Ontogeny of Placental Structural Development and Expression of the Renin–Angiotensin System and 11β-HSD₂ Genes in the Rabbit

Abstract 

Common pregnancy complications are associated with impaired placental development. This study aimed to characterise the ontogeny of structural correlates of rabbit placental function, its expression of genes encoding components of the renin–angiotensin system (RAS), as well as 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD₂) mRNA since these are known to be expressed by the placenta and are associated with pregnancy complications, including preeclampsia and intrauterine programming. Placentae were collected at gestational age (GA) 14, 21 and 28 (term=32 days). Gene expression was analysed using real time PCR and placental structures were quantified via image analyses. The volume densities and volumes of trophoblast, fetal capillaries, maternal blood space, surface density and surface area of trophoblast all progressively increased, while the arithmetic mean barrier thickness of trophoblast decreased across gestation. Maternal plasma renin activity (PRA) was positively correlated with volumes of trophoblast and maternal blood space, surface density and surface area of trophoblast. Placental renin mRNA declined (↓62%; P<0.01) across gestation and was negatively correlated with maternal PRA (GA0), fetal and placental weights, placental angiotensin type 1 and 2 receptors (AT₁R and AT₂R) mRNA and volume of trophoblast. AT₁R mRNA expression was increased by 92% (P<0.001) across gestation. AT₂R mRNA expression was ∼81% (P<0.01) greater at GA14 compared to GA21. Placental 11β-HSD₂ mRNA expression was ∼74% greater (P<0.01) at GA21 than GA14, but by GA28 was similar to that at GA14. These data show that changes in placental gene expression are associated with key events in placental and fetal development, indicating that the rabbit provides a good model for investigations of pregnancy perturbations that alter the RAS or programme the fetus.

Keywords: Pregnancy, Placenta, Renin–angiotensin system, Rabbit