A man’s body mass index might influence his sperm’s epigenome — chemical changes in DNA that determine how each gene is read — and even his children’s epigenome, although the magnitude of this effect on offspring is likely small, if it exists at all, a recent study suggests.
The study, titled, “Male obesity effects on sperm and next-generation cord blood DNA methylation,” was published in PLOS ONE.
Obesity is caused by a number of interconnected factors, including lifestyle, environment, and socioeconomic status. Genetics also play an important role in determining body weight, but genetic code alone doesn’t tell the full story.
Differences in how DNA is packaged and modified — epigenetic changes, which comprise a person’s epigenome — may also play a key role in how differences in BMI are passed from parent to offspring. The relationship between the epigenome and BMI, however, remains poorly understood.
In the new study, researchers set out to investigate whether men’s BMIs would be associated with epigenetic changes in their sperm or in their offspring.
To find out, they analyzed sperm from 294 donors undergoing in vitro fertilization. Based on BMI, one of the donors was underweight, 144 were in the normal range, 120 were “pre-obese,” and 29 were obese.
The researchers also analyzed umbilical cord blood samples of 113 offspring from 103 of the donors. The children included 10 sets of twins, and approximately even numbers of males and females.
The scientists specifically analyzed methylation, a type of epigenetic change, on several regions of DNA that are associated with imprinting — where a gene is “turned on or off” based on whether it was inherited from the male or female parent. They also looked at one region that has been linked to obesity, the HIF3A gene.
Due to limited quantities, not every region was assessed for every included sample.
In sperm, the methylation levels of an imprinted gene called MEG3 were significantly associated with BMI.
Additionally, MEG3 and HIF3A methylation was correlated with paternal BMI, but only in male children. In female children, there was a similar correlation with a different imprinted region, the gene IGF2.
“However,” the researchers wrote, “none of the correlated genes survived multiple testing adjustment.” That is, in statistical models that incorporated other factors, these differences (in both sperm and cord cells) were no longer significant, so the changes seen could be the result of random chance or due to other, possibly related, factors.
This caveat is rather substantial, and suggests that the differences noted have “only nominal significance” with regard to male BMI. Still, the researchers propose that this finding somewhat supports the idea that parental BMI can have epigenetic effects on reproductive cells and, perhaps, even on the epigenomes of offspring. However, more research will be needed to determine the merits of this idea, they said.