Elsevier

Mechanisms of Development

Volume 128, Issues 11–12, January–February 2012, Pages 610-624
Mechanisms of Development

Retinoic acid metabolism links the periodical differentiation of germ cells with the cycle of Sertoli cells in mouse seminiferous epithelium

https://doi.org/10.1016/j.mod.2011.12.003Get rights and content
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Abstract

Homeostasis of tissues relies on the regulated differentiation of stem cells. In the epithelium of mouse seminiferous tubules, the differentiation process from undifferentiated spermatogonia (Aundiff), which harbor the stem cell functions, to sperm occurs in a periodical manner, known as the “seminiferous epithelial cycle”. To identify the mechanism underlying this periodic differentiation, we investigated the roles of Sertoli cells (the somatic supporting cells) and retinoic acid (RA) in the seminiferous epithelial cycle. Sertoli cells cyclically change their functions in a coordinated manner with germ cell differentiation and support the entire process of spermatogenesis. RA is known to play essential roles in this periodic differentiation, but its precise mode of action and its regulation remains largely obscure. We showed that an experimental increase in RA signaling was capable of both inducing Aundiff differentiation and resetting the Sertoli cell cycle to the appropriate stage. However, these actions of exogenous RA signaling on Aundiff and Sertoli cells were strongly interfered by the differentiating germ cells of intimate location. Based on the expression of RA metabolism-related genes among multiple cell types – including germ and Sertoli cells – and their regulation by RA signaling, we propose here that differentiating germ cells play a primary role in modulating the local RA metabolism, which results in the timed differentiation of Aundiff and the appropriate cycling of Sertoli cells. Similar regulation by differentiating progeny through the modulation of local environment could also be involved in other stem cell systems.

Highlights

► Undifferentiated spermatogonia differentiate periodically in mouse seminiferous tubules. ► Meiotic and haploid germ cells regulate the local retinoic acid (RA) metabolism. ► The increased RA triggers the differentiation of undifferentiated spermatogonia. ► RA also resets the functional cycle of somatic Sertoli cells. ► Thus, RA metabolism links the germ cell differentiation and Sertoli cell cycle.

Keywords

Spermatogonia
Retinoic acid
Seminiferous epithelial cycle
Sertoli cells

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