Pregnancy

Placental Growth Throughout the Last Two Thirds of Pregnancy in Sheep: Vascular Development and Angiogenic Factor Expression

Abstract
Morphometric methodologies were developed and applied to investigate the pattern of vascular development in the maternal (caruncular; CAR) and fetal (cotyledonary; COT) sheep placenta throughout the last two-thirds of gestation. We also examined expression of the major angiogenic factors and their receptors in CAR and COT. Although vascularity of the CAR tissues increased continuously from day 50 through 140 of pregnancy, those of COT tissues increased at about twice the instantaneous rate (i.e., the proportionate increase/day) of the CAR. For CAR, vascularity increased two-fold from day 50 through 140 via relatively small increases in capillary number and two- to three-fold increases in capillary diameter. For COT, the increased vascularity resulted from a 12-fold increase in capillary number associated with a coincident two-fold decrease in capillary diameter. This large increase in the fetal placental capillary number, due to increased branching, resulted in a (6-fold) increase in total capillary cross-sectional area and total capillary surface, per unit of COT tissue. Different patterns of mRNA expression of the angiogenic factors and their receptors were shown in CAR and COT by using quantitative RT-PCR. The "dilation-like" angiogenesis of CAR was correlated with vascular endothelial growth factor receptor 1 (FLT1), angiopoietin 2 (ANGPT2), and soluble guanylate cyclase (GUCY1B3) mRNA expression. The "branching-like" angiogenesis of COT was correlated with vascular endothelial growth factor (VEGF), FLT1, angiopoietin 1 (ANGPT1), ANGPT2 and FGF2 mRNA expression. Monitoring the expression of angiogenic factors and correlating it with quantitative measures of vascularity gives us the ability to model angiogenesis in a spatiotemporal fashion.

Key words: Growth factors • Placenta • Uterus

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