Date of this Version
Obesity is an epidemic in many developed nations and maternal obesity can result in developmental alterations in offspring that have long-lasting effects. Two experiments were conducted to determine the impact of maternal obesity on placental development and early embryonic growth and muscle development. Experiment one utilized obese Lethal Yellow (LY) and normal weight C57BL/6 (B6) dams to assess how maternal obesity alters skeletal muscle development in mid-gestational embryos. Embryos from LY dams exhibited decreased embryo and placental weights as well as an increase in the myogenic marker desmin. Furthermore, the adipogenic marker PPARG expression was predominately localized to the neural tube and was significantly decreased in LY-derived embryos. The objective of experiment 2 was to identify how maternal obesity alters placenta development and function and may be associated with altered development of the fetus. The same mid-gestation embryos and corresponding placenta from LY and B6 dams were used. Placenta from LY dams were smaller than when developed in a B6 dam and exhibited a phenotype of reduced function. The placenta also displayed increased hypoxia markers and decreased gene expression of enzymes which regulate the transfer of active glucocorticoids from the mother to developing embryo. Interestingly, the embryos reared in an obese dam possessed decreased expression of vasculature markers. In summary, these experiments support the following findings: (1) maternal obesity decreases embryonic and placental weight and results in altered temporal regulation of myogenesis; (2) PPARG expression is localized to the neural tube and decreased in LY-derived embryos indicating a function for this transcription factor in neural tube development and suggesting that obesity alters this function; (3) placenta from an obese dam display increased hypoxemia and altered glucocorticoid metabolism resulting in altered embryonic vasculature and potentially differences in the function of various organ systems. These data represent an important shift in understanding how maternal obesity reduces skeletal muscle density during development and its long-term effects on the metabolic health of their children.
Advisor: Jennifer R. Wood