(P11-033-23) The Impact of Gestational Diabetes and Excess Folic Acid Supplementation on Placental Development

Objectives: The relationship between excess folic acid supplementation and the risk of developing gestational diabetes (GDM) is unclear with recent observational studies reporting both an increased or a decreased risk. Women at risk for neural tube defect-affected pregnancies, including those with obesity (BMI≥30 kg/m²), are recommended to supplement with up to 10x the normal folic acid recommendations (0.4 mg/day). However, the impact of folic acid supplementation on the pathophysiology of GDM is poorly understood. The objective of my research is to determine if excess folic acid supplementation and GDM interact to impact placental development.

Methods: Female C57BL/6J mice were fed a control (10% kcal fat) (CD) or Western (45% kcal fat) (WD) diet with (10 mg/kg diet) or without (2 mg/kg diet) supplemental folic acid from weaning for 13 weeks before mating with male mice fed the unsupplemented CD. The WD was used to induce a glucose-intolerant phenotype. At gestational day 18.5, 1 male and 1 female placenta/dam were collected. H&E staining was used to assess general placental morphology and quantification of labyrinth CD31 expression by fluorescent immunohistochemistry was used to assess labyrinth vascularization.

Results: H&E staining identified deceased labyrinth and increased junctional zone area in male placenta from WD-dams compared to those from CD-dams (p < 0.05). Decreased labyrinth and increased junctional zone area was also observed in male placenta from supplemented dams compared to unsupplemented dams (p < 0.01). In males, fluorescent immunohistochemistry identified a marginally non-significant interaction between WD and supplementation whereby supplementation reduced labyrinth vascularization in male placenta from WD-dams, but not CD-dams (p=0.081). There were no effects of supplementation or WD on placental morphology or labyrinth vascularization in female placenta.

Conclusions: These findings demonstrate sex-specific impacts of maternal excess folic acid supplementation and GDM on placental development. In male offspring, these maternal factors impact placental morphological development and labyrinth vascularization, but in female offspring, there was no impact of these maternal factors on placental development.

Funding Sources: This research is funded by the Canadian Institutes of Health Research.