503 - Alterations of placental gene expression in obese pregnant mice

Poster Number: 503
Publication Number: 503.238

Hui Zhao, Stanford University School of Medicine, Stanford, CA, United States; Ronald J. Wong, Stanford University School of Medicine, Stanford, CA, United States; David K. Stevenson, Stanford University School of Medicine, Stanford, CA, United States

Background: Maternal obesity (body mass index [BMI] ≥ 30) is a risk factor for many pregnancy complications, including miscarriages, gestational hypertension, preeclampsia, gestational diabetes, preterm births, stillbirths, intrauterine growth restriction (IUGR), macrosomia, etc. The greatest risk is found in women who are obese before conceiving and gain significant weight during pregnancy. In addition, obesity is associated with placental lipo-toxicity, oxidative stress, and inflammation.

Objective: Here we aim to investigate how high-fat diet (HFD)-induced obesity affects placental gene expression and development.

Design/Methods: To induce obesity, adult female FVB mice were fed a HFD (60 kcal% fat) while control mice were given a low-fat diet (LFD, 10 kcal% fat). Two feeding schedules were applied: (1) a HFD during mating and throughout pregnancy (HFD pregnancy); and (2) a HFD initiated 4 weeks prior to mating and during pregnancy (HFD pre-conception). Maternal weights were monitored daily. Glucose levels in blood collected from tails or by cardiac puncture were measured using a glucometer. At different gestational ages (E7.5, E8.5, E9.5, E11.5, and E16.5), placentas were collected for total RNA isolation. Gene expression levels were then quantified using custom-designed PCR arrays and compared between all groups.

Results: Significant maternal weight gain was found in mice on both feeding schedules compared with pregnant LFD controls. However, glucose levels in the HFD and LFD groups were not significantly different. Expression levels of several placental genes were significantly different in both HFD groups compared with LFD controls. Specifically, HIF1A, HO-1, SOD-1, VEGFA, Angpt1, IL-6, AP2, Nrf2 were downregulated and Gpx1 was upregulated. Although this trend was similar for both HFD groups, it was more dramatic in the HFD preconception group.Conclusion(s): A HFD can induce gestational obesity in mice, and subsequently affect the expression of placental genes that are associated with oxygen sensing, oxidative stress, angiogenesis, and inflammation. Preconceptional obesity can aggravate these alterations and therefore may heighten the risk for pregnancy complications.