Abstract
The presence of the conceptus in uterine cavity necessitates an elaborate network of interactions between the implanting embryo and a receptive endometrial tissue. We believe that embryo-derived signals play an important role in the remodeling and the extension of endometrial receptivity period. Our previous studies provided original evidence that human Chorionic Gonadotropin (hCG) modulates and potentiates endometrial epithelial as well as stromal cell responsiveness to interleukin 1 (IL1), one of the earliest embryonic signals, which may represent a novel pathway by which the embryo favors its own implantation and growth within the maternal endometrial host. The present study was designed to gain a broader understanding of hCG impact on the modulation of endometrial cell receptivity, and in particular, cell responsiveness to IL1 and the acquisition of growth-promoting phenotype capable of receiving, sustaining, and promoting early and crucial steps of embryonic development. Our results showed significant changes in the expression of genes involved in cell proliferation, immune modulation, tissue remodeling, apoptotic and angiogenic processes. This points to a relevant impact of these embryonic signals on the receptivity of the maternal endometrium, its adaptation to the implanting embryo and the creation of an environment that is favorable for the implantation and the growth of this latter within a new and likely hostile host tissue. Interestingly our data further identified a complex interaction between IL1 and hCG, which, despite a synergistic action on several significant endometrial target genes, may encompass a tight control of endogenous IL1 and extends to other IL1 family members.
Highlights
Embryonic implantation and establishment of successful pregnancy require a dynamic process of interactions between the embryo and a receptive maternal endometrium
Gene expression profile for all experiments Total RNA was isolated from primary human endometrial stromal cell (ESC) treated with human chorionic gonadotropin (hCG) (100 ng/mL) for 24 h before being stimulated or not with IL1B (0.1 ng/mL) for additional 24 h
Because IL18R1 and IL1R-like 1 (IL1RL1) were targeted by hCG/IL1B, we have investigated their ligands (IL18, IL33) by Quantitative real time (qRT)-PCR
Summary
Embryonic implantation and establishment of successful pregnancy require a dynamic process of interactions between the embryo and a receptive maternal endometrium. Numerous studies showed major and specific changes arising within this specific time interval, which encompass adhesion, invasion, survival, growth, differentiation and immune-modulating factors that shape up endometrial receptivity. The dynamics of this transition from a non-receptive to a receptive endometrium are poorly understood, but the correct spatio-temporal synthesis and balance of various factors is thought to play an important role in human uterine preparation for implantation [3,4,5]. Direct interactions at the fetalmaternal interface and appropriate coordination between embryonic and maternal signals at the implantation site are essential for providing the synergistic environment needed for the establishment of pregnancy [6,7]
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