Letter Epublish 12 citations
PubMed: 35836265 DOI: 10.1186/s12958-022-00976-5
A loss-of-function variant in SSFA2 causes male infertility with globozoospermia and failed oocyte activation.
Reprod Biol Endocrinol 20(1):103
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
Affiliations
- Department of Obstetrics/Gynecology, Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Joint Lab for Reproductive Medicine(SCU-CUHK), West China Second University Hospital, Sichuan University, Chengdu, China.
- Department of Reproductive Medicine Center, The Affiliated Hospital of Zunyi Medical University, Zunyi, China.
- Department of Reproductive Endocrinology of West China Second University Hospital, Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, Chengdu, China.
- School of Human Sciences, London Metropolitan University, London, UK.
- Laboratory of Medical Systems Biology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
- Department of Obstetrics/Gynecology, Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Joint Lab for Reproductive Medicine(SCU-CUHK), West China Second University Hospital, Sichuan University, Chengdu, China.
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.
MeSH
Genes, Acrosome, Reproduction, Infertility, Oocytes, Teratozoospermia, Therapeutics, Infertility, Male, Sperm Injections, Intracytoplasmic, Spermatozoa