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Comparative sperm proteomics in IVF patients with differential fertilization rates identifies FAM205A as a novel biomarker for male infertility.

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Τίτλος: Comparative sperm proteomics in IVF patients with differential fertilization rates identifies FAM205A as a novel biomarker for male infertility.
Συγγραφείς: Zhang P; Reproductive Medicine Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China.; Department of Obstetrics and Gynecology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China.; Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China., Li HM; Reproductive Medicine Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China.; Department of Obstetrics and Gynecology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China., Lu S; Reproductive Medicine Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China.; Department of Obstetrics and Gynecology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China., Fan LQ; Institute of Reproductive and Stem Cell Engineering, Central South University, Changsha 410008, China.; The Reproduction Center of Reproductive and Genetic Hospital, CITIC-XIANGYA, Changsha 410008, China., Qian H; Reproductive Medicine Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China.; Department of Obstetrics and Gynecology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China., Yin J; Reproductive Medicine Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China.; Department of Obstetrics and Gynecology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China.
Πηγή: Asian journal of andrology [Asian J Androl] 2026 Jul 01; Vol. 28 (4), pp. 454-466. Date of Electronic Publication: 2026 May 12.
Τύπος έκδοσης: Journal Article; Comparative Study
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Shanghai Materia Medica Country of Publication: China NLM ID: 100942132 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1745-7262 (Electronic) Linking ISSN: 1008682X NLM ISO Abbreviation: Asian J Androl Subsets: MEDLINE
Imprint Name(s): Publication: Shanghai : Shanghai Materia Medica
Original Publication: Beijing : Science Press
Ιατρικοί όροι (MeSH): Infertility, Male*/metabolism , Infertility, Male*/genetics , Spermatozoa*/metabolism , Fertilization in Vitro*, Biomarkers/metabolism ; Acrosome/metabolism ; Male ; Humans ; Animals ; Proteomics ; Mice ; Acrosome Reaction ; Mice, Knockout ; Adult ; Sperm Proteins ; Female
Περίληψη: This study identified family with sequence similarity 205, member A (FAM205A) as a clinically significant acrosomal protein critically implicated in male idiopathic infertility. Integrated proteomic analysis of sperm from in vitro fertilization (IVF) patients categorized by fertilization outcome ( n = 12 per group; clinical validation, n = 267) revealed a strong correlation between FAM205A expression and fertilization success (76.3% in high-expression groups vs 15.4% in low-expression groups, P < 0.05), independent of standard semen parameters. Functional analyses utilizing pooled human sperm samples ( n = 20 per group) revealed that low FAM205A expression led to a significantly decreased calcium-induced acrosome reaction response (28.9% vs 49.2% in high FAM205A expression, P < 0.01), a phenotype corroborated by anti-FAM205A antibody blockade (38.1% inhibition, P < 0.01). The clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9) genome editing system (CRISPR-Cas9)-generated knockout mice lacking Fam205a1 , which is the murine ortholog of human FAM205A, exhibited complete infertility, characterized by oligospermia, asthenozoospermia, teratozoospermia, disrupted acrosome formation, and significantly reduced sperm motility. Mechanistic studies in Fam205a1 knockout mice revealed that FAM205A deficiency induces spermatid apoptosis and impairs acrosomal exocytosis, a crucial process for sperm-egg fusion. The results demonstrate that FAM205A regulates fertility through two mechanisms: preserving structural integrity during spermiogenesis and facilitating the acrosomal reaction (AR). This study identified FAM205A as a reliable diagnostic biomarker for idiopathic male infertility and a potential treatment target in reproductive medicine.
(Copyright ©The Author(s)(2026).)
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Contributed Indexing: Keywords: FAM205A; acrosome reaction; biomarker; fertilization failure; male infertility; sperm motility
Substance Nomenclature: 0 (Biomarkers)
0 (Sperm Proteins)
Entry Date(s): Date Created: 20260512 Date Completed: 20260702 Latest Revision: 20260801
Update Code: 20260801
PubMed Central ID: PMC13423385
DOI: 10.4103/aja202580
PMID: 42116602
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1745-7262
DOI:10.4103/aja202580