Epitranscriptomic modifications in embryonic development: insights into natural and ART-induced mechanisms and
Alessandro M Volsa1, Eva R Hoffmann2, Pablo J Ross3
1Department of Physiology, International Excellence Campus for Higher Education and Research (Campus Mare Nostrum), University of Murcia, Murcia, Spain.
Human Reproduction Update
|December 25, 2025
Summary
Assisted reproductive technologies (ART) can disrupt crucial RNA modifications in embryos, impacting development and health. Understanding epitranscriptomic regulation is key to improving ART safety and efficacy for better reproductive outcomes.
Area of Science:
- Reproductive Biology
- Epigenetics
- Developmental Biology
Background:
- Mammalian embryo development relies on complex molecular regulation.
- Assisted reproductive technologies (ART) are widely used globally for human and animal fertility.
- Epitranscriptomic marks, like N6-methyladenosine (m6A), regulate gene expression during development, but ART's impact is unclear.
Purpose of the Study:
- To review the role of epitranscriptomic modifications in naturally conceived and ART-conceived embryos.
- To examine how RNA modifications influence gametogenesis and early embryonic development.
- To explore how ART-induced stress may affect these regulatory layers and offspring health.
Main Methods:
- Searched PubMed and Scopus for peer-reviewed articles and reviews.
- Used keywords: 'epitranscriptomic', 'RNA modification', 'gametogenesis', 'embryo development', 'ART'.
- Critically evaluated and discussed relevant publications up to the current year.
Main Results:
- Epitranscriptomic modifications, especially m6A, are key regulators of RNA metabolism in gametogenesis and early embryo development.
- ART stressors (oxidative imbalance, hormonal stimulation, cryopreservation) can disturb RNA methylation (m1A, 5-methylcytosine).
- These alterations affect embryo competence, placental function, lineage specification, and offspring development, highlighting epitranscriptomic marks as biomarkers and targets.
Conclusions:
- Understanding ART's influence on the epitranscriptome is crucial for improving reproductive outcomes.
- In vitro procedures can negatively impact RNA regulation in gametes and embryos, leading to implantation failure and pregnancy loss.
- Insights into epitranscriptomic modifications guide safer and more effective ART practices.
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