Abstract
Successful implantation requires the coordinated migration and invasion of trophoblast cells from out of the blastocyst and into the endometrium. This process relies on signals produced by cells in the maternal endometrium. However, the relative contribution of stroma cells remains unclear. The study of human implantation has major technical limitations, therefore the need of in vitro models to elucidate the molecular mechanisms. Using a recently described 3D in vitro models we evaluated the interaction between trophoblasts and human endometrial stroma cells (hESC), we assessed the process of trophoblast migration and invasion in the presence of stroma derived factors. We demonstrate that hESC promotes trophoblast invasion through the generation of an inflammatory environment modulated by TNF-α. We also show the role of stromal derived IL-17 as a promoter of trophoblast migration through the induction of essential genes that confer invasive capacity to cells of the trophectoderm. In conclusion, we describe the characterization of a cellular inflammatory network that may be important for blastocyst implantation. Our findings provide a new insight into the complexity of the implantation process and reveal the importance of inflammation for embryo implantation.
Highlights
Despite advances in fertility treatments and assisted reproductive technologies (ART), infertility is still a major global health concern that affects nearly 15% of all couples [1,2,3,4]
blastocyst-like spheroids (BLS) were transferred into individual wells of a 96-well plate containing conditioned media (CM) from HEC-1A, human endometrial stroma cells (hESC), or Dulbecco’s Modified Eagle’s medium (DMEM)/F-12 growth medium supplemented with low serum (1% fetal bovine serum (FBS)) as a control (Conditioned Media for all the cells was prepared using 1% FBS)
We report the characterization of an inflammatory network that is modulated by endometrial stroma cells, which is responsible for the regulation of trophoblast migration and invasion
Summary
Despite advances in fertility treatments and assisted reproductive technologies (ART), infertility is still a major global health concern that affects nearly 15% of all couples [1,2,3,4]. Embryo implantation is an essential prelude for successful pregnancy. Implantation will only take place in a receptive uterus endometrial uterine receptivity is still the major rate limiting factor for successful pregnancies [2, 8, 9]. The endometrium becomes receptive between days 19 – 23, of a normal human menstrual cycle, which is referred to as the window of implantation (WOI). This window is induced through increased levels of 17-b-estradiol and progesterone and results in several endometrial changes [10,11,12]. Several different cellular components, including cytokines, chemokines, growth factors, and adhesion molecules, are required for implantation [8, 13, 14]
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