THE ROLE OF RETINOIC ACID IN DIRECTING INITIATION OF SPERMATOGENESIS IN THE MOUSE

Abstract

The basic tenets of gametogenesis are conserved among metazoans. After lineage commitment, germ cells proliferate, complete meiosis, and then differentiate into gametes capable of fertilization. In the mouse, spermatogenesis begins at approximately postnatal day (P) 3-4, as prospermatogonia transition into distinct populations of spermatogonia. Some prospermatogonia become spermatogonial stem cells (SSCs) that provide a consistent source of gametes throughout the male reproductive lifespan. The remaining prospermatogonia proliferate and directly differentiate (without going through an SSC stage) in response to retinoic acid (RA) to eventually enter meiosis at P10. The pathways and cellular mechanisms that direct this critical cell fate decision are poorly defined. This dissertation summarizes the results of an examination of the cellular and molecular changes that occur downstream of RA signaling that direct prospermatogonia at P0-2 to transition to differentiating spermatogonia at P3-4. The results support a novel mechanism by which RA directs spermatogonial differentiation during spermatogenesis.