USP9Y, the ubiquitin-specific protease 9 gene on the Y chromosome, is a functional homologue to USP9X on the X chromosome. It encodes a ubiquitin-specific protease with a core promoter region, and both mouse and human genes are under selective constraint to maintain their amino acid sequences, indicating an important function [2]. USP9Y may play a role in male germ cell development through de-ubiquitination, potentially stabilizing a target protein crucial for this process [3].

Whole-genome sequencing identified USP9Y as a potential candidate gene associated with non-obstructive azoospermia, suggesting a role in spermatogenesis [1]. However, a normospermic man with a complete deletion of USP9Y was reported, indicating it may not have a key role in male reproduction [4]. Also, natural transmission of USP9Y gene mutations in two families led to a mild testicular phenotype, suggesting it is more of a fine-tuner in spermatogenesis rather than an essential function provider [5].

In conclusion, while USP9Y has been implicated in male germ cell development and spermatogenesis, its exact role remains somewhat unclear. Findings from studies on individuals with USP9Y deletions or mutations have provided a new perspective on its function in male fertility, showing that it may not be as essential as previously thought for sperm maturation and fertilizing ability.

References:

1. Malcher, Agnieszka, Stokowy, Tomasz, Berman, Andrea, Yatsenko, Alexander N, Kurpisz, Maciej K. 2022. Whole-genome sequencing identifies new candidate genes for nonobstructive azoospermia. In Andrology, 10, 1605-1624. doi:10.1111/andr.13269. https://pubmed.ncbi.nlm.nih.gov/36017582/

2. Hall, Nicola M, Brown, Graeme M, Furlong, Robert A, Rocha, Dominique, Affara, Nabeel A. . Usp9y (ubiquitin-specific protease 9 gene on the Y) is associated with a functional promoter and encodes an intact open reading frame homologous to Usp9x that is under selective constraint. In Mammalian genome : official journal of the International Mammalian Genome Society, 14, 437-47. doi:. https://pubmed.ncbi.nlm.nih.gov/12925892/

3. Lee, Kyung Ho, Song, Gyun Jee, Kang, Inn Soo, Chung, Chin Ha, Rhee, Kunsoo. . Ubiquitin-specific protease activity of USP9Y, a male infertility gene on the Y chromosome. In Reproduction, fertility, and development, 15, 129-33. doi:. https://pubmed.ncbi.nlm.nih.gov/12895410/

4. Luddi, Alice, Margollicci, Maria, Gambera, Laura, Balestri, Paolo, Piomboni, Paola. . Spermatogenesis in a man with complete deletion of USP9Y. In The New England journal of medicine, 360, 881-5. doi:10.1056/NEJMoa0806218. https://pubmed.ncbi.nlm.nih.gov/19246359/

5. Krausz, Csilla, Degl'Innocenti, Selene, Nuti, Francesca, Varriale, Gennaro, Forti, Gianni. 2006. Natural transmission of USP9Y gene mutations: a new perspective on the role of AZFa genes in male fertility. In Human molecular genetics, 15, 2673-81. doi:. https://pubmed.ncbi.nlm.nih.gov/16893908/