Effects of uteroplacental restriction on the relaxin-family receptors, Lgr7 and Lgr8, in the uterus of late pregnant rats

Abstract

The peptide hormone relaxin stimulates uterine growth and endometrial angiogenesis and inhibits myometrial contractions in a variety of species. The receptor for relaxin is a leucine-rich repeat containing G-protein-coupled receptor Lgr7 (RXFP1) that is highly expressed in the myometrium of late pregnant mice, with a significant decrease in receptor density observed at term. The present study first compared the expression of Lgr7 with another relaxin-family receptor Lgr8 (RXFP2) in the uterus and placenta of late pregnant rats. The uterus was separated into endometrial and myometrial components, and the myometrium into fetal and non-fetal sites, for further analysis. We then assessed the response of these receptors to uteroplacental restriction (UPR). Expression of the Lgr7 gene was significantly higher in the uterus compared with the placenta. Within the uterus, on Day 20 of gestation, there was equivalent expression of Lgr7 in fetal and non-fetal sites of the myometrium, as well as in the endometrium v. myometrium. The second receptor investigated, Lgr8, was also expressed in the endometrium and myometrium, but at significantly lower levels than Lgr7. Bilateral ligation of the maternal uterine blood vessels on Day 18 of gestation resulted in uteroplacental restriction, a decrease in fetal weight and litter size, and a significant upregulation in uterine, but not placental, Lgr7 and Lgr8 gene expression in UPR animals compared with controls. These data suggest that both relaxin family receptors are upregulated in response to a reduction in uteroplacental blood flow in rats.