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Cited by 14Sperm and Testicular FunctionReproductive Biology and FertilityGenomics and Rare Diseases

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

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Huang, Gelin, Zhang, Xueguang, Yao, Guanping, Huang, Lin, Wu, Sixian, Li, Xiaoliang, Guo, Juncen, Wen, Yuting +4 more·2022·Reproductive Biology and Endocrinology
DOI 10.1186/s12958-022-00976-5PMC PMC9281110
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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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  • In some cases of globozoospermia with certain genetic mutations, sperm cannot initiate oocyte activation even after the use of ICSI.

    “In some cases of globozoospermia with certain genetic mutations, sperm cannot initiate oocyte activation even after the use of ICSI (45).”

    From Isolated teratozoospermia: revisiting its relevance in male infertility: a narrative review (2024) · cites this paper as [45]

  • A study in China on a young man with globozoospermic primary infertility found that a loss-of-function variant of the SSFA2 gene contributed to infertility due to globozoospermia and failure of oocyte activation.

    “Additionally, a study in China on a young man with globozoospermic primary infertility found that a loss-of-function variant of the SSFA2 gene contributed to infertility due to globozoospermia and failure of oocyte activation (45).”

    From Isolated teratozoospermia: revisiting its relevance in male infertility: a narrative review (2024) · cites this paper as [45]

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Cited by

Sorted by citations

Authors
Huang, G., Zhang, X., Yao, G., Huang, L., Wu, S., Li, X., Guo, J., Wen, Y., Wang, Y., Shang, L., Li, N., & Xu, W.
Affiliations
  • Sichuan University (CN)
  • Zunyi Medical University (CN)
  • London Metropolitan University (GB)
  • Guangzhou Women and Children Medical Center (CN)
Corresponding author
  • Li, Na
  • Xu, Wenming
ORCID
Venue
Reproductive Biology and Endocrinology
Publisher
Springer Science and Business Media LLC
Published
2022-07-14
Volume
20
Issue
1
Pages
103-103
ISSN
1477-7827 (ISSN-L)
DOI
10.1186/s12958-022-00976-5
PMC
PMC9281110
OpenAlex
W4285390482
Cited by
14
References
1
Citations by year
2026: 3 · 2025: 2 · 2024: 6 · 2023: 3
FWCI
2.32
Type
journal article
Language
en
Open access
Licence
Locations
  • Reproductive Biology and Endocrinology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • London Met Repository (London Metropolitan University) (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
National Key Research and Development Program of China (2018YFC1003603)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
Keywords
globozoospermia, male infertility, teratozoospermia, loss-of-function mutations, acrosome formation, artificial oocyte activation, intracytoplasmic sperm injection, GSTM3, actin, genetic diagnosis
MeSH terms
Teratozoospermia, Chromatography, Liquid, Humans, Infertility, Male, Male, Oocytes, Semen, Spermatozoa, Tandem Mass Spectrometry

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