Cambridge Scientists Discover What Actually Happens During Embryo Implantation
A closer look at the structure of an embryo during implantation.
All embryos start off as a bunch of rapidly dividing cells, developing quickly into a compact blastocyst with defined structures. These structures include the inner cell mass (from which every cell in the fetus will be derived) and the trophectoderm, which will later form the placenta.
Post-implantation, embryos are known to transform from a blastocyst to a shape that resembles a cup in a matter of two days; however this mechanism and its intermediates are unknown. While research is routinely conducted on blastocyst growth in-vitro, it is much more complicated to study blastocytsts in utero. As embryos implant into the uterine lining, their new connection with the mother makes it difficult to visualize them.
Researchers at Cambridge University have employed a novel technique to surpass this barrier and investigate what actually occurs in the first two days post-implantation.
This experiment began with the creation of a medium that effectively mimicked the conditions of a uterus. Collagen-coated polyacrylamide matrices were used due to their compatibility with time-lapse imaging. Mice embryos allowed to culture in this medium proliferated along the surface of the gel before successfully developing into the cup structure typical to implanted embryos. During this transformation, the researchers observed a novel intermediate step - the organization of the embryo into the rosette-like structure of polarized cells illustrated above.
Further investigation on the mechanism behind the formation of this rosette intermediate suggested that B1-integrin-mediated signalling at the basal membrane may play a role in cell orientation, with ablation of the B1-integrin subunit gene resulting in a failure to form the structure and embryo death after implantation.
Finally, the researchers investigated lumen formation in the cup-like structure. Anti-adhesive molecules were hypothesized to play a role in this process through the mediation of charge-repulsion between apical membranes, resulting in their separation. This was supported by the observation of Podocalyxin -- an anti-adhesive molecule -- coating the cavity of the epiblast, as well as the surface of the extra-embryonic ectoderm. These two lumens eventually joined to form the lumen of the elongating cup structure.
The discovery of this intermediate is a significant milestone in developmental biology. As emphasized by Dr. Zernicka-Goetz, the author of the study, the findings of this study will likely change the way that embryo development is studied and taught in the future.
"The text books make an educated guess of what happened during this part of development, but we now know that what I learned and what I teach my students about this was totally wrong."