Language
English
Publication Date
7-13-2025
Journal
Biology of Reproduction
DOI
10.1093/biolre/ioaf069
PMID
40155198
PMCID
PMC12260502
PubMedCentral® Posted Date
3-28-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Spermatozoa acquire fertilizing competence during epididymal transit through proteolytic, chaperone-mediated, and post-translational modifications. Ovochymase 2, an epididymis-specific trypsin-like serine protease, has emerged as a central regulator of this maturation process. Here, we integrate targeted gene disruption, comprehensive proteomic profiling, and affinity-based proteome enrichment to delineate how Ovochymase 2 influences sperm functionality. Deletion of Ovochymase 2 disrupts the proteome of epididymal sperm, resulting in diminished levels of core fertility-related factors-including a disintegrin and metalloprotease domain 3, β-defensins, and protease-inhibitor complexes-while inducing compensatory upregulation of alternate proteases and chaperones. Interaction assays confirm direct or indirect associations between Ovochymase 2 and sperm surface proteins critical for fertilization, highlighting its essential protease domain and the transient, and finely regulated nature of its substrates. Collectively, these findings position Ovochymase 2 as an orchestrator of sperm surface remodeling, with broad implications for fertility diagnostics and therapeutic interventions. By revealing a multifaceted network of Ovochymase 2-dependent pathways, this study provides a mechanistic framework for developing innovative strategies to counter idiopathic male infertility and to enhance male contraceptive design.
Keywords
Male, Epididymis, Animals, Sperm Maturation, Mice, Proteolysis, Spermatozoa
Published Open-Access
yes
Recommended Citation
Kent, Katarzyna; Nozawa, Kaori; Jain, Antrix; et al., "Ovochymase 2 Is a Key Regulatory Factor Modulating Proteolytic Pathways and Sperm Maturation in the Mammalian Epididymis" (2025). Faculty, Staff and Students Publications. 6540.
https://digitalcommons.library.tmc.edu/baylor_docs/6540