Regulation of the spermatogonial niche factor GDNF by retinoic acid

The aim of this thesis was to clarify the mechanism behind RA-mediated GDNF regulation, which is a crucial factor, secreted by Sertoli cells, for spermatogonial stem cells self-renewal. We demonstrated that RA negatively regulates GDNF in murine Sertoli cells. RARα is the nuclear receptor involved in this regulation acting through a novel-identified Retinoic Acid Responsive Element (RARE) on Gdnf murine promoter. Data obtained with HDACi and ChIP-qPCR suggested that Gdnf promoter undergoes a de-acetylation after RA treatment. Regarding human testis, we found that in our culture conditions testis tissue positively responds to RA stimulation while RA effect on gdnf expression is heterogeneous. Our results can ameliorate the comprehension of the spermatogonial stem cell niche in its physiological conditions but also in relation to the increasing cases of male infertility.