Nor1 and Mitophagy: An Insight into Sertoli Cell Function Regulating Spermatogenesis Using a Transgenic Rat Model.

Area of Science:

• Reproductive Biology
• Molecular Endocrinology
• Cellular Biology

Background:

• Male infertility affects global health, with many idiopathic cases.
• Sertoli cells (Scs) are vital for germ cell (Gc) development and male fertility.
• The role of mitophagy-related genes in Sc differentiation and male fertility remains unclear.

Purpose of the Study:

• To investigate the role of mitophagy-related genes in Sc differentiation.
• To identify novel genes regulating male fertility through Sc function.
• To explore the function of Neuron-derived orphan receptor 1 (Nor1) in male reproduction.

Main Methods:

• Analysis of microarray dataset GSE48795 to identify mitophagy-related hub genes.
• Generation of a transgenic rat model with Sc-specific knockdown of Nor1 during puberty.
• Functional analysis of spermatogenesis and fertility in transgenic rats.

Main Results:

• Identified 12 mitophagy-related hub genes, including Bcl2 and Fos.
• Nor1 was identified as a potential mitophagy-related gene associated with Sc maturation.
• Sc-specific knockdown of Nor1 resulted in impaired spermatogenesis and reduced male fertility.

Conclusions:

• Nor1 plays a significant role in regulating Sertoli cell function.
• Nor1 is a key mitophagy-related gene essential for maintaining male fertility.
• Targeting Nor1 may offer therapeutic strategies for male infertility.