Heterogeneity in sexual bipotentiality and plasticity of granulosa cells in developing mouse ovaries

Kyoko Harikae, Kento Miura, Mai Shinomura, Shogo Matoba, Ryuji Hiramatsu, Naoki Tsunekawa, Masami Kanai-Azuma, Masamichi Kurohmaru, Ken ichirou Morohashi, Yoshiakira Kanai

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21 Citations (Scopus)

Abstract

In mammalian sex determination, SRY directly upregulates the expression of SOX9, the master regulatory transcription factor in Sertoli cell differentiation, leading to testis formation. Without SRY action, the bipotential gonadal cells become pre-granulosa cells, which results in ovarian follicle development. When, where and how pre-granulosa cells are determined to differentiate into developing ovaries, however, remains unclear. By monitoring SRY-dependent SOX9 inducibility (SDSI) in an Sry-inducible mouse system, we were able to identify spatiotemporal changes in the sexual bipotentiality/plasticity of ovarian somatic cells throughout life. The early pre-granulosa cells maintain the SDSI until 11.5 d.p.c., after which most pre-granulosa cells rapidly lose this ability by 12.0 d.p.c. Unexpectedly, we found a subpopulation of the pre-granulosa cells near the mesonephric tissue that continuously retains SDSI throughout fetal and early postnatal stages. After birth, these SDSI-positive pre-granulosa cells contribute to the initial round of folliculogenesis by the secondary follicle stage. In experimental sex reversal of 13.5-d.p.c. ovaries grafted into adult male nude mice, the differentiated granulosa cells re-acquire the SDSI before other signs of masculinization. Our data provide direct evidence of an unexpectedly high sexual heterogeneity of granulosa cells in developing mouse ovaries in a stage- and region-specific manner. Discovery of such sexually bipotential granulosa cells provides a novel entry point to the understanding of masculinization in various cases of XX disorders of sexual development in mammalian ovaries.

Original languageEnglish
Pages (from-to)2834-2844
Number of pages11
JournalJournal of cell science
Volume126
Issue number13
DOIs
Publication statusPublished - Jul 1 2013

All Science Journal Classification (ASJC) codes

  • Cell Biology

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    Harikae, K., Miura, K., Shinomura, M., Matoba, S., Hiramatsu, R., Tsunekawa, N., Kanai-Azuma, M., Kurohmaru, M., Morohashi, K. I., & Kanai, Y. (2013). Heterogeneity in sexual bipotentiality and plasticity of granulosa cells in developing mouse ovaries. Journal of cell science, 126(13), 2834-2844. https://doi.org/10.1242/jcs.122663