The molecular regulators of human embryo-uterus interactions

Each year, hundreds of thousands of women around the world experience early pregnancy loss. More than 40% of naturally conceived embryos and 55% of embryos conceived by in vitro fertilization (IVF) fail to properly interact with the uterus, thus terminating pregnancy. Overall, of the total number of pregnancies that are lost, 75% represent a failure of implantation. Our lack of understanding of why most embryos fail to interact with the endometrium, the inner epithelial layer of the uterus, is frustrating to women and their partners. Understanding implantation and improving its management is thus a huge opportunity for public health, including family planning and disease prevention. However, the small size and inaccessibility of the embryo in the womb brings difficulties to conducting studies, especially at the time of implantation. To fill this fundamental gap in our knowledge, in this project, we will use a complex implantation model including human blastoids and uterus organoids formed from stem cells. We will use this model to define subpopulations of uterine cells that might play specific roles at the time of implantation and to infer molecular mechanisms driving the uterus for implantation. In the last part of the project, we will look for the malfunctions occurring in patients diagnosed with repeated implantation failure (RIF). RIF is a severe obstacle in human assisted reproduction treatment with a significant impact both on health providers and on infertile couples. When successful, this knowledge could provide a gateway to better understanding of the implantation regulators and to stratifying patient using novel markers of receptivity and ultimately to the development of targeted drugs and treatments.

Each year, hundreds of thousands of women around the world experience early pregnancy loss. More than 40% of naturally conceived embryos and 55% of embryos conceived by in vitro fertilization (IVF) fail to properly interact with the uterus, thus terminating pregnancy. Overall, of the total number of pregnancies that are lost, 75% represent a failure of implantation. Our lack of understanding of why most embryos fail to interact with the endometrium, the inner epithelial layer of the uterus, is frustrating to women and their partners. Understanding implantation and improving its management is thus a huge opportunity for public health, including family planning and disease prevention. However, the small size and inaccessibility of the embryo in the womb brings difficulties to conducting studies, especially at the time of implantation. To fill this fundamental gap in our knowledge, in this project, we developed a complex implantation model including human blastoids and uterus organoids formed from stem cells. We used this model to define subpopulations of cells that might play specific roles at the time of implantation and to infer molecular mechanisms driving the uterus for implantation.