Decidualization Regulates the Expression of the Endometrial Chorionic Gonadotropin Receptor in the Primate1

Abstract

Chorionic gonadotropin (CG) plays an important role in establishing a receptive endometrium by directly modulating the function of both endometrial stromal and epithelial cells in the baboon. The focus of this study was to characterize changes in CG receptor (LHCGR, also known as CG-R) expression during the menstrual cycle and early pregnancy, particularly during decidualization. LHCGR was localized by using a peptide-specific antibody generated against the extracellular domain. Immunostaining was absent in any of the cell types during the proliferative phase of the cycle. In contrast, during the secretory phase, both luminal and glandular epithelial cells stained positively. Stromal staining was confined to the cells around spiral arteries (SAs) and in the basalis layer. This stromal staining pattern persisted at the implantation site between Days 18 and 25 of pregnancy and after CG infusion. However, as pregnancy progressed (Days 40 to 60), staining for LHCGR was dramatically decreased in the stromal cells. These data were confirmed by nonisotopic in situ hybridization. To confirm whether the loss of LHCGR was associated with a decidual response, stromal fibroblasts were decidualized in vitro, and cell lysates obtained after 3, 6, and 12 days of culture were analyzed by Western blotting. LHCGR protein decreased with the onset of decidualization in vitro, confirming the in vivo results. Addition of CG to decidualized cells resulted in the reinduction of LHCGR in the absence of dbcAMP. We propose that CG acting via its R on stromal cells modulates SA in preparation for pregnancy and trophoblast invasion. As pregnancy progresses, further modification of SA by migrating endovascular trophoblasts and subsequent decidualization results in the downregulation of LHCGR. This inhibition of LHCGR expression also coincides with the decrease of measurable CG in peripheral circulation.

Low-dose human chorionic gonadotropin may improve in vitro fertilization cycle outcomes in patients with low luteinizing hormone levels after gonadotropin-releasing hormone antagonist administration

“…Additionally, hCG messenger RNA (mRNA) is transcribed as early as the two-cell stage of the embryo (47), and the hCG protein is already being secreted by the embryo before implantation (48,49). Thus, there appears to be an effect of hCG on the regulation of the endometrium and on implantation (50)(51)(52)(53). The addition of LH activity in the form of hMG or recombinant LH has been associated with an increase in implantation rates (11,38,54,55), although other studies have not confirmed this finding (56,57).…”

The role of chorionic gonadotropin and Notch1 in implantation

“…Similarly, as pregnancy progresses, subsequent decidualization results in the downregulation of the LH/CG receptor, thought to be a prerequisite for the morphological transformation of stromal cells in the endometrium. This reduction in receptor expression corresponds to a decrease in CG in peripheral circulation [22].…”

“…The CG receptor is ubiquitously expressed in reproductive organs [10,11]. Targeted deletion of the CG receptor results in an altered endometrial phenotype and disrupted gene expression [12].…”

Differential effects of human chorionic gonadotropin and decidualization on insulin-like growth factors-I and -II in human endometrial stromal cells

“…Apart from the classical hormones E 2 and P, hCG has an influence on the maternal endometrium and the process of implantation (20)(21)(22)(23)(24)(25). These effects are mediated by hCG/ LH-receptors expressed in the endometrium, which show a special cycle-dependent profile of expression (26)(27)(28). We recently have been able to demonstrate that hCG reduces IGF binding protein (IGFBP)-1 in decidualized endometrial stromal cells in vivo and in vitro (23,29).…”