Decreased Expression of the Rat Myometrial Relaxin Receptor (RXFP1) in Late Pregnancy Is Partially Mediated by the Presence of the Conceptus1

Abstract

The actions of relaxin are mediated by relaxin family peptide receptor 1 (Rxfp1). In pregnant mice, myometrial Rxfp1 expression decreases at term, coinciding with the highest level of circulating relaxin. This down-regulation in Rxfp1 in reproductive tissues has not been investigated in other pregnant animals, nor are the regulatory mechanisms known. In the present study, we examined Rxfp1 gene and protein expression in the nonpregnant, pregnant, and postpartum rat uterus. The potential effects of local conceptus-derived factors on Rxfp1 expression were then examined in unilaterally pregnant rats. Immunoreactive RXFP1 was predominantly detected in the circular smooth muscle layer in the myometrium and in the decidualized endometrium. Rxfp1 was expressed in the rat myometrium from early to midgestation at levels similar to those in nonpregnant rat myometrium, with a significant reduction in expression at both the transcriptional and translational levels during late gestation. In unilaterally pregnant rats, myometrial Rxfp1 was higher in the nongravid compared to the gravid uterine horn, demonstrating a local negative influence of the fetal-placental unit on Rxfp1 expression. In summary, the down-regulation in myometrial Rxfp1 expression at the end of gestation in the rat is partially mediated by the fetal-placental unit and is indicative of a functional withdrawal of relaxin. This may represent a novel mechanism for the activation of spontaneous uterine contractions at labor in this species.

The molecular detection of relaxin and its receptor RXFP1 in reproductive tissue of Felis catus and Lynx pardinus during pregnancy

“…In rats, RXFP1 was expressed in the myometrium from early to mid-gestation at levels similar to those determined in nonpregnant rat myometrium, followed by a significant reduction during late gestation. This downregulation in myometrial RXFP1 expression at the end of gestation is indicative of a functional withdrawal of relaxin and may represent a novel mechanism for the activation of spontaneous uterine contractions at labor (Vodstrcil et al 2010). As our study did not include late pregnancy, decreasing levels of RXFP1 could not be shown for cats.…”

Progesterone Withdrawal, and Not Increased Circulating Relaxin, Mediates the Decrease in Myometrial Relaxin Receptor (RXFP1) Expression in Late Gestation in Rats1

“…These actions of relaxin are now known to be mediated through a leucine-rich repeat containing heterotrimeric guanine nucleotide-binding, G protein-coupled receptor, known as relaxin family peptide receptor 1 (RXFP1). We demonstrated significant decreases in myometrial Rxfp1 gene and protein expression in late gestation and during spontaneous labor in the rat and proposed that the RXFP1 receptor down-regulation is a mechanism of functional relaxin withdrawal necessary for the activation of CAPs in the myometrium [6].…”

“…Plasma was collected, frozen, and stored at À808C for steroid assay. The uteri were removed immediately after the animal was killed, and the decidualized endometrium and fetal-placental units were removed from the uterine wall as described previously [6]. The myometrium was then snap-frozen in liquid nitrogen and stored at À808C until RNA extraction.…”

“…First-strand cDNA synthesis used 1 lg of total RNA in a 20-ll reaction, with random hexamers (50 ng/ll) and 200 U of SuperScript III (Invitrogen). Relative quantification of Rxfp1 gene expression used the comparative cycle threshold (DDC T ) method with ribosomal Rn18s as the reference gene as previously described [6,17]. We also measured Esr1, Esr2, and Vegf mRNA expression.…”

“…In the rat, the late gestation decrease in myometrial Rxfp1 is partially mediated by the presence of the fetal-placental unit [6]. However, it also coincides with the decline in circulating progesterone levels and with the highest plasma relaxin concentrations [7].…”