Understanding the effects of maternal undernutrition in early gestation on placental development in late gestation
Chronic diseases such as cardiovascular disease and diabetes are on the rise among the U.S. population. Heart Disease is the leading cause of death in the US and is responsible 610,000 deaths per year. A suite of risk factors for cardiovascular disease and diabetes – obesity, elevated blood sugar,hypertension, excess cholesterol, and elevated triglycerides, referred to asMetabolic Syndrome, contributes to an increased risk of mortality. These too areincreasingly prevalent. For example, according to the CDC, in 2011 more than 35% of the U.S. population was obese, with a financial burden of US $147 billion annually. Though improper diet, lack of exercise and socioeconomic status areassociated with these adult diseases, inadequate maternal nutrition just prior toor during pregnancy is also a risk factor. The goal of my research is to identifythe critical time point by which maternal under-nutrition (MUN) during earlygestation permanently alters placental development, the mechanism by whichthis occurs, and whether leptin acts as a mediator.The relationship between the maternal environment and long-term healthof offspring is referred to as the developmental origins of health and disease (DOHaD), or sometimes fetal programming. MUN during pregnancy may affectdeveloping organs to alter the phenotypic outcome of the offspring to promoteadult disease. The timing of the insult is also critical. During the periconceptionalperiod and early gestation, there are major developmental processes such asembryonic organogenesis, and placenta formation. There are also two rounds of DNA methylation reprogramming that occur. I investigated the effects of maternalunder-nutrition from three weeks prior to gestation to d 11.5 (mid gestation inmice). I found that maternal periconceptional food restriction until mid- gestationaffected formation of blood spaces within the labyrinthine placenta near term, ascompared to those from control-fed dams. There was also a three-fold decreasein mRNA encoding SNAT4, an amino acid transporter, in restricted placentae.These changes in placentae from dams fed a nutrient restricted diet suggestsome compensation to ensure adequate nutrients are available to the fetus forproper development.I also examined the effects MUN undernutrition during the first half ofgestation had on placental DNA methylation at late gestation and whether leptinwould act as a mediator of these effects. It is not entirely understood howinformation about maternal nutrition is sensed by the placenta. Leptin, is ahormone that is secreted by fat tissue and plays a role in energy homeostasis,metabolism and reproduction. Therefore, it could be one potential mechanism bywhich maternal nutrition can influence placental function and in turn, fetaldevelopment. I found placentae from dams who experienced MUN and leptinsupplementation had a greater number of differentially methylated regionscompared to placentae from dams fed an adequate fed diet than did placentae ofdams fed MUN only. Regions that were differentially methylated by maternal dietand/or leptin supplementation were located near genes in pathways involved inmolecular transport and carbohydrate metabolism as well as postnatal growth,weight and body size, formation of new blood vessels during embryogenesis. These pathways suggest a link between maternal food deprivation andoffspring's' growth, metabolism and formation of the cardiovascular system.
Van Gronigen Case, Gerialisa Allison Marcella
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