Angiogenesis in the corpus luteum of early pregnancy in the marmoset and the effects of vascular endothelial growth factor immunoneutralization on establishment of pregnancy

This study investigated vascular and molecular changes in the corpus luteum (CL) of early pregnancy in the marmoset. Ovaries were studied on Days 21 (n = 6) and 28 (n = 6) of pregnancy and compared with corpora lutea from Day 21 (late luteal) of the nonconception cycle (n = 8). Endothelial cell proliferation was measured by immunocytochemical detection of incorporated bromodeoxyuridine. Endothelial cell and pericyte area were assessed by quantitative immunocytochemistry for CD31 and alpha-smooth muscle actin, respectively. Vascular endothelial growth factor (VEGF) and its receptors, kinase insert domain-containing region (KDR) and fms-like tyrosine kinase (Fit) mRNA, were localized and quantified in in situ hybridization. In addition, the effects of immunoneutralization of VEGF on establishment and maintenance of pregnancy were investigated by administering a VEGF neutralizing antibody on Days 0-10 of the luteal phase during potentially fertile cycles (n = 10) and compared with fertile controls (n = 6). No differences in the cellular or morphological parameters were found between pregnant and structurally intact nonpregnant corpora lutea. No major differences were found in expression of VEGF, Fit, or KDR in these CL. VEGF immunoneutralization markedly suppressed plasma progesterone secretion during treatment, but pregnancy rate was not significantly reduced. Thus, a role for VEGF in early pregnancy in the marmoset remains to be established. These results show that, by the late luteal phase in the marmoset, the corpus luteum has established a mature vascular system and the molecular capacity to synthesize VEGF and its receptors. A pregnancy-induced spurt of angiogenesis or gene expression does not appear to take place; rather, maintenance of the existing vasculature is all that is required for the establishment of pregnancy.