The Role of Retinoic Acid (RA) in Spermatogonial Differentiation1

Abstract

Retinoic acid (RA) directs the sequential, but distinct, programs of spermatogonial differentiation and meiotic differentiation that are both essential for the generation of functional spermatozoa. These processes are functionally and temporally decoupled, as they occur in distinct cell types that arise over a week apart, both in the neonatal and adult testis. However, our understanding is limited in terms of what cellular and molecular changes occur downstream of RA exposure that prepare differentiating spermatogonia for meiotic initiation. In this review, we describe the process of spermatogonial differentiation and summarize the current state of knowledge regarding RA signaling in spermatogonia.

Phosphoinositide signaling in sperm development

“…In adult mice, single SSCs (As) divide asynchronously to generate chains of 2-16 syncytial spermatogonia (Apr-Aal) that are undifferentiated (reviewed in [43,44] Retinoic acid-dependent PIP3 signaling drives conversion of undifferentiated (Aal) spermatogonia into differentiated (A1) spermatogonia (reviewed in [25,44,45]). Treatment of undifferentiated mouse spermatogonia with retinoic acid in vitro induces expression of the receptor tyrosine kinase Kit [46,47].…”

Meiotic initiation in chicken germ cells is regulated by Cyp26b1 and mesonephros

“…Previous studies have indicated that sex‐specific timing of meiosis depends on some inhibitory or inductive factors in the testis and ovary, respectively (Evans, Ford, & Lyon, ; C. W. Feng, Bowles, & Koopman, ; Ford et al, ; McLaren & Southee, ; Palmer & Burgoyne, ). There is a large body of evidence suggesting that retinoic acid (RA) and its genetic responder, Stra8 , are the critical meiotic gatekeepers in the embryonic ovary, whereas RA‐degrading activity of cytochrome p450 family 26 (CYP26) enzymes prevent the onset of meiosis in fetal testis (Baltus et al, ; Bowles et al, ; Busada & Geyer, ; Koubova et al, ; Mabie, ; Minkina et al, ).…”

Control of Germline Stem Cell Lineages by Diet and Physiology

“…Germ cell development from the stem cell stage to fully differentiated gametes is energetically costly and entails a large number of cellular processes that impose varying metabolic demands. It is not surprising, therefore, that multiple steps of gametogenesis are regulated by diet and other physiological factors (Ables et al 2012; Hubbard 2011; Gracida and Eckmann 2013b; Busada and Geyer 2016). …”