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Huang, Gelin, Zhang, Xueguang, Yao, Guanping, Huang, Lin, Wu, Sixian, Li, Xiaoliang, Guo, Juncen, Wen, Yuting, Wang, Yan, Shang, Lijun, Li, Na and Xu, Wenming (2022) A loss-of-function variant in SSFA2 causes male infertility with globozoospermia and failed oocyte activation. Reproductive Biology and Endocrinology, 20 (103). pp. 1-13. ISSN 1477-7827
Globozoospermia (OMIM: 102530) is a rare type of teratozoospermia (< 0.1%). The etiology of globozoospermia is complicated and has not been fully revealed. Here, we report an infertile patient with globozoospermia. Variational analysis revealed a homozygous missense variant in the SSFA2 gene (NM_001130445.3: c.3671G > A; p.R1224Q) in the patient. This variant significantly reduced the protein expression of SSFA2. Immunofluorescence staining showed posi- tive SSFA2 expression in the acrosome of human sperm. Liquid chromatography–mass spectrometry/mass spectrom- etry (LC–MS/MS) and Coimmunoprecipitation (Co-IP) analyses identified that GSTM3 and Actin interact with SSFA2.
Further investigation revealed that for the patient, regular intracytoplasmic sperm injection (ICSI) treatment had a poor prognosis. However, Artificial oocyte activation (AOA) by a calcium ionophore (A23187) after ICSI successfully rescued the oocyte activation failure for the patient with the SSFA2 variant, and the couple achieved a live birth. This study revealed that SSFA2 plays an important role in acrosome formation, and the homozygous c.3671G > A loss-of-function variant in SSFA2 caused globozoospermia. SSFA2 may represent a new gene in the genetic diagnosis of globozoospermia, especially the successful outcome of AOA-ICSI treatment for couples, which has potential value for clinicians in their treatment regimen selections.
Available under License Creative Commons Attribution 4.0.
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