Embryo signals for successful implantation
mesheuropmc: embryonic structures | animal structures
Human pre-implantation embryos display a high prevalence of aneuploidy and chromosomal mosaicism, unique from any other species. The decreasing incidence of aneuploidy observed between the cleavage and blastocyst stages of preimplantation embryo development infers a degree of 'self-correction' following activation of the embryonic genome. However, contrary to the previous assumption that only euploid embryos should be considered 'normal', new evidence has confirmed that mosaic embryos can result in the birth of healthy babies. Thus, aneuploidy should be viewed as an intrinsic feature of human pre-implantation embryo development, which presents a novel challenge at implantation. The endometrium must implement both positive and negative selection, in order to limit maternal investment to only viable embryos. The ability of the endometrium to act as a 'biosensor' of embryo quality has been well documented yet there is little direct evidence for the key regulators of this process.\ud \ud For the first time, we demonstrate a biological context for embryo biosensoring. Firstly, we discover novel embryo-secreted proteases that are enhanced at the blastocyst stage and relate to implantation outcome upon embryo transfer. Secondly, we identify corresponding protease-sensitive receptors in the endometrium, heightened during the window of implantation. By demonstrating the cleavage and de-activation of endometrial toll-like receptor 4 (TLR4) by embryo conditioned medium, we link successful implantation to a diminished inflammatory response. Furthermore, we demonstrate that TLR4 levels in the endometrium constitute a selectivity checkpoint, which is supressed in women suffering from recurrent miscarriage (RM).