Expression and Production of Human Chorionic Gonadotropin (hCG) in the Normal Secretory Endometrium: Evidence of CGB7 and/or CGB6 Beta hCG Subunit Gene Expression1

Abstract

We have previously confirmed glandular cell CGB and CGA subunit mRNA gene expression as well as the expression of their dimeric and single-subunit human chorionic gonadotropin (hCG) proteins in normal secretory transformed endometrium. The objective of this study was to investigate the endometrial epithelial gene locus of the human hCG/LH gene cluster from CGB genes responsible for gene expression. For this study, endometrial specimens were selected from women characterized using our endometrium score and hCG staining index that had normal secretory transformed endometrium and optimal hCG staining. Using full-length CGB mRNA sequence analysis, we found that epithelial CGB is (co)expressed as the product of gene locus CGB7 and CGB6 (48%), as single CGB7 (42%), or to a lower percentage as single CGB6 (10%). In addition to known differences between these genes and CGB5, the nucleotide sequence of the mRNA differs between CGB7 and CGB6 in the untranslated promoter region and in translated exon 2. Immunohistochemical results show that endometrial joint CGB7 and CGB6, single CGB7, and single CGB6 mRNA expression lead to the release of endometrial hCG. Genespecific antibodies for CGB7 reveal secretory endometrial hCG production, which is not observed for gene-specific CGB5 antibodies, whereas the placenta is positive for CGB5 and negative for CGB7 antibody as revealed by immunohistochemistry and Western blot hCG isoform analysis. Only endometrial CGB7 expression seems to be supported specifically by secretory endometrial transcription factors. In conclusion, epithelial hCG is expressed and produced as CGB7 and/or CGB6 but not CGB5, and it is produced together with CGA as a secretory transformation marker in the normal secretory phase endometrium.endometrium, female reproduction tract, human chorionic gonadotropin (hCG/hCG receptor), menstrual cycle, uterus

Luteinizing hormone and human chorionic gonadotropin: distinguishing unique physiologic roles

“…The role of hCG in fostering endometrial receptivity appears to begin even before embryonic hCG expression. It has been shown that epithelial hCG is expressed and produced in human endometrium biopsy specimens during the early to mid-secretory phase of the menstrual cycle [44]. Elucidating the precise role of hCG in endometrial functions related to implantation remains an active subject of investigation.…”

Transcriptome Analysis Reveals New Insights into the Modulation of Endometrial Stromal Cell Receptive Phenotype by Embryo-Derived Signals Interleukin-1 and Human Chorionic Gonadotropin: Possible Involvement in Early Embryo Implantation

“…Following implantation, hCG is produced by syncytiotrophoblast of the developing conceptus [11]. Recent evidence suggests that hCG is also produced in glandular and luminal epithelium of human endometrium, primarily during the secretory phase [12], [13]. hCG production by embryonic cells may directly regulate the expression of endometrial factors and extend the period during which the endometrium is receptive [2], [14].…”

Increased maternal hCG concentrations in early in vitro pregnancy with elevated basal FSH

“…In addition, we also found that maternal BMI and the number of oocytes retrieved were negatively associated with hCG concentrations on Day 14 and Day 21. A previous study demonstrated that increased maternal BMI in early pregnancy reduces serum hCG concentrations [ 22 ]. Crude linear regression demonstrated that hCG concentrations also decrease during the retrieval of a high number of oocytes during IVF-ET [ 3 ].…”