Retinoic acid metabolism, signaling, and function in the adult testis

Abstract

The active metabolite of vitamin A, retinoic acid (RA), is absolutely required for the production of fertile sperm throughout the reproductive life of mammalian males. Our understanding of the regulation of spermatogenesis by vitamin A has grown substantially since the early 2000s. We now know that vitamin A must be converted to RA within the testis to exert its effects, which include regulating several key developmental events during spermatogenesis and both initiating and maintaining the cyclic nature of this process. The enzymes and receptors responsible for RA synthesis, metabolism, and signaling are well characterized, and extensive localization studies have shed some light on which cell types have the ability to generate, degrade, and/or respond to RA. However, we still understand very little about which of these proteins, and which testicular cell types, are responsible for normal RA function and what the direct outcomes of RA signaling are within the testis. In this chapter, we review our current understanding of how RA controls male germ cell development within the adult testis, discuss the effects of RA on Sertoli cell maturation and differentiation, and highlight key unanswered questions regarding how the Sertoli cells contribute to the overall balance of retinoid metabolism within the testis.