Roles of Stra8 and Tcergll in retinoic acid induced spermatogonial differentiation in mouse

• Published in: Biology of reproduction Vol. 105; no. 2; p. 503
• Main Authors: Sinha, Nilam, Whelan, Eoin C, Tobias, John W, Avarbock, Mary, Stefanovski, Darko, Brinster, Ralph L
• Format: Journal Article
• Language: English
• Published: Oxford University Press 01.08.2021
• Subjects: Cell differentiation; Genetic transcription; Stem cells; Tretinoin; Pennsylvania
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1093/biolre/ioab093

Retinoic acid (RA) induces spermatogonial differentiation, but the mechanism by which it operates remains largely unknown. We developed a germ cell culture assay system to study genes involved in spermatogonial differentiation triggered by RA. Stimulated by RA 8 (Stra8), a RA-inducible gene, is indispensable for meiosis initiation, and its deletion results in a complete block of spermatogenesis at the pre-leptotene/zygotene stage. To interrogate the role of Stra8 in RA mediated differentiation of spermatogonia, we derived germ cell cultures from the neonatal testis of both wild type and Stra8 knock-out mice. We provide the first evidence that Stra8 plays a crucial role in modulating the responsiveness of undifferentiated spermatogonia to RA and facilitates transition to a differentiated state. Stra8-mediated differentiation is achieved through the downregulation of a large portfolio of genes and pathways, most notably including genes involved in the spermatogonial stem cell self-renewal process. We also report here for the first time the role of transcription elongation regulator-1 like (Tcergll) as a downstream effector of RA-induced spermatogonial differentiation. Summary sentence The genes stimulated by retinoic acid 8 (Stra8) and transcription elongation regulator-1 like (Tcergll) are necessary in early-stage male germ cell differentiation induced by retinoic acid (RA). Stra8 is critical in modulating the responsiveness of undifferentiated spermatogonia to RA. Keywords: Stra8, Tcergll, SSC, spermatogonia, differentiation, transplantation.