Obesity of Pregnant Women May Affect Future Generations

    If mom tips the weight scales, she may also tip her offspring, and subsequent generations, toward metabolic dysfunction. And mom’s influence may be conveyed through the maternal germline, which means that future generations could consume healthy diets and still be predisposed to obesity-related conditions such as type 2 Diabetes and heart disease.

    New research shows that a woman’s obesity can cause genetic abnormalities that are passed through the female bloodline to at least three subsequent generations, increasing the risk of obesity-related conditions. This finding comes from a mouse study that was conducted at Washington University School of Medicine in St. Louis, where scientists fed female mice a high-fat, high-sugar diet from before conception until weaning and then followed the outcomes in the next three generations of offspring, all fed a control diet.

    From 6 weeks prior to conception until weaning, the scientists fed mice a high-fat, high-sugar diet comprised of about 60% fat and 20% sugar. “This mimics more of the Western diet,” said Kelle H. Moley, M.D., the School of Medicine’s James P. Crane Professor of Obstetrics and Gynecology. “Basically, it’s like eating fast food every day.”

    The results of a study led by Dr. Moley appeared June 16 in the journal Cell Reports, in an article entitled, “Maternal Metabolic Syndrome Programs Mitochondrial Dysfunction via Germline Changes across Three Generations.”

    “We found that, despite consuming a normal diet, the first, second, and third generations of female offspring developed mitochondrial dysfunction and abnormal mitochondrial morphology in their skeletal muscle,” wrote the article’s authors. “Moreover, the mitochondrial dynamic proteins DRP-1 and OPA1 were misexpressed in the skeletal muscles of F1, F2, and F3 mice, suggesting an imbalance of fission and fusion. Mitochondrial abnormalities were also present in the germ cells of F1 and F2 females, suggesting that transmission of the mitochondrial phenotype occurred through the maternal germline.”

    More research is needed to determine if a consistent diet low in fat and sugar, as well as regular exercise, may reverse genetic metabolic abnormalities.

    “It’s important to note that in humans, in which the diets of children closely mirror those of their parents, the effects of maternal metabolic syndrome may be greater than in our mouse model,” Dr. Moley noted. “In any case, eating nutritiously is critical.”

    “Research, including this study, points to poor maternal nutrition and a predisposition to obesity,” Dr. Morely continued. “Our findings indicate that a mother’s obesity can impair the health of later generations. This is particularly important because more than two-thirds of reproductive-age women in the United States are overweight or obese.”

    In the current study, Dr. Morely and colleagues considered the possibility tha tearly-life exposure to maternal obesity affects the epigenome. There is already evidence that changes to the nuclear epigenome may promote metabolic disease in offspring. In addition, there could be changes to mtDNA. Such changes, which are inherited through the maternal germline, may provide a mechanism for transmission of metabolic dysfunction.

    “Although we did not examine the epigenetic mechanisms leading to inheritance of abnormal mitochondrial phenotypes,” wrote the authors, “our data showing altered mitochondrial metabolism, morphology, and OPA1 expression in offspring germ cells suggest that both modification of nuclear-encoded mitochondrial genes and altered mtDNA play a role.”