Complement C3 and Decay-Accelerating Factor Expression Levels Are Modulated by Human Chorionic Gonadotropin in Endometrial Compartments During the Implantation Window

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.

Human Chorionic Gonadotrophin: New Pleiotropic Functions for an “Old” Hormone During Pregnancy

“…One study has shown that hCG plays a role in this complement control, particularly on decay accelerating factor (DAF) and C3 protein, in in vitro and in vivo models (112).…”

Intrauterine infusion of human chorionic gonadotropin before embryo transfer in IVF/ET cycle: The critical review

“…57 C3 is localized in stromal and glandular compartments during secretory phase. 60 Consequently, hCG might function as an immune modulator responsible of the control of the complement system in the human endometrium. Overactivated complement C3 compromised fetal survival and led to fetal loss.…”

“…Moreover, decay-accelerating factor (DAF), one of complement regulatory proteins to protect host cells from the attack by the activated complement system, was increased in the luminal compartment, potentially to maintain a safe environment for embryonic implantation. 60 Consequently, hCG might function as an immune modulator responsible of the control of the complement system in the human endometrium. Recently, high dose (10 000 IU) of urine-purified hCG was shown to modulate uterine natural killer (uNK) cell proliferation via mannose receptors (CD206), rather than by the classical LH/hCG receptors which are not expressed on uNK cells.…”

Outcome of Intrauterine Injection of Human Chorionic Gonadotropin before Embryo Transfer in Patients with Previous Ivf/Icsi Failure: A Randomized Study

“…Our study clearly correlated with other various studies done all over the world. [4][5][6][7][8][9][10][11] The intrauterine injection of hCG before the No. of embryo per transfer 2.9 ± 0.4 2.9 ± 0.5 embryo transfer is a simple procedure.…”

“…9 It was reported that in several studies about the increase in C3 protein mRNA levels stromal cells in the endometrial biopsy culture of an infertile women during implantation window. 10 There is a definite positive correlation between beta-hCG concentration and implantation rates. 11 Studies are still being conducted in this field of interest.…”