Trophoblast invasion and blood vessel remodeling are altered in a rat model of lifelong maternal obesity.

Maternal obesity is associated with an increased risk of a number of pregnancy complications, including fetal demise, which may be linked to impaired placental development as a result of altered trophoblast invasion and vessel remodeling. Therefore, we examined these parameters in pregnant rats fed a control (normal weight) or high fat (HF) diet (obese) at 2 critical times of rat placental development. Early trophoblast invasion was increased by approximately 2-fold in HF-fed dams with a concomitant increase in the expression of matrix metalloproteinase 9 protein, a mediator of tissue remodeling and invasion. Furthermore, we observed significantly higher levels of smooth muscle actin surrounding the placental spiral arteries of HF-fed dams, suggesting impaired spiral artery remodeling. Taken together, the results of this study suggest that altered placental development is an important contributor to the poor pregnancy outcomes and increased fetal demise in our model of lifelong maternal obesity.

Adverse fetal and neonatal outcomes associated with a life-long high fat diet: role of altered development of the placental vasculature.

Maternal obesity results in a number of obstetrical and fetal complications with both immediate and long-term consequences. The increased prevalence of obesity has resulted in increasing numbers of women of reproductive age in this high-risk group. Since many of these obese women have been subjected to hypercaloric diets from early childhood we have developed a rodent model of life-long maternal obesity to more clearly understand the mechanisms that contribute to adverse pregnancy outcomes in obese women. Female Sprague Dawley rats were fed a control diet (CON--16% of calories from fat) or high fat diet (HF--45% of calories from fat) from 3 to 19 weeks of age. Prior to pregnancy HF-fed dams exhibited significant increases in body fat, serum leptin and triglycerides. A subset of dams was sacrificed at gestational day 15 to evaluate fetal and placental development. The remaining animals were allowed to deliver normally. HF-fed dams exhibited a more than 3-fold increase in fetal death and decreased neonatal survival. These outcomes were associated with altered vascular development in the placenta, as well as increased hypoxia in the labyrinth. We propose that the altered placental vasculature may result in reduced oxygenation of the fetal tissues contributing to premature demise and poor neonatal survival.