Is human chorionic gonadotropin directly involved in the regulation of human implantation?

Abstract

Please cite this article as: Licht, P., Fluhr, H., Neuwinger, J., Wallwiener, D., Wildt, L., Is human chorionic gonadotropin directly involved in the regulation of human implantation? Molecular and Cellular Endocrinology (2007), doi:10.1016/j.mce.2006 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.A c c e p t e d M a n u s c r i p t A c c e p t e d M a n u s c r i p t 2 SummaryThe regulation of human implantation is not fully understood. HCG as one of the earliest embryonal signals may be a major regulator in the parakrine embryoendometrial communication. The expression of full-length hCG/LH-receptor mRNA could be demonstrated in human endometrium throughout the follicular and secretory phase of the menstrual cycle. In contrast, in early pregnancy decidua only truncated variants could be detected. To investigate direct effects of hCG on the human endometrium, an intrauterine microdialysis device was developed to measure parakrine mediators within the uterine cavity in vivo. Using this system, hCG was applied in the secretory phase and the endometrial response was evaluated. The administration of hCG (500 IU/ml) provoked a significant inhibition of intrauterine IGFBP-1 and M-CSF, while LIF, VEGF and MMP-9 were significantly stimulated.Taken together there appear to be multiple direct effects of hCG on the endometrium that precede the classical endocrine role of the hormone.

Human endometrial milk fat globule-epidermal growth factor 8 (MFGE8) is up regulated by estradiol at the transcriptional level, and its secretion via microvesicles is stimulated by human chorionic gonadotropin (hCG)

“…hCG was shown having direct paracrine effects on the endometrium that precede its endocrine role of rescuing the corpus luteum, and regulates IGFBP-1 and prolactin in decidualized human endometrial stromal cells [51][52][53][54]. Here, hCG did not affect MFGE8 gene expression levels, consistent with previous results from our laboratory showing no change in primary human endometrial epithelial cells [31].…”

“…(protein score and mass-kD): annexin (182, 38690), actin (708, 41710-41766), glyceraldehide 3-phosphate dehydrogenase (47,36030), heat shock cognate (88, 70854), proteasome subunit alpha (52,29537), and tubulin alpha (110, 49863-50120). AFM imaging confirmed the presence of secreted membranous structures, likely microvesicles from the pellets after ultracentrifugation of the Ishikawa cells media.…”

Evidence for cross-talk between the LH receptor and LH during implantation in mice

“…According to our previous observations and those of other groups, hCG plays important paracrine roles in implantation, angiogenesis and immune tolerance (Perrier d'Hauterive et al 2004Edwards 2006;Licht et al 2007;Rao and Lei 2007). Because of Fig.…”

“…Transcription of hCG begins before implantation (Jurisicova et al 1999), as shown in a study in which the hCG production in fluid that was removed from in vitro-cultured embryos was detected as soon as 170 h after insemination (Fishel et al 1984). In addition, the results of recent studies demonstrate that hCG plays a crucial role in regulating endometrial cell differentiation and the implantation process; it not only participates in these processes via its endocrine role, but also in a paracrine manner at the maternalfetal interface (Han et al 1999;Cameo et al 2004;Afshar et al 2007;Licht et al 2007). Blastocyst hCG increases endometrial secretion of proimplantatory leukaemia inhibitory factor (LIF; Perrier d' Hauterive et al 2004) and macrophage-colony stimulating factor (M-CSF; Licht et al 2001), increases stromal COX2 (cyclo-oxygenase 2) expression (Han et al 1996) and reduces the expression of the decidual marker IGF-BP1 (insulinlike growth factor binding protein 1) during the late secretory phase (Licht et al 2002;Fluhr et al 2006).…”

Association of rs7260002 of chorionic gonadotrophin β5 with idiopathic recurrent spontaneous abortion in Chinese population

“…Low levels of hCG in the first trimester of pregnancy has long been considered as a predictor of miscarriage, ectopic pregnancy, and failure of IVF procedure [7][8][9]. Intensive studies have revealed that its function includes maintaining the production of steroid hormones and other growth factors in the corpus luteum, blastocyst implantation, uterine vascularization and angiogenesis, uterine quiescence, and immunological adaptation during pregnancy [16][17][18][19]. HCG, a glycoprotein hormone, is composed of identical alpha subunit similar to other glycoprotein hormones (LH, FSH, and TSH) in addition to a hormone-specific beta catalytic subunit [20].…”