“We found that mice born to mothers who were fed a low protein diet four weeks before conception, during pregnancy and then lactation were smaller from birth. Because they grew normally, they remained smaller than mice born to mothers who had had a normal diet. What remained small were the animals’ muscles,” said Dr. Ignatia B. Van den Veyer, vice chair of research in the Department of Obstetrics and Gynecology at BCM and corresponding author of the study. “While prior studies of mothers fed this kind of diet showed that animals were predisposed to diabetes, we did not see this.”
“We think this difference occurs because we fed them the low protein diet before they conceived,” said Dr. Alfred Balasa, a postdoctoral associate in Van den Veyver’s laboratory and the USDA/ARS Children’s Nutrition Research Center at BCM and Texas Children’s Hospital.
Liver test differed
When they analyzed the animals’ gene expression at one year of age (adulthood in a mouse), they found changes of the cohesin-mediator complex in the liver. While the livers looked normal, these genes were overexpressed and some liver enzyme tests were different.
The complex of cohesin genes help in organizing and maintaining the architecture of the chromatin, the DNA and proteins that make up the contents of the nucleus of the cells. Cohesins and mediators are also known to function together in regulating when sets of genes are expressed together.
“The livers looked normal but they were functioning differently,” said Balasa.
New epigenetic mechanism?
“We started to wonder if this is a new and different epigenetic mechanism that may play a role in how the body handles exposures to poor nutrition or an otherwise suboptimal environment in early development,” said Van den Veyver.
An epigenetic mechanism is one that acts on the already formed DNA after the animal is conceived. Changes of histones, the chief protein components of the chromatin, that act as spools around which DNA winds, and DNA methylation play a role in gene regulation have already been found under similar circumstances. This new finding may add on another layer of epigenetic regulation.
“If you look at the mice, they are not less healthy,” said Balasa. “They are smaller and leaner. Some of the liver enzymes were significantly lower in the low protein offspring when compared to controls.”
He and Van den Veyver plan to study the effect of this diet and perhaps other early exposures on cohesin changes also happens in other organs of the mice.
Others who took part in this research include Dr. Amarilis Sanchez-Valle (another first author of the report), Dr. Bekim Sadikovic, Dr. Haleh Sangi-Haghpeykar, Jaclyn Bravo, Liang Chen, Dr. Wei Liu, Shu Wen and Dr. Marta L. Fiorotto, all of BCM.
Funding for this work came from the U.S. Department of Agriculture, Agriculture Research Service, the National Institute of Arthritis, Musculoskeletal and Skin Diseases and the National Institute of General Medical Sciences.
For more information on research at Baylor College of Medicine, please go to www.bcm.edu/fromthelab.