Chorionic gonadotrophin-β mRNA, a trophoblast marker, is expressed in human 8-cell embryos derived from tripronucleate zygotes

Bonduelle, M.; Dodd, Robert H.; Liebaers, Inge; Steirteghem, A. Van; Williamson, R.; Akhurst, Rosemary J.

doi:10.1093/oxfordjournals.humrep.a136808

Cited by 148 publications

(70 citation statements)

References 9 publications

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“…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].…”

Section: Discussionsupporting

confidence: 91%

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)

Sarhan¹,

Bocca²,

Yu³

et al. 2013

Cell Signal Traffic

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Objective: We have recently showed that MFGE8, a novel epithelial cell protein in the human endometrium, upregulated during the window of implantation. We hypothesized that MFGE8 may act as a key modulator of endometrial remodeling and trophoblast invasion. The aims of this study were (i) to investigate the in vitro regulation of human endometrial epithelial cells MFGE8 transcription, translation, and secretion by sex steroids and hCG; and (ii) to examine the possibility of MFGE8 secretion via microvesicles. Design: Experimental in vitro study using Ishikawa cells. Setting: University center. Interventions: Treatment with estradiol (E2), progesterone (P4), and human chorionic gonatropin (hCG). Main outcome measures: MFGE8 mRNA and protein expression, and identification of secreted microvesicles by mass spectrometry (MS) and immunoblotting. Results: E 2 , but not P4 or hCG, significantly upregulated MFGE8 mRNA expression. hCG significantly increased MFGE8 secretion. Microvesicels obtained after ultracentrifugation were visualized with atomic force microscopy ranging from ~100 to 200 nm. In addition to the expected 46 kD protein, the microvesicles contained a second form of secreted MFGE8 measuring ~30 kD which was confirmed by MS. Conclusions: We demonstrated (i) dual effects of E 2 and hCG on the regulation of MFGE8, and (ii) MFGE8 protein secretion in association with microvesicles. MFGE8 has the potential to modulate endometrial function and implantation via exocrine and/ or paracrine-autocrine effects. To the best of our knowledge, this is the first demonstration of microvesicular secretion of any regulatory protein by endometrial epithelial cells, providing initial evidence suggestive of microvesicular participation in cellular trafficking information in the non-pregnant and pregnant endometrium.

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Section: Discussionsupporting

confidence: 91%

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)

Sarhan¹,

Bocca²,

Yu³

et al. 2013

Cell Signal Traffic

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“…In contrast, ␤-hCG7 encodes a protein differing in three amino acids and is expressed at low levels in normal nonmalignant tissues (20,22,23). During pregnancy hCG is initially produced by the blastocyst 6 -8 days after fertilization (24,25) and later by the syncytiotrophoblast (26). The level of hCG increases during the first trimester of pregnancy and decreases to 10% of the peak value during the second and third trimesters (27).…”

Section: Cd25mentioning

confidence: 99%

Human Chorionic Gonadotropin Attracts Regulatory T Cells into the Fetal-Maternal Interface during Early Human Pregnancy

Schumacher

Brachwitz

Sohr

et al. 2009

The Journal of Immunology

278

218

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Regulatory T cells (Treg) expand during pregnancy and are present at the fetal-maternal interface at very early stages in pregnancy. The migration mechanisms of Treg to the pregnant uterus are still unclear. Human chorionic gonadotropin (hCG) is secreted by the blastocyst immediately after fertilization and has chemoattractant properties. Therefore, we sought to analyze whether hCG secreted by early trophoblasts attracts Treg to the uterus and hence contributes to maternal tolerance toward the fetus. Decidua and placenta tissue samples from patients having spontaneous abortions or ectopic pregnancies were employed to evaluate Treg and hCG levels. Age-matched samples from normal pregnant women served as controls. We further performed in vitro studies with primary first trimester trophoblast cells and a choriocarcinoma cell line (JEG-3) aiming to evaluate the ability of secreted hCG to attract Treg. Patients having miscarriages or ectopic pregnancy presented significantly decreased hCG mRNA and protein levels associated with decreased Foxp3, neuropilin-1, IL-10, and TGF-β mRNA levels as compared with normal pregnant women. Using migration assays we demonstrated that Treg were attracted by hCG-producing trophoblasts or choriocarcinoma cells. Treg migration toward cells transfected with hCG expression vectors confirmed the chemoattractant ability of hCG. Our data clearly show that hCG produced by trophoblasts attracts Treg to the fetal-maternal interface. High hCG levels at very early pregnancy stages ensure Treg to migrate to the site of contact between paternal Ags and maternal immune cells and to orchestrate immune tolerance toward the fetus.

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“…The hCG-subunits are already transcribed in 8-cell embryos (Bonduelle et al 1988) and the blastocyst has been shown to secrete relatively high concentrations of bioactive hormone (Lopata and Hay 1989). Since hCG is produced by syncytiotrophoblasts after the fusion of cytotrophoblasts as a function of trophoblast differentiation (Hoshina et al 1985), and several endometrial cytokines considered essential for implantation, such as LIF (Sawai et al 1995) andM-CSF (Garcia-Lloret et al 1994) have been shown to modulate hCG-biosynthesisprobably by interfering with trophoblast differentiation -hCG could well be a key regulator, triggering whether or not the embryo will implant.…”

Section: The Role Of Hcgmentioning

confidence: 99%

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

Licht

Fluhr

Neuwinger³

et al. 2007

Molecular and Cellular Endocrinology

160

115

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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.

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Chorionic gonadotrophin-β mRNA, a trophoblast marker, is expressed in human 8-cell embryos derived from tripronucleate zygotes

Cited by 148 publications

References 9 publications

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)

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)

Human Chorionic Gonadotropin Attracts Regulatory T Cells into the Fetal-Maternal Interface during Early Human Pregnancy

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

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