The Role of Differential Sensitivity to Retinoic Acid (RA) in Regulating Spermatogonial Fate

Abstract

In the mammalian testis, the foundation of spermatogenesis is provided by spermatogonial stem cells (SSCs); their progeny either remain as stem cells (following a self-renewal division) or proliferate as undifferentiated progenitors prior to differentiating in response to retinoic acid (RA) and later entering meiosis. The mechanisms regulating spermatogonial response to RA are undefined, and their identification would represent a key advance in our understanding of how spermatogonial fate is determined both at the beginning of spermatogenesis and throughout the male reproductive lifespan. This dissertation summarizes the results of an investigation into elusive mechanisms regulating a key switch fundamental to spermatogonial fate, the capacity of spermatogonia to respond to RA. The results support a novel model by which mammalian prospermatogonial and spermatogonial fates are regulated by intrinsic capacity to respond (or not) to the differentiation signal provided by RA prior to and concurrent with the initiation of spermatogenesis.