NOR1 and Mitophagy: An Insight into Sertoli Cell Function Regulating Spermatogenesis

Abstract

The development and differentiation of germ cell (Gc) is supported by the Sertoli cel (Sc). We previously reported that a developmental switch in Sc around 12 days of age onwards in rats. During the process of differentiation of Sc, the differential expression of mitophagy-related genes and its role in male fertility is poorly understood. To address this gap, we evaluated the microarray dataset GSE48795 to identify 12 mitophagy-related hub genes - Egfr, Bcl2, Ccl2, Mmp2, Igf1, Fgf7, Apoe, Fos, Cxcl12, Ocln, Dcn, and Snca. We identify NOR1 as a potential mitophagy-related gene of interest due to its strong regulatory association with two hub genes Bcl2 and Fos. To determine the importance of our analysis of finding key mitophagy-related genes, we generated a transgenic rat model with Sc-specific knockdown of NOR1 during puberty. Adult male transgenic rats were found to be infertile due to impaired spermatogenesis, indicating a critical role for NOR1 in Sc function. These findings suggest that mitophagy-related genes may play an important role in the differentiation of Sc and thereby, regulate male fertility.