Isolation, characterization, and in vitro and in vivo differentiation of putative thecal stem cells

Arata Honda, Michiko Hirose, Kenshiro Hara, Shogo Matoba, Kimiko Inoue, Himomi Miki, Hitoshi Hiura, Mito Kanatsu-Shinohara, Yoshiakira Kanai, Tomohiro Kono, Takashi Shinohara, Atsuo Ogura

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81 Citations (Scopus)

Abstract

Although ovarian theca cells play an indispensable role in folliculogenesis by providing follicular structural integrity and steroid substrates for estrogen production, little information is available about their recruitment, growth, and differentiation because their immature forms have not been identified. We have isolated putative thecal stem cells with the ability to self-renew and differentiate in vivo and in vitro. They are similar to fibroblasts in morphology and proliferate in vitro as round colonies with a homogenous cell population. They were induced to differentiate into early precursors and steroidogenic cells in a stepwise manner after treatment with serum, luteinizing hormone, and paracrine factors from granulosa cells. At each differentiation step, these cells displayed appropriate gene expression and morphological markers and later secreted androstenedione. The fully mature morphology was achieved by coculture with isolated granulosa cells. When transplanted into the ovaries, the putative thecal stem cells colonized exclusively in the ovarian interstitium and the thecal layer of follicles as differentiated cells. Thus, thecal stem cells appear to be present in neonatal ovaries and can be isolated, purified, and induced to differentiate in vitro. Thecal stem cells could provide an invaluable in vitro experimental system to study interactions among the oocytes, granulosa cells, and theca cells during normal folliculogenesis and to study ovarian pathology caused by theca cell dysfunction.

Original languageEnglish
Pages (from-to)12389-12394
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number30
DOIs
Publication statusPublished - 2007 Jul 24

Keywords

  • Follicle
  • Oocyte
  • Ovary

ASJC Scopus subject areas

  • General

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    Honda, A., Hirose, M., Hara, K., Matoba, S., Inoue, K., Miki, H., Hiura, H., Kanatsu-Shinohara, M., Kanai, Y., Kono, T., Shinohara, T., & Ogura, A. (2007). Isolation, characterization, and in vitro and in vivo differentiation of putative thecal stem cells. Proceedings of the National Academy of Sciences of the United States of America, 104(30), 12389-12394. https://doi.org/10.1073/pnas.0703787104