Abnormal methylation of ST8SIA4 in low-motility sperm: A genome-wide identification approach

Chia-Ching Chang; Li-Chun Liu; Yu-Ting Chou; Chia-Wei Chen; Chih-Chi Guo; Chying-Chyuan Chan; Ta-Jen Lin; Ching-Hui Chen; Ming-Tzeung Chung

doi:10.1016/j.tjog.2025.02.005

Abnormal methylation of ST8SIA4 in low-motility sperm: A genome-wide identification approach

Taiwan J Obstet Gynecol. 2025 Jul;64(4):650-654. doi: 10.1016/j.tjog.2025.02.005.

Authors

Chia-Ching Chang¹, Li-Chun Liu², Yu-Ting Chou³, Chia-Wei Chen⁴, Chih-Chi Guo⁴, Chying-Chyuan Chan⁵, Ta-Jen Lin⁶, Ching-Hui Chen⁷, Ming-Tzeung Chung⁸

Affiliations

¹ Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
² Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC; Department of Obstetrics and Gynecology, Tri-Service General Hospital Songshan Branch, National Defense Medical Center, Taipei, Taiwan, ROC.
³ Department of Obstetrics and Gynecology, Taipei Medical University Shaung Ho Hospital, New Taipei City, Taiwan, ROC.
⁴ Teaching and Research Office, Tri-Service General Hospital Songshan Branch, National Defense Medical Center, Taipei, Taiwan, ROC.
⁵ Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC; Department of Obstetrics and Gynecology, Taipei City Hospital Ren-Ai Branch, Taipei, Taiwan, ROC.
⁶ MJ Health Research Foundation, Taipei, Taiwan, ROC.
⁷ Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University Hospital, Taipei, Taiwan, ROC; Nuwa Fertility Center, Taipei, Taiwan, ROC. Electronic address: kath0420@tmu.edu.tw.
⁸ Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC; Department of Obstetrics and Gynecology, Taipei Medical University Shaung Ho Hospital, New Taipei City, Taiwan, ROC; Teaching and Research Office, Tri-Service General Hospital Songshan Branch, National Defense Medical Center, Taipei, Taiwan, ROC. Electronic address: trumen.tw@yahoo.com.tw.

PMID: 40602961
DOI: 10.1016/j.tjog.2025.02.005

Abstract

Objective: To identify abnormally methylated genes associated with low motility sperm and to validate the DNA methylation level of our candidate gene ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 4 (ST8SIA4) in low-motility sperm.

Materials and methods: The MethylationEPIC Array which can measure methylation at >850,000 CpG sites and a pooled DNA strategy were used to investigate the genome-wide methylation profiles in sperm with different motility. A total of seventy semen samples, including 52 normozoospermic controls and 18 asthenozoospermic samples, were used to examine the quantitative DNA methylation level of ST8SIA4 gene.

Results: Using the gene function classification in the DAVID Bioinformatics Resources, we found that the abnormally methylated genes in the asthenozoospermia samples were predominantly associated with transcription regulation, metal binding, microtubules, meiosis, palmitate, zinc, and developmental proteins. Interestingly, these glycosyltransferase-associated genes were all hypomethylated in asthenozoospermia, except for ST8SIA4.

Conclusion: The promoter methylation level of ST8SIA4 was significantly higher in sperm samples with low motility compared with normal control samples.

Keywords: Methylation; ST8SIA4; Sperm.

MeSH terms

Adult
Asthenozoospermia* / genetics
Case-Control Studies
CpG Islands
DNA Methylation* / genetics
Genome-Wide Association Study
Humans
Male
Promoter Regions, Genetic
Sialyltransferases* / genetics
Sperm Motility* / genetics
Spermatozoa*

Substances

Sialyltransferases
CMP-N-acetylneuraminate-poly-alpha-2,8-sialosyl sialyltransferase