogenesis in vitro from fetal gonadal ridge. Our model displayed the formation of mature seminiferous epithelium and self-renewing spermatogonia. Remarkably, in vitro-derived haploid spermatids have undergone meiotic recombination, and showed increased genetic diversity as indicated by genetic analysis. Moreover, these spermatids were able to fertilize oocytes and support subsequent blastocyst formation. The in vitro testicular organogenesis system described here will play an important role in elucidating the regulation of human testis development and maintaining male fertility in prepubertal cancer patients.
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Acknowledgements
We thank Peng Xiang for the 3β-HSD, CYP17A1 antibodies, Fei Gao for the AMH antibody, and Sigrid Eckardt for help with paper preparation. This work was supported by National Key R&D Program (2017YFA0103803), National Natural Science Foundation of China (31890784), and National Key R&D Program (2016YFA0500903, 2016YFA0503300).
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Conceptualization, X.G., F.D., Q.Z., and J.S.; Methodology, Q.C., Q.Zeng, Y.W., J.T., J.Y.; Investigation, Y.Y., L.L., H.Z., M.H., J.C., Q.Zhou, R.H., X.W., Z.Z., X.Y., J.H., D.H., J.L.; Writing (original draft), X.G., F.D., Q.Z. and J.S.; Writing (review and editing), X.G., F.D., Q.Z., and J.S.; Funding Acquisition, Y.Y., X.G., F.D., Q.Z., and J.S.; Supervision, X.G., F.D., Q.Z., and J.S.
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Yuan, Y., Li, L., Cheng, Q. et al. In vitro testicular organogenesis from human fetal gonads produces fertilization-competent spermatids. Cell Res 30, 244–255 (2020). https://doi.org/10.1038/s41422-020-0283-z
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DOI: https://doi.org/10.1038/s41422-020-0283-z
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