The action of retinoic acid on spermatogonia in the testis

For mammalian spermatogenesis to proceed normally, it is essential that the population of testicular progenitor cells, A undifferentiated spermatogonia (A_undiff), undergoes differentiation during the A to A1 transition that occurs at the onset of spermatogenesis. The commitment of the A_undiff population to differentiation and leaving a quiescent, stem-like state gives rise to all the spermatozoa produced across the lifespan of an individual, and ultimately determines male fertility. The action of all-trans retinoic acid (atRA) on the A_undiff population is the determining factor that induces this change. Sertoli cells, omnipresent, nurse cells within the mammalian testis are responsible for synthesizing the atRA that prompts this change in the neonatal testicular environment. The mechanism of atRA synthesis and signaling has been robustly explored and, in this review, we have summarized what is currently known about the action of testicular atRA at the onset of spermatogenesis. We have combined this with evidence gained from prominent genetic studies that have further elucidated the function of genes critical to atRA synthesis. We have additionally described the effects of the first pulse of atRA delivered to the germ cells of the testis, which has been investigated using WIN 18,446 treatment which prevents atRA synthesis and induces spermatogenic synchrony. This method provides unparalleled resolution into cell and stage specific testicular changes, and combined with transgenic animal models, has allowed researchers to elucidate much regarding the onset of spermatogenesis.