240. Reduced endometrial angiogenesis during early pregnancy in relaxin-deficient mice

Abstract

Relaxin is a peptide hormone with important roles in the reproductive tract, including the growth and remodelling of endometrial vasculature. It has been shown to stimulate VEGF secretion from human endometrial stromal cells in vitro and increases endometrial vascularisation in ovariectomised steroid-primed primates in vivo. We have used mouse models to show that oestrogen and progesterone stimulate angiogenesis (new blood vessel growth) within the endometrium. Endometrial angiogenesis also occurs in the early stages of mouse pregnancy, which coincides with an increase in circulating progesterone. To date, no studies have investigated the effects of relaxin on endometrial angiogenesis in early pregnancy. Our aim was to test the hypothesis that endometrial angiogenesis would be reduced in relaxin-deficient mice (Rln^−/−) in comparison to their wildtype (Rln^+/+) counterparts. Uterine tissues were collected from Rln^−/− and Rln^+/+ mice on days 1 to 4 of pregnancy, before implantation. All mice were treated with BrdU before dissection to allow the number of blood vessel profiles containing proliferating endothelial cells (PVPs) to be quantified by double CD31/BrdU immunohistochemistry. Consistent with published studies, PVPs were first observed on days 3 and 4 of pregnancy. However, the percentage of PVPs was reduced in Rln^−/− mice compared with Rln^+/+ mice (Day 3: median = 4.4% v. 19.6%, Day 4: 9.6% v. 22.2%). We subsequently identified relaxin and relaxin receptors in the mouse endometrium in early pregnancy. Our data suggest that locally synthesised relaxin acts in synergy with progesterone to initiate endometrial angiogenesis in early pregnancy.