The recent National Health and Nutrition Examination Survey found that one-half of pregnant women are either overweight or obese. Clinical and animal model studies have established that maternal obesity increases several health risks for both mother and infant. In pregnant women, obesity leads to increased risk for gestational diabetes, preeclampsia, and delivery complications. Maternal obesity is also associated with several fetal and neonatal complications; most significant among these are increased cases of abnormal fetal growth, premature birth, and stillbirth. Offspring of obese mothers are at an increased risk of developing several complications notably obesity, cardiovascular disease, diabetes, and asthma later in life. These observations strongly suggest that maternal obesity during pregnancy results in a dysregulation of immunity and inflammation in the offspring. This hypothesis is supported by murine studies that demonstrated worse outcomes in infection, autoimmunity, and allergic sensitization in offspring of obese dams. However, the exact nature of this dysregulation and the mechanisms underlying it remain poorly understood. In this application, we propose to investigate the impact of maternal obesity on the developing immune system by comparing composition and function of innate and adaptive immune cells from cord blood samples collected from neonates born to lean, overweight, and obese mothers. This analysis will reveal novel insights into the impact of maternal obesity during pregnancy on the development of the neonatal immune system, and will provide the foundation for future in depth studies to examine the molecular basis for these changes and their clinical implications.
Obesity during pregnancy is associated with increased morbidity and mortality for both mother and infant. The mother is at increased risk of developing gestational diabetes, preeclampsia, and cesarean delivery; whereas risks for the offspring include fetal malformations, stillbirth, and developing obesity, diabetes, and cardiovascular disease later in life. Recent studies also indicate increased risk of developing asthma, which suggest defects in the immune system of infants born to obese mothers. However, the nature of these defects remains poorly understood. This application seeks to address this gap in knowledge in order to facilitate future interventional studies to improve health outcomes in this vulnerable population.
| Sureshchandra, Suhas; Marshall, Nicole E; Wilson, Randall M et al. (2018) Inflammatory Determinants of Pregravid Obesity in Placenta and Peripheral Blood. Front Physiol 9:1089 |
| Sureshchandra, Suhas; Wilson, Randall M; Rais, Maham et al. (2017) Maternal Pregravid Obesity Remodels the DNA Methylation Landscape of Cord Blood Monocytes Disrupting Their Inflammatory Program. J Immunol 199:2729-2744 |
| Wilson, Randall M; Messaoudi, Ilhem (2015) The impact of maternal obesity during pregnancy on offspring immunity. Mol Cell Endocrinol 418 Pt 2:134-42 |
| Wilson, Randall M; Marshall, Nicole E; Jeske, Daniel R et al. (2015) Maternal obesity alters immune cell frequencies and responses in umbilical cord blood samples. Pediatr Allergy Immunol 26:344-51 |
