Maternal Protein Deficiency During Pregnancy ‘Memorized’ by Fetal Muscle Cells

22 Sep 2015 --- A new study has uncovered the genetic processes that link insufficient protein consumption during pregnancy with the development of muscle problems in mothers and their male offspring. The findings also shed light on the metabolic pathway through which these genetic changes are transferred to the fetus, potentially triggering the development of chronic health problems in adulthood such as cardiovascular disease, obesity and Type 2 diabetes, according to researchers at the University of Illinois.

Detecting biomarkers of protein insufficiency during the early stages of pregnancy could enable clinicians to treat it through dietary changes or other strategies, possibly averting many serious health conditions in the next generation, said Huan Wang, the principal investigator on the study, published in the British Journal of Nutrition.

Although Wang’s study involved rats, prior research has shown that the implications are similar for humans. During pregnancy, women require at least an additional 25 grams of protein per day. Inadequate protein consumption by pregnant women has been linked to their children developing various chronic health problems as adults.

Wang found that inadequate protein intake during pregnancy activates the amino acid response (AAR) pathway, triggering cell destruction – a process called autophagy – as well as atrophy, or wasting, of the mother’s skeletal muscles. Autophagy is a survival mechanism whereby cells under stress conditions degrade unnecessary or dysfunctional components to maintain homeostasis in the body.

These genetic changes may be transferred through the placenta and “memorized” in the skeletal muscles of the fetus, causing low birth weight and stunted growth in male offspring, the research team reported in the study.

Wang says; “this research identifies the mechanism behind the thrifty phenotype hypothesis. Our model, low protein diet during pregnancy mimics the nutrient starvation which matches the thrifty phenotype model. This is the link we’ve been seeking for years, which shows transduction from the mom through the placenta to the child. However, the cell autophagy is activated in the skeletal muscles of the male offspring only, so there is gender specificity. Apparently the female offspring have more resistance to low-protein exposure during gestation and to cell autophagy.”

In Wang’s study, pregnant rats in the low-protein group consumed food that contained 8 or 9 percent protein, while those in the control group consumed about twice as much – 18 to 20 percent protein. After giving birth, all of the rats consumed the control diet during lactation, as did all of their pups after weaning. The rats’ body weights and food intake were recorded every other day.

The mother rats on the low-protein diet gained significantly less weight during pregnancy, and their pups were smaller at birth, Wang found. The low-protein diet also changed the levels of key amino acids in the mothers’ blood plasma. At the end of pregnancy, mothers in the low-protein group had lower levels certain amino acids and higher levels of others, suggesting potential disturbances in their protein metabolism, according to the study.

Insufficient protein intake also increased the activation of several AAR pathway downstream genes in both the mothers’ and their male pups’ skeletal muscles. However, their other tissues – and those of the female pups – were unaffected.

Follow-up data indicated that the AAR- and autophagy-related genes remained activated in the skeletal muscles of the male pups, suggesting that the amino acid limitation signal within the pregnant mothers’ skeletal muscles was transferred to the placenta and then to their offspring, according to the study.

The findings underscore the importance of women consuming healthy diets with adequate amounts of protein during pregnancy to protect the health of their children, from birth through adulthood, said Wang, currently a postdoctoral researcher in human genetics at the University of California at Los Angeles.

The Dietary Reference Intake for protein is 0.8 grams of protein per kilogram of body weight per day for the average sedentary non-pregnant woman and 1.1 grams per kilogram of body weight per day for pregnant women.

Wang’s co-authors on the paper were U. of I. faculty members Yuan-Xiang Pan and Donald K. Layman, both in food science; and Stéphane Lezmi, nutritional sciences. Illinois alumni Xiuwen Chen, Gabriel J. Wilson and Dan Zhou also were co-authors on the paper.