Differential retinoic acid responses across testicular development in vitro

Abstract

Spermatogonial differentiation is controlled by distinct spatial and temporal activities of metabolizing enzymes and signaling molecule formation. In vitro models are reductionist ways to examine the interactions between Sertoli cells and spermatogonial stem cells, which may be therapeutic targets for infertility that cause non-obstructive azoospermia, due to either Sertoli-cell only syndrome, hypospermatogenesis or maturation arrest. Here, we find that nanomolar doses of isotretinoin are sufficient to drive Stra8 expression in vitro, an interaction that is both dose-dependent and inhibitable. We compare complex in vitro models (CIVMs) seeded from cells isolated post-natal day 5 (PND 5) and post-natal day 10 (PND 10) Sprague Dawley rat testis. The CIVMs maintain metabolic capacity to produce bioactive retinoids form retinol. We also investigate the impact of common media supplementations on spermatogonial phenotype and find that they can impact the expression of Stra8 and Plzf as markers of early differentiating and undifferentiated spermatogonia, respectively. These results highlight the power of in vitro models to investigate the dynamics of the spermatogonial niche.