Abstract
Vitamin A has been shown to be essential for a multitude of biological processes vital for mammalian development and homeostasis. Its active metabolite, retinoic acid (RA), is important for establishing and maintaining proper germ cell development. During spermatogenesis, the germ cells orient themselves in very distinct patterns, which have been organized into stages. There is evidence to show that, in the mouse, RA is needed for many steps during germ cell development. Interestingly, RA has been implicated as playing a role within the same two Stages: VII and VIII, where meiosis is initiated and spermiation occurs. The goal of this review is to outline this evidence, exploring the relevant players in retinoid metabolism, storage, transport, and signaling. Finally, this review will provide a potential model for how RA activity is organized across the murine stages of the spermatogenic cycle.
Highlights
Retinoic acid (RA) plays a vital role in many different developmental processes in mammals.Embryonically, retinoic acid (RA) is important in organogenesis, limb-bud development, proper neuronal development, and germ cell fate in the developing gonad
As germ cells progress through spermatogenesis, they travel from the basement membrane of the seminiferous tubule, where they start as undifferentiated spermatogonia, to the lumen, where they are released as spermatozoa
After the first wave of spermatogenesis, the preleptotenes are the source of RA for the undifferentiated spermatogonia, and retinoid metabolism in the Sertoli cells is no longer required for differentiation
Summary
Retinoic acid (RA) plays a vital role in many different developmental processes in mammals. RA is an important molecule for the proper function of many organs, such as skin, lung, kidney, liver, and testis function. Both high and low levels of RA have been shown to cause aberrant male germ cell development. Investigating the role that RA plays during spermatogenesis is vital to gain a better understanding of this complex biological process, but there are practical applications for furthering this research. Because vitamin A metabolism plays such a crucial role in spermatogenesis, perturbing RA synthesis and signaling is an excellent target for non-hormonal, male contraception. This review will provide a brief overview of both spermatogenesis and vitamin A metabolism, and will summarize the current evidence supporting the hypothesis that RA is the master regulator of the cycle of the seminiferous epithelium
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