Diálogo entre el embrión y el endometrio durante la implantación humana: un enfoque en los determinantes moleculares y el entorno macrobiano.

Abstract

Implantation failure is a major cause of human infertility and currently the most limiting step in Assisted Reproductive Technologies (ART). It can be caused by both maternal and embryonic factors, as well as by defective crosstalk between them. Due to technical and ethical limitations, it is not possible to study human implantation in vivo. The knowledge about implantation has been mainly obtained from animal models which fail to represent the physiology of the human process. Additionally, a number of in vitro studies have investigated the molecular mechanisms underlying implantation, mostly focussing on either the embryo or the endometrium in a unilateral manner. Many authors have also tried to use indirect, non-invasive approaches to predict implantation success. Despite these efforts, the molecular and environmental determinants precluding pregnancy success remain largely unknown. In this thesis, we used an in vitro model to study the embryo-endometrium interactions during the early stages of implantation. In a first approach, we focused on the different transcriptional responses of the system upon attachment according to the epithelial receptivity (co-culture of trophoblast spheroids with receptive vs. non-receptive endometrial epithelium). The results showed that the receptive epithelium is able to trigger a transcriptional response to the trophoblast challenge otherwise muted when it is non-receptive. We further characterized the transcriptional dynamics at earlier time points during the attachment of the trophoblast to the receptive epithelium, aiming to mimic the successful establishment of pregnancy. It resulted in a series of dynamic changes in gene expression, characterized by an early and transient transcriptional up-regulation in the receptive epithelium, while the trophoblast response was more dynamic. Using an in silico integrative strategy, we predicted the trophoblast and endometrial protein pairs that interact during these different time points and could mediate attachment and early invasion during implantation. Finally, we used an indirect approach to investigate the environmental determinants influencing implantation by evaluating the vaginal microbiota composition at the day of embryo transfer and its relationship with the reproductive outcomes. Our data suggested that vaginal microbiota profile at the embryo transfer does not directly affect implantation in women undergoing IVF with donated oocytes.

Date of Award	19 Jul 2019
Original language	Spanish
Supervisor	Rita Vassena (Director), Josep Santalo Pedro (Director) & Josep Santalo Pedro (Tutor)