IGF2, IGF binding protein 1, and matrix metalloproteinases 2 and 9 in implantation-stage endometrium following immunoneutralization of vascular endothelial growth factor in the rhesus monkey

Abstract

Blastocyst implantation in the rhesus monkey is inhibited by administration of antibody against vascular endothelial growth factor (VEGF) A during peri-implantation period with no change in the circulatory concentrations of estradiol, progesterone, and VEGF. In this study, we have investigated the effect of administration of a MAB to VEGFA on days 5 and 10 after ovulation upon the mRNA expression, immunopositive protein expression, and immunohistological localization of IGF2, IGF binding protein 1 (IGFBP1) and matrix metalloproteinases (MMPs) 2 and 9 in the implantation-stage endometrium collected on day 13 after ovulation from fecund cycles of rhesus monkeys. The comparison between isotype-matched IgG (control; n=8)- and VEGF antibody (VEGF Mab; n=8)-treated animals revealed higher (P<0.05) IGF2 in lacunar and villous syncytiotrophoblasts, trophoblast cell columns, migrating extravillous trophoblast cells, and endovascular trophoblast cells in control animals, but with no change in the various cell types of maternal endometrium between the two groups. No change in IGFBP1 expression in the endometrium was observed between the two groups. MMPs 2 and 9 were detected in syncytiotrophoblast in lacunae and villi, trophoblast cell columns, and extravillous trophoblast cells in control samples. MMP9 transcript expression in maternal endometrium and its immunopositivity in endometrial stroma and trophoblast cells were lower (P<0.05) with no change in MMP2 level in VEGF Mab-exposed samples compared with those in control samples. A functional network involving VEGF, IGF2, and MMP9 in early placental trophoblast cells and maternal endometrium appears to be important for normal placentation.