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Sperm Imprinted Gene Methylation and DNA Fragmentation in ICSI Outcomes: A Pilot Study.
Anna Chiara Conflitti1, Fani Konstantinidou2,3, Alessandra Buonacquisto1
1Laboratory of Seminology and Sperm Bank "L. Gandini", Department of Experimental Medicine, "Sapienza" University of Rome, 00161 Rome, Italy.
Epigenomes
|May 27, 2026
Summary
Sperm DNA fragmentation and methylation of H19, IGF2, and PEG1/MEST impact intracytoplasmic sperm injection outcomes. Lower sperm DNA fragmentation and specific methylation patterns correlate with viable embryo development, suggesting these epigenetic markers influence fertility.
Area of Science:
- Reproductive Biology
- Epigenetics
- Sperm Biology
Background:
- Aberrant DNA methylation of imprinted genes and increased sperm DNA fragmentation (SDF) are linked to male infertility.
- The precise impact of these factors on assisted reproductive technology (ART) outcomes, such as intracytoplasmic sperm injection (ICSI), requires further investigation.
Purpose of the Study:
- To investigate the relationship between SDF and the methylation status of imprinted genes H19, IGF2, and PEG1/MEST.
- To determine the influence of these sperm molecular and epigenetic features on fertilization and embryo development following ICSI.
Main Methods:
- Semen analysis was performed according to WHO 2021 guidelines.
- Sperm DNA fragmentation (SDF) was assessed using the TUNEL assay.
- DNA methylation analysis of H19, IGF2, and PEG1/MEST was conducted using pyrosequencing on sperm samples from men undergoing ICSI.
Main Results:
- Sperm DNA fragmentation was significantly lower in the group with viable embryos compared to other groups.
- Positive correlations were observed between H19 and IGF2 methylation and viable embryo development.
- Total PEG1/MEST methylation positively correlated with fertilization events and viable embryo formation.
Conclusions:
- Sperm DNA fragmentation and methylation levels of H19, IGF2, and PEG1/MEST are associated with ICSI success rates.
- These findings suggest that sperm molecular and epigenetic characteristics play a role in influencing fertilization and embryo development.
- Sperm epigenetic markers may serve as potential indicators for predicting ART outcomes.
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