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Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2022

Open Access 01-12-2022 | Infertility | Correspondence

A loss-of-function variant in SSFA2 causes male infertility with globozoospermia and failed oocyte activation

Authors: Gelin Huang, Xueguang Zhang, Guanping Yao, Lin Huang, Sixian Wu, Xiaoliang Li, Juncen Guo, Yuting Wen, Yan Wang, Lijun Shang, Na Li, Wenming Xu

Published in: Reproductive Biology and Endocrinology | Issue 1/2022

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Abstract

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 positive SSFA2 expression in the acrosome of human sperm. Liquid chromatography–mass spectrometry/mass spectrometry (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.
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Metadata
Title
A loss-of-function variant in SSFA2 causes male infertility with globozoospermia and failed oocyte activation
Authors
Gelin Huang
Xueguang Zhang
Guanping Yao
Lin Huang
Sixian Wu
Xiaoliang Li
Juncen Guo
Yuting Wen
Yan Wang
Lijun Shang
Na Li
Wenming Xu
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2022
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-022-00976-5

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