{"doi":"10.1093/biolre/ioaf069","title":"Ovochymase 2 is a key regulatory factor modulating proteolytic pathways and sperm maturation in the mammalian epididymis","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.","journal":"Biology of Reproduction","year":2025,"id":531262,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9576,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":275901,"name":"Kaori Nozawa","orcid":"0000-0002-2256-278X","position":1,"is_corresponding":false},{"id":255488,"name":"Antrix Jain","orcid":"0000-0002-2815-3645","position":2,"is_corresponding":false},{"id":57598,"name":"Anna Malovannaya","orcid":"0000-0003-2953-6485","position":3,"is_corresponding":false},{"id":275908,"name":"Thomas X. Garcia","orcid":"0000-0001-7761-2660","position":4,"is_corresponding":false},{"id":275907,"name":"Martin M. Matzuk","orcid":"0000-0002-1445-8632","position":5,"is_corresponding":false},{"id":275900,"name":"Katarzyna Kent","orcid":"0000-0002-4528-3425","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:51:14.579161Z","pmid":"40155198","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}