The black box of pregnancy first steps

The first steps of human pregnancy remain a black box as they occur hidden in the womb. After fertilization, the egg develops into a blastocyst that attaches to the inner lining of the uterus (endometrium) to implant and develop. An optimal interaction between the embryo and endometrium is critical for a successful pregnancy. However, our understanding is very limited, mainly due to the inaccessibility and the lack of suitable in vitro study models. Recently, we have succeeded in developing a human in vitro implantation model by combining physiological replicas of the endometrium and blastocysts that reliably recapitulate the initial events of attachment and development. Now, we will apply this model to decipher in detail the first steps of human pregnancy at single cell resolution by studying blastocyst adhesion to and interaction with the endometrium. Our detailed investigation will provide deep insights into both normal and eventually dysfunctional processes at the embryo-endometrial interface holding strong potentialto expose targets for treating infertility and improving assisted reproduction (IVF). More generally, our study will provide a roadmap for deciphering the mechanisms of deficient embryo-endometrium interaction in female fertility disorders, offering groundbreaking potential for reproductive biology.