New work pinpoints stem cells that give rise to ovarian thecal cells, which together with granulosa cells and oocytes, form ovarian follicles. Thecal cells secrete steroid substrates required for production of the hormone estrogen, and aggregate in layers that ensheath and structurally support ovarian follicles, the growth of which is referred to as folliculogenesis.
Although much is known about the factors regulating mature thecal cell function, immature ‘ancestors’ of thecal cells have not been isolated, and the processes influencing thecal cell development and localization within the ovary remain uncharacterized.
Although originally intending to isolate elusive stem cells capable of giving rise to oocytes, a team led by Atsuo Ogura, a scientist at the RIKEN BioResource Center in Tsukuba, instead identified, and managed to produce in a dish, thecal stem cells1.
The researchers cultured cells from ovaries of newborn mice in a medium containing growth factors but lacking serum. In just a few days, cellular ‘colonies’ appeared, grew rapidly and released oocytes. However, unlike stem cells, which undergo continuous cell division, these oocytes did not replicate their DNA and thus likely arose from pre-existing immature oocytes, rather than from oocyte stem cells.
However, further analysis of proliferating colonies revealed the existence of a stem cell-like population that expressed genes specific to thecal cells. To determine whether these cells could give rise to thecal cells, the researchers added serum and/or the hormones to which thecal cells in follicles are normally exposed.
When confronted with serum and hormones, this population underwent morphological changes associated with steroid production, released steroids into the culture medium, and activated genes expressed exclusively in mature thecal cells. Co-culture with granulosa cells further enhanced thecal cell differentiation of this population.
Lastly, the researchers subjected these putative thecal stem cells to the ultimate test—the ability to localize in layers surrounding actual mouse ovarian follicles. Remarkably, within two weeks of intra-ovarian transplantation, fluorescently labelled culture-derived thecal stem cells were incorporated, like bona fide thecal cells, within thecal layers of ovarian follicles (Fig. 1).
This tractable method for the production of large populations of thecal cells and their precursors will likely aid future experiments investigating thecal cell biology. “By using thecal stem cells isolated in this way, we will be able to reproduce the entire process of folliculogenesis in a dish. These studies may lead to a new treatment for folliculogenesis failure,” says Ogura.
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. Isolation, characterization and in vitro and in vivo differentiation of putative thecal stem cells. Proceedings of the National Academy of Sciences USA 104, 12389–12394 (2007).
