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Published on: November 22, 2013
High paternal homocysteine causes ventricular septal defects in mouse offspring
Lian Liu1, Xuan Zhang1, Hao-Ran Geng2,3
1Children's Hospital of Fudan University and Shanghai Genitourinary Cancer Institute Fudan University, Department of Urology, Fudan University Shanghai Cancer Center, Shanghai 201102, China.
Insights
High homocysteine in fathers is linked to congenital heart defects in offspring. Folic acid supplementation in fathers may reduce the risk of ventricular septal defects (VSD).
Area of Science:
- Reproductive biology
- Developmental biology
- Genetics
Background:
- Maternal hyperhomocysteinemia is a known risk factor for congenital heart disease (CHD).
- The impact of paternal homocysteine levels on offspring CHD risk is not well understood.
Purpose of the Study:
- To investigate whether elevated paternal homocysteine levels contribute to congenital heart disease in offspring.
- To explore the underlying mechanisms and potential interventions.
Main Methods:
- Male mice with increased homocysteine levels were used to assess effects on sperm and offspring.
- DNA methylation patterns in sperm and offspring were analyzed.
- The impact of folic acid supplementation was evaluated.
Main Results:
- Increased paternal homocysteine led to reduced sperm count and motility defects.
- Offspring exhibited ventricular septal defects (VSD).
- Paternal hyperhomocysteinemia altered DNA methylation in sperm and CHD-related genes.
- Folic acid supplementation reduced VSD occurrence in offspring of high-homocysteine males.
Conclusions:
- Elevated paternal homocysteine is a risk factor for VSD in offspring.
- Paternal homocysteine affects sperm epigenetics, influencing offspring development.
- Reducing paternal homocysteine may be a viable strategy for CHD prevention.
Abstract:
Maternal hyperhomocysteinemia is widely considered as an independent risk of congenital heart disease (CHD). However, whether high paternal homocysteine causes CHD remains unknown. Here, we showed that increased homocysteine levels of male mice caused decreased sperm count, sperm motility defect and ventricular septal defect of the offspring. Moreover, high levels of paternal homocysteine decrease sperm DNMT3A/3B, accompanied with changes in DNA methylation levels in the promoter regions of CHD-related genes. Folic acid supplement could decrease the occurrence of VSD in high homocysteine male mice. This study reveals that increased paternal homocysteine level increases VSD risk in the offspring, indicating that decreasing paternal homocysteine may be an intervening target of CHD.
