Associations between fetal size, sex and placental angiogenesis in the pig(†)

Inadequate fetal growth cannot be remedied postnatally, leading to severe consequences for neonatal and adult development. It is hypothesized that growth restriction occurs due to inadequate placental vascularization. This study investigated the relationship between porcine fetal size, sex, and placental angiogenesis at multiple gestational days (GD). Placental samples supplying the lightest and closest to mean litter weight (CTMLW), male and female Large White X Landrace fetuses were obtained at GD30, 45, 60, and 90. Immunohistochemistry revealed increased chorioallantoic membrane CD31 staining in placentas supplying the lightest compared to those supplying the CTMLW fetuses at GD60. At GD90, placentas supplying the lightest fetuses had decreased CD31 staining in the chorioallantoic membrane compared to those supplying the CTMLW fetuses. The mRNA expression of six candidate genes with central roles at the feto-maternal interface increased with advancing gestation. At GD60, ACP5 expression was increased in placentas supplying the lightest compared to the CTMLW fetuses. At GD45, CD31 expression was decreased in placentas supplying the lightest compared to the CTMLW fetuses. In contrast, CD31 expression was increased in placentas supplying the lightest compared the CTMLW fetuses at GD60. In vitro endothelial cell branching assays demonstrated that placentas supplying the lightest and male fetuses impaired endothelial cell branching compared to placentas from the CTMLW (GD45 and 60) and female fetuses (GD60), respectively. This study has highlighted that placentas supplying the lightest and male fetuses have impaired angiogenesis. Importantly, the relationship between fetal size, sex, and placental vascularity is dynamic and dependent upon the GD investigated.