Baylor College of Medicine News

Not just moms: Males also play role in epigenetic change

Most studies that look at the fetal origins of metabolic syndrome (a condition that includes obesity, diabetes and heart disease) focus on the diets of mothers before and immediately after birth.

In a new study in the American Journal of Obstetrics and Gynecology, Dr. Kjersti Aagaard, associate professor of obstetrics and gynecology at Baylor College of Medicine, and Dr. Melissa Suter, an instructor in her laboratory, find that there can be a paternal component to such changes.

They and their colleagues fed a group of normal female mice a high fat diet two weeks before mating as well as through breast feeding. For comparison, they fed a similar group of mice a normal diet for the same period. The mothers mated with males who carried only one copy instead of two of one gene (Glut4). Having only one copy of the gene predisposed them to develop metabolic syndrome. The resulting mice had either two copies of the gene (normal) or only one copy (predisposed to metabolic syndrome).  

When they tested the resulting infant mice at birth and five weeks later, they found that the high fat diet to which the infant mice were exposed in the womb and soon after birth led to changes in the way fetal liver histones (the proteins that help package DNA) operate. The differences were there, whether the baby mice had one or two copies of the Glut4 gene. Some the changes persist as long as 5 weeks, said Suter.

“More than 200 genes underwent this epigenetic marking,” said Aagaard. (Epigenetic means additions to the genome that can turn genes on or off or govern the level of expression.)

“When we looked at the wild type versus the Glut 4 mice, it showed that the dad’s contribution along with that of the mom changed the fetal epigenome,” said Suter.

“This is really a good model system to look at Dad’s contribution,” said Aagaard.

“We are finding innovative ways to understand genetic susceptibility, which can, to a large extent, dictate what epigenetic variations can and cannot occur. We are looking at the attributable risk of an exposure in utero versus the additional contribution of the genomic variations and the exposure itself,” she said.

Others who took part in this research include Jun Ma and Alan Harris,of Baylor; Patricia M. Vuguin, Kirsten Hartil, Ariana Fiallo and Maureen Charron, all of Albert Einstein College of Medicine in New York.

Funding for this work came from the National Institutes of Health (Grant R01 DK089201 4, Grant NIH DP2O D001500-01, NIH REACH IRACDA K12 GM084897, NIH 5 R21 DK081194, Diabetes Research and Training Center (NIH Grant P60 DK020541, and the American Diabetes Association.