Paternal Folate Status and Sperm Quality, Pregnancy Outcomes, and Epigenetics: A Systematic Review and Meta-Analysis

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Abstract

Scope: The effectiveness of maternal folate in reducing the risk of congenital malformations during pregnancy is well established. However, the role of the paternal folate status is scarcely investigated. The aim of this study is to investigate the evidence of associations between the paternal folate status and sperm quality, sperm epigenome, and pregnancy outcomes. Methods and results: Databases are searched up to December 2017 resulting in 3682 articles, of which 23 are retrieved for full-text assessment. Four out of thirteen human and two out of four animal studies show positive associations between folate concentrations and sperm parameters. An additional meta-analysis of four randomized controlled trials in subfertile men shows that the sperm concentration increases (3.54 95% confidence interval (CI) [−1.40 to 8.48]) after 3–6 months of 5 mg folic acid use per day compared to controls. Moreover, two out of two animal and one out of three human studies show significant alterations in the overall methylation of the sperm epigenome. One animal and one human study show associations between low folate intake and an increased risk of congenital malformations. Conclusions: This systematic review and meta-analysis shows evidence of associations between paternal folate status and sperm quality, fertility, congenital malformations, and placental weight.

Original languageEnglish
Article number1900696
JournalMolecular Nutrition and Food Research
Volume64
Issue number9
DOIs
Publication statusPublished - 1 May 2020

Bibliographical note

Funding Information:
The authors thank Wichor M. Bramer, biomedical information specialist, Erasmus MC Rotterdam, The Netherlands, for his assistance in the systematic search and assessment of literature. This research was funded by the department of Obstetrics and Gynecology of the Erasmus Medical Center, Rotterdam.

Funding Information:
The authors thank Wichor M. Bramer, biomedical information specialist, Erasmus MC Rotterdam, The Netherlands, for his assistance in the systematic search and assessment of literature. This research was funded by the department of Obstetrics and Gynecology of the Erasmus Medical Center, Rotterdam.

Publisher Copyright:
© 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

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