Should Men Take Folic Acid Prior to Conception?

The need for folic acid or folate in women of childbearing age is well-known. Yet, recent research has shown that a deficiency in folic acid in male mice results in birth defects of the spine and skull.

Researchers from Canada's McGill University have discovered how epigenetic changes in sperm can transmit information to the embryo by non-DNA means. These alterations to the gene expression in sperm were caused by dietary changes, researchers found.

It is known that is mainly DNA that leads to the genetic determination of whether offspring have a predisposition to contract certain diseases. However, ongoing research is showing that in reality, DNA is only part of heredity. Simultaneously, other issues such as lifestyle, diet or obesity in parents could also directly influence their children prior to birth.

This growing study area means that new avenues of disease prevention could be explored, especially in relation to the transmission of environmental conditions from the father.

Published in Development Cell, the McGill researchers studied how environmental factors may effect sperm by feeding male mice a folate-deficient diet and following the effects this had on molecules in proteins associated with DNA.

The researchers discovered that the modified diet changed particular molecules called methyl groups. These molecules are associated with histone proteins that play an important role in packaging DNA into cells. It was discovered that these changes were passed on at fertilisation and remained throughout the development of the embryo, resulting in congenital birth defects of the spine and skull.

The authors of the study believe that the big breakthrough with this study is that it has identified a non-DNA based means by which sperm remember a father's environment (diet) and transmit that information to the embryo. It presents a major shift from what is known about heritability and disease from being solely DNA-based, to one that now includes sperm proteins.

Identification of the mechanism that is immediately altered by environmental factors such as diet, lifestyle or the impact of stress to parents may lead to the discovery of new methods for disease prevention.

This research particularly highlights that it isn't only important for women who are trying for a baby to monitor their diet, health and stress… but that it is equally important for men too, as such factors can be passed onto their offspring via their sperm. Men, alongside women, should be supplementing their diet with folic acid, prior to fertilisation.

The researchers now aim to determine if these harmful changes induced in the sperm proteins (histones) can be repaired, hoping that this work will lead to new avenues for disease prevention which will lead to healthier children and adults.

Future research investigating how information is passed from sperm to embryos will continue to shed new light on how the lifestyle of parents prior to conception is equally important for the health of their future offspring.

References:

Lismer A, et al (2021). Histone H3 lysine 4 trimethylation in sperm is transmitted to the embryo and associated with diet-induced phenotypes in the offspring. Developmental Cell (2021). Volume 56, ISSUE 5, P671-686.e6, March 08. Available at: https://doi.org/10.1016/j.devcel.2021.01.01

How sperm remember. McGill University News. Available at: https://www.mcgill.ca/newsroom/channels/news/how-sperm-remember-329649