The effect of lifelong maternal obesity on pregnancy outcomes and placental development

Abstract

<p>Maternal obesity is associated with an increased risk of pregnancy complications, including preeclampsia, miscarriage, birth of small for gestational age (SGA) babies, and stillbirth. Placental dysfunction has been implicated in all of these complications; however, the mechanisms by which maternal obesity influences placental development and function are not well understood. Female Sprague-Dawley rats were fed either a control diet (CON; 16% kcal from fat) or a high fat diet (HF; 45% kcal from fat) for 16 weeks beginning at weaning and were then mated with age-matched CON-fed males. This model emulates life-long obesity prior to pregnancy, a situation which is clinically relevant. Prior to pregnancy, HF-fed dams were 36% heavier and had significantly more abdominal fat. Dams were sacrificed at either gestational day (GD) 15 or GD18 to collect placental tissues. The remaining females were allowed to give birth naturally. HF-fed dams showed evidence of increased intrauterine death at GD15 and GD18. At birth, smaller litter sizes, offspring with reduced birthweight, and more stillbirths were observed in the HF-fed group. Placentas from HF-fed dams exhibited morphological changes at GD15, including an increased area covered by the labyrinth zone, an increase in blood vessel density and decrease in blood vessel maturity in the labyrinth layer, as well as increased carbonic anhydrase staining, indicative of hypoxia. These changes were associated with increased vascular endothelial growth factor (VEGF) protein levels and decreased placental growth factor (PlGF) protein levels. Both interstitial and endovascular trophoblast invasion into the maternal mesometrial triangles were increased at GD15. While these differences were no longer evident by GD18, placental morphometry demonstrated that the area covered by the labyrinth layer remained significantly greater in the HF-fed compared to CON-fed dams. Placental oxidative stress, which is often associated with placental dysfunction, was not observed at statistically significant levels at GD15. The early dysregulation of placental structure in HF-fed dams, which is normalized later in gestation, may play a role in the development of pregnancy complications associated with maternal obesity.</p>