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High paternal homocysteine causes ventricular septal defects in mouse offspring.

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.

SUBMITTER: Liu L

PROVIDER: S-EPMC10960133 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

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High paternal homocysteine causes ventricular septal defects in mouse offspring.

Liu Lian L Zhang Xuan X Geng Hao-Ran HR Qiao Ya-Nan YN Gui Yong-Hao YH Zhao Jian-Yuan JY

iScience 20240307 4

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- ...[more]

PMID: 38523790

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Project description:ObjectivesThis study aimed at assessing the association between maternal methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) gene polymorphisms, maternal dietary habits, and their interactions with the risk of ventricular septal defects (VSD) in offspring.MethodsFrom November 2017 to March 2019, a case-control study comprising 360 mothers of VSD cases and 504 mothers of healthy infants was conducted in Han Chinese populations. The main exposures of interest were maternal dietary habits in early pregnancy and MTHFD1 gene polymorphisms. Logistic regression models were used to estimate the main effects and interaction effects.ResultsIt was observed that maternal excessive intake of pickled vegetables (aOR = 1.85, 95%CI: 1.45-2.37), smoked foods (aOR = 1.93, 95%CI: 1.48-2.51), barbecued foods (aOR = 1.74, 95%CI: 1.28-2.36), and fried foods (aOR = 1.68, 95%CI: 1.30-2.17) were associated with a higher risk of VSD in offspring, whereas maternal excessive intake of fresh meat (aOR = 0.61, 95%CI: 0.47-0.79), fish and shrimp (aOR = 0.29, 95%CI: 0.23-0.38), fresh eggs (aOR = 0.54, 95%CI: 0.42-0.70), fresh fruits or vegetables (aOR = 0.44, 95%CI: 0.33-0.60), soy foods (aOR = 0.65, 95%CI: 0.53-0.80), and milk products (aOR = 0.49, 95%CI: 0.40-0.59) could contribute significantly to a lower risk of VSD in offspring. Furthermore, the genetic polymorphisms of maternal MTHFD1 gene at rs1950902 (GA vs. GG: aOR = 0.67, 95%CI: 0.50-0.90) and rs2236222 (GG vs. AA: aOR = 2.75, 95%CI: 1.57-4.83) were significantly associated with the risk of VSD in offspring. In addition, there was a significant interaction effect between maternal dietary habits and MTHFD1 gene polymorphisms on the risk of VSD.ConclusionsMaternal dietary factors, MTHFD1 genetic polymorphisms, and their interactions were all associated with the risk of VSD in offspring. However, further research in diverse ethnic populations and with a larger sample size is warranted to corroborate our findings.Trial registrationRegistered in Chinese Clinical Trial Registry Center; registration number, ChiCTR1800016635; registration date, 06/14/2018 (Retrospectively registered); URL of trial registry record, https://www.chictr.org.cn/showproj.aspx?proj=28300.

Dataset Information

High paternal homocysteine causes ventricular septal defects in mouse offspring.

Publications

High paternal homocysteine causes ventricular septal defects in mouse offspring.

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