Research Profile - We really need to talk
Some conversations just can't wait – the one with your boss about that raise, the one with your kids about putting down the family pet and the one that happens between an embryo and a uterus.
In fact, there are just three days available for that last conversation – and without it, the embryo isn't going to find its way into the uterus, making pregnancy impossible.
An embryo can implant itself in all sorts of places, says Daniel Dufort. For instance, it can implant in the fallopian tubes, resulting in a potentially life-threatening ectopic pregnancy. The uterus, where it is supposed to insert itself, is actually the hardest environment of all in which to do so.
At a Glance
Who: Dr. Daniel Dufort, Associate Professor, Department of Obstetrics and Gynecology, McGill University
Issue: Despite advances in in vitro fertilization (IVF), success rates remain low, in part because of the failure of embryos to implant.
Approach: Dr. Dufort is trying to determine the role of a specific pathway, the Wnt pathway, in implantation.
Impact: This research could enhance the success of IVF, as well as help couples who experience repeated implantation failures.
That, according to Dr. Dufort, is because the uterus is so close to the outside of the body. Exposed to external environments, it has created what he calls a "dense shield" to protect it from outside invaders. For the embryo to get beyond that shield, there must first be a conversation between the embryo and the uterus.
This "conversation" is like an introduction – uterus, meet embryo, embryo meet uterus. This exchange of information is essential to creating the conditions in each for successful implantation. For example, once the uterus determines that an embryo is present, it can get ready for implantation. Meanwhile, once ready, it needs to "tell" this to the embryo. And, finally, when the embryo "hears" this , it undergoes changes that support implantation, changes that bring adhesion molecules to its surface.
Figuring out just how that conversation happens is the main focus of Dr. Dufort's research. Part of the answer can be found in a kind of protein secreted by embryos called Wnts.
Dr. Dufort believes that this protein pathway is the means by which the conversation takes place. And he is using samples from the IVF clinic at McGill to test his hypothesis.
By analyzing catheters used to transfer embryos into women, he can see which proteins are more common when implantation is successful and which show up more often in unsuccessful implantation efforts.
Deciphering this pathway and its role in the embryo-uterus communication is vitally important to ensuring successful in-vitro fertilization (IVF), Dr. Dufort says.
"We've put lots of effort into creating all these nice healthy embryos, but we're putting them into the mother and we have no idea what will happen," he says.
If a couple is experiencing infertility due to a breakdown in the conversation, all the IVF in the world won't help them, points out Dr. Dufort.
"This is the one area that will be crucial if we want to have successful IVF," he says.
And while his research focuses on humans, it also has applications in the veterinary field, where reproduction among cattle and horses is increasingly carried out by IVF.
No one has done much work on this embryo-uterus communication, says Dr. Dufort. He, himself, came to it essentially by accident. He was studying embryo development, how different parts of an embryo turned into a head, a trunk, legs or arms. And he found proteins present in the embryo that weren't needed for this differentiation, leading him to wonder if they were there to facilitate communication with the uterus.
"It was a lucky guess that turned out to be true," he says.
"If that communication does not occur, then the embryo is lost."
The study
Implantation is a crucial stage in reproduction during which the embryo attaches itself to the wall of the uterus. Without successful implantation, a pregnancy cannot continue. Successful implantation requires interaction between the embryo and the uterus, so that each can prepare itself for this important stage. Dr. Daniel Dufort is examining the role of a signaling pathway called the Wnt pathway in facilitating this interaction and attempting to identify genes whose expression is regulated by the pathway. He is testing the catheters used in embryo transfer in the McGill IVF clinic to see which factors are present during successful implantation and which are more common in unsuccessful implantation.
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