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  2. Differential RA responsiveness directs formation of functionally distinct spermatogonial populations at the initiation of spermatogenesis in the mouse

Differential RA responsiveness directs formation of functionally distinct spermatogonial populations at the initiation of spermatogenesis in the mouse

  • Development. 2019 May 13;146(12):dev173088. doi: 10.1242/dev.173088.
Ellen K Velte 1 Bryan A Niedenberger 1 Nicholas D Serra 1 Anukriti Singh 2 Lorena Roa-DeLaCruz 2 Brian P Hermann 2 Christopher B Geyer 3 4
Affiliations

Affiliations

  • 1 Departments of Anatomy and Cell Biology, Brody School of Medicine, East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC 27834, USA.
  • 2 Department of Biology, University of Texas at San Antonio, San Antonio, TX 78249, USA.
  • 3 Departments of Anatomy and Cell Biology, Brody School of Medicine, East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC 27834, USA geyerc@ecu.edu.
  • 4 East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC 27834, USA.
Abstract

In the mammalian testis, sustained spermatogenesis relies on spermatogonial stem cells (SSCs); their progeny either remain as stem cells (self-renewal) or proliferate and differentiate to enter meiosis in response to retinoic acid (RA). Here, we sought to uncover elusive mechanisms regulating a key switch fundamental to spermatogonial fate: the capacity of spermatogonia to respond to RA. Using the developing mouse testis as a model, we found that spermatogonia and precursor prospermatogonia exhibit a heterogeneous capacity to respond to RA with at least two underlying causes. First, progenitor spermatogonia are prevented from responding to RA by catabolic activity of Cytochrome P450 family 26 Enzymes. Second, a smaller subset of undifferentiated spermatogonia enriched for SSCs exhibit catabolism-independent RA insensitivity. Moreover, for the first time, we observed that precursor prospermatogonia are heterogeneous and comprise subpopulations that exhibit the same differential RA responsiveness found in neonatal spermatogonia. We propose a novel model by which mammalian prospermatogonial and spermatogonial fates are regulated by their intrinsic capacity to respond (or not) to the differentiation signal provided by RA before, and concurrent with, the initiation of spermatogenesis.

Keywords

CYP26; Prospermatogonia; Retinoic acid; Spermatogenesis; Spermatogonia; Testis.

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