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Oxidative stress in sperm affects the epigenetic reprogramming in early embryonic development
Sarah Wyck1,2,3, Carolina Herrera1, Cristina E Requena4,5
1Clinic of Reproductive Medicine, Department for Farm Animals, University of Zurich, 8057, Zurich, Switzerland.
Epigenetics & Chromatin
|October 19, 2018
Summary
Oxidative stress in sperm damages DNA and impairs epigenetic reprogramming, negatively affecting early embryo development. This study reveals how sperm DNA lesions impact embryonic genome activation and DNA demethylation in cattle.
Area of Science:
- Reproductive Biology
- Epigenetics
- Developmental Biology
Background:
- Oxidative stress from reactive oxygen species (ROS) is a key factor in male infertility.
- Sperm are vulnerable to ROS-induced DNA damage due to limited repair capabilities.
- The impact of sperm oxidative DNA lesions on early embryonic development is not well understood.
Purpose of the Study:
- To investigate the effects of sperm oxidative stress on early embryonic development using cattle as a model.
- To determine how oxidative DNA lesions in sperm influence embryonic genome activation and epigenetic reprogramming.
Main Methods:
- Fertilization with sperm exposed to oxidative stress.
- Analysis of embryonic developmental arrest at genome activation.
- Measurement of DNA damage response markers (e.g., γH2AX, XRCC1 recruitment).
- Quantitative immunofluorescence and LC-MS to assess DNA demethylation and 5-hydroxymethylcytosine (5hmC) levels.
Main Results:
- Sperm oxidative stress caused developmental arrest during embryonic genome activation.
- DNA damage response levels did not directly correlate with developmental defects.
- Maternal base excision repair (BER) machinery repaired some sperm DNA lesions.
- Oxidative DNA lesions in sperm impaired zygotic active DNA demethylation in a 5hmC-independent manner.
Conclusions:
- Sperm oxidative stress impacts both DNA integrity and epigenetic reprogramming, affecting the paternal contribution to embryo development.
- Impaired DNA demethylation due to sperm DNA lesions can harm embryo development and quality.
- Significant differences exist in DNA methylation dynamics between bovine and mouse zygotes.
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