Ovch2, also known as ovochymase 2, is an epididymis-specific trypsin-like serine protease. It plays a crucial role in sperm maturation, a process essential for male fertility. Ovch2 is part of the NELL2-ROS1-OVCH2-ADAM3 lumicrine signaling system, where it is required for processing the sperm surface protein ADAM3, which is necessary for sperm fertilizing ability [1].

In gene-modified mouse models, deletion of Ovch2 disrupts the proteome of epididymal sperm. This leads to decreased levels of core fertility-related factors like ADAM3, β-defensins, and protease-inhibitor complexes. However, it also causes compensatory upregulation of alternate proteases and chaperones. Additionally, the absence of CUB domains in Ovch2, which are unique to this protein, does not significantly affect male fertility under normal housing conditions, suggesting that the protease domain of Ovch2 is more critical for sperm processing [2,3].

In conclusion, Ovch2 is a key regulator of sperm maturation in the mammalian epididymis. Studies using KO mouse models have revealed its essential role in male fertility by modulating proteolytic pathways during sperm maturation. Understanding Ovch2's function provides a framework for developing strategies to address idiopathic male infertility and enhance male contraceptive design [3].

References:

1. Kiyozumi, Daiji, Noda, Taichi, Yamaguchi, Ryo, Matzuk, Martin M, Ikawa, Masahito. . NELL2-mediated lumicrine signaling through OVCH2 is required for male fertility. In Science (New York, N.Y.), 368, 1132-1135. doi:10.1126/science.aay5134. https://pubmed.ncbi.nlm.nih.gov/32499443/

2. Kent, Katarzyna, Nozawa, Kaori, Sutton, Courtney, Garcia, Thomas X, Matzuk, Martin M. 2023. CUB domains are not required for OVCH2 function in sperm maturation in the mouse epididymis. In Andrology, 12, 682-697. doi:10.1111/andr.13508. https://pubmed.ncbi.nlm.nih.gov/37551853/

3. Kent, Katarzyna, Nozawa, Kaori, Jain, Antrix, Garcia, Thomas X, Matzuk, Martin M. 2025. Ovochymase 2 is a key regulatory factor modulating proteolytic pathways and sperm maturation in the mammalian epididymis. In Biology of reproduction, , . doi:10.1093/biolre/ioaf069. https://pubmed.ncbi.nlm.nih.gov/40155198/