Germ cell-specific deletion of Pex3 reveals essential roles of PEX3-dependent peroxisomes in spermiogenesis

J Biomed Res. 2023 Dec 8;38(1):24-36. doi: 10.7555/JBR.37.20230055.

Abstract

Peroxisomes are organelles enclosed by a single membrane and are present in various species. The abruption of peroxisomes is correlated with peroxisome biogenesis disorders and single peroxisomal enzyme deficiencies that induce diverse diseases in different organs. However, little is known about the protein compositions and corresponding roles of heterogeneous peroxisomes in various organs. Through transcriptomic and proteomic analyses, we observed heterogenous peroxisomal components among different organs, as well as between testicular somatic cells and different developmental stages of germ cells. As Pex3 is expressed in both germ cells and Sertoli cells, we generated Pex3 germ cell- and Sertoli cell-specific knockout mice. While Pex3 deletion in Sertoli cells did not affect spermatogenesis, the deletion in germ cells resulted in male sterility, manifested as the destruction of intercellular bridges between spermatids and the formation of multinucleated giant cells. Proteomic analysis of the Pex3-deleted spermatids revealed defective expressions of peroxisomal proteins and spermiogenesis-related proteins. These findings provide new insights that PEX3-dependent peroxisomes are essential for germ cells undergoing spermiogenesis, but not for Sertoli cells.

Keywords: PEX3; male infertility; oxidative stress; peroxisome; spermiogenesis.

Grants and funding

The current study was supported by grants from the National Natural Science Foundation of China (Grant No. 31890784 to J.S.), National Key R&D Program (Grant No. 2021YFC2700200 to X.G.), National Natural Science Foundation of China (Grant Nos. 92068109 and 82122025 to Yan Yuan), Natural Science Foundation of the Jiangsu Higher Education Institutions of China (Grant No. 21KJA310007 to Yan Yuan), and Science Foundation of Gusu School (Grant No. GSKY20220101 to J.S.).