Extracellular Ca2+-sensing receptor expression and hormonal regulation in rat uterus during the peri-implantation period

Abstract

The extracellular Ca 21 -sensing receptor (CaR) is a member of the superfamily of G protein-coupled receptors (GPCRs). It is an important mediator of a wide range of Ca 21 -dependent physiological responses in various tissues. In reproductive tissues it has been reported to play a significant role in promoting or maintaining placentation. Meanwhile, another Ca 21 regulated gene stanniocalcin-1 (STC-1) has been documented to be involved in decidualization and uterine remodelling. The phenomenon that CaR mediates STC-1's transcription responding to extracellular calcium in fish urges us to suppose that CaR, like STC-1, may also play a role in implantation and decidualization. To resolve this conjecture, we have examined the expression and hormonal regulation of the CaR gene in rat uterus during peri-implantation period. CaR mRNA was expressed at a moderate level in the luminal epithelium of the early stage of pregnancy (from day 1 to day 3). From day 2-3 it began to be expressed more strongly in the stromal cells immediately underneath the luminal epithelium, but decreased to a basal level on day 4. From day 6 to day 9 continuously, both CaR mRNA and protein were highly expressed in the primary decidua. Expression of CaR mRNA and protein in these cells was also observed when a delayed implantation was terminated by estrogen treatment to allow the embryo implantation. In contrast, only basal level expression of the molecules was detected in the cells of animals subjected to a normal-delayed implantation or the pseudopregnant condition. Embryo transplantation experiment confirmed that CaR expression at the implantation site was induced by the implanting blastocyst. Consistent with the normal pregnant process, CaR mRNA and protein in the cells were also induced by an artificial decidualization procedure. Further experiments demonstrated that treatment of the ovariectomized rat with estrogen or/and progesterone stimulated a high level expression of CaR mRNA in the uterine epithelial and glandular epithelium. In conclusion, CaR was specifically induced during the processes of implantation and subsequent decidualization and may play a role in these processes.Reproduction (2005) 129 779-788

The extracellular calcium-sensing receptor is expressed in the cumulus–oocyte complex in mammals and modulates oocyte meiotic maturation

“…This is the first study of the expression and function of CASR at the ovarian follicle level in mammals. A previous study performed in the female mammalian reproductive tract reported that CASR is spatio-temporally expressed and localized in the mammalian uterus at early pregnancy, suggesting that it might be important for blastocyst implantation and decidualization (Xiao et al 2005). Up to now, only one previous study in the horse Functional role of CASR in mammalian oocytes (Toribio et al 2003) reported CASR mRNA expression in parathyroid chief cells cultured in vitro.…”

Stanniocalcin-1 expression in normal human endometrium and dysregulation in endometriosis

“…The STC receptor, Ca-sensing receptor (CASR), is a G-protein-coupled receptor, initially identified in bovine parathyroid cells and expressed in wide variety of tissues including ovaries and uterus in human and rodents (13-15). Its major physiologic role is believed to be maintenance of calcium homeostasis, including regulation of secretion, gene expression, cell proliferation, differentiation and apoptosis (13, 16).…”

“…CASR was found to mediate STC1 secretion in response to extracellular calcium fluctuation in fish (17). It is expressed in first trimester and term human placenta (18, 19), and is induced during implantation and decidualization in rat uterus (15). …”

The Calcium-Sensing Receptor and the Reproductive System

“…Xiao et al (2005) found CaSR mRNA expression in rat uterus (Figure 2A and Table 1). CaSR mRNA and protein appeared in the luminal epithelium on day 1 of pregnancy.…”

“…Furthermore, estrogen as well as progesterone induced the expression of CaSR protein in the uterus. The strong CaSR expression at the implantation site and decidual cells in rat uterus suggests that CaSR is of relevance for blastocyst implantation and decidualization (Xiao et al, 2005). …”