Complement C3 and decay-accelerating factor expression levels are modulated by human chorionic gonadotropin in endometrial compartments during the implantation window.

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Human chorionic gonadotropin (hCG) treatment increased complement C3 mRNA in stromal cells and DAF protein in epithelial cells of the endometrium, suggesting hCG modulates complement protein expression during the implantation window.

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The study examined whether human chorionic gonadotropin (hCG) modulates complement regulation factors in human endometrium during the implantation window, using in vivo treatment of 12 fertile women and in vitro endometrial explant cultures. Endometrial compartment localization and gene expression were assessed by immunohistochemistry and laser capture microdissection followed by RT-PCR, with C3 and DAF protein changes measured by Western blotting in explants. After hCG exposure, C3 mRNA increased in stromal cells and decay-accelerating factor (DAF/CD55) increased in luminal epithelial cells, and progesterone receptor inhibition with RU486 blocked the hCG-induced increases in C3 and DAF. This paper is centrally about endometriosis — it reports an hCG-mediated embryo–endometrium complement signaling mechanism that is relevant to endometriosis-associated alterations in endometrial receptivity and immune regulation.

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Abstract

The control of complement activation in the embryo-maternal environment has been demonstrated to be critical for embryo survival. Complement proteins are expressed in the human endometrium; however, the modulation of this expression by embryo signals has not been explored. To assess the expression of complement proteins in response to human chorionic gonadotropin (hCG), we designed an experimental study using in vivo and in vitro models. Twelve fertile women were treated with hCG or left untreated during the mid-luteal phase, and an endometrial biopsy was performed 24 hours later. The localizations of C3, membrane cofactor protein (MCP; CD46), decay-accelerating factor (DAF; CD55), and protectin (CD59) were assessed by immunohistochemistry, and the messenger RNA (mRNA) levels of these proteins were quantified by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in cells harvested from endometrial compartments using laser capture microdissection. Endometrial explants were cultured with or without hCG for 24 hours, and the C3 and DAF protein levels were measured by Western blotting. Elevated C3 mRNA levels in stromal cells and elevated DAF levels in epithelial luminal cells were detected after hCG treatment. In the endometrial explant model, the progesterone receptor antagonist RU486 inhibited the increases in the levels of C3 and DAF in response to hCG. The findings of this study indicate that hCG plays a role in embryo-endometrium communication and affects the expression of complement proteins in endometrial compartments during the implantation window.
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Abstract

The control of complement activation in the embryo–maternal environment has been demonstrated to be critical for embryo survival. Complement proteins are expressed in the human endometrium; however, the modulation of this expression by embryo signals has not been explored. To assess the expression of complement proteins in response to human chorionic gonadotropin (hCG), we designed an experimental study using in vivo and in vitro models. Twelve fertile women were treated with hCG or left untreated during the mid-luteal phase, and an endometrial biopsy was performed 24 hours later. The localizations of C3, membrane cofactor protein (MCP; CD46), decay-accelerating factor (DAF; CD55), and protectin (CD59) were assessed by immunohistochemistry, and the messenger RNA (mRNA) levels of these proteins were quantified by real-time reverse transcriptase–polymerase chain reaction (RT-PCR) in cells harvested from endometrial compartments using laser capture microdissection. Endometrial explants were cultured with or without hCG for 24 hours, and the C3 and DAF protein levels were measured by Western blotting. Elevated C3 mRNA levels in stromal cells and elevated DAF levels in epithelial luminal cells were detected after hCG treatment. In the endometrial explant model, the progesterone receptor antagonist RU486 inhibited the increases in the levels of C3 and DAF in response to hCG. The findings of this study indicate that hCG plays a role in embryo–endometrium communication and affects the expression of complement proteins in endometrial compartments during the implantation window. Similar content being viewed by others

References

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