The first embryo-dependent and -independent programming of endometrial function in early pregnancy: a bovine model.

Subfertility represents a major problem in domestic animals and humans. In cattle but also in women, up to 40% of total embryonic losses occur between days 7 and 16 of pregnancy, indicating that early embryonic mortality is a major cause of reproductive failure. A finely tuned synchrony between the competent embryo and a receptive endometrium is the key for optimal embryo development and the establishment of a successful pregnancy. Several studies have indicated the existence of complex paracrine and endocrine in vivo communication between early embryo and the maternal tract in mammals. However, so far there is no evidence that the embryo significantly interacts with the endometrium before elongation in the cow (begins 13 days post-mating) or before real implantation in human (day 10-17), while most of the early embryonic losses happen at that time. To understand the pathways of early pregnancy loss we have to elucidate the physiological molecular and biochemical processes underpinning and regulating the earliest maternal-embryonic cross talk upon the moment of embryo arrival in the uterus. In the present project, using the cow as a proven research model to study the very first developmental stages of the pre-implantation embryo, our central aim is to study the embryo/conceptus and endocrine programming of the endometrium to support pregnancy success. In the first part of the PhD research (Milestones 1 and 2, conducted at the University of São Paulo) we hypothesized that exposure to an embryo changes the abundance of specific transcripts and the biochemical composition of the uterine fluid in the cranial region of the pregnant uterine horn. As such an effect is likely to be very local in nature, we developed an in vivo model that allowed sampling the endometrium closer to the embryo (Sponchiado et al., 2017). To limit the use of experimental animals, in the second part of the PhD research (Milestone 3), we propose to use an innovative in vitro co-culture system to investigate the nature of the specific interaction between bovine embryos and endometrial epithelial cells and how this ultimately may affect early embryo quality. This part of the project will be conducted at the University of Antwerp. The proposed combination of in vivo and in vitro systems with state-of-the art analytical tools of transcriptome and metabolomic research should reveal a plethora of candidate genes and bioactive molecules to understand the pathways of the very first embryo-maternal dialogue. The very first communication between the mother and her embryo is undoubtedly one of the most exciting processes in reproductive biology. The knowledge of these mechanisms should help to understand the problem of early embryo mortality and pregnancy loss leading to disappointing fertility results. Only then it will be possible to build on preventive and even therapeutic measures impacting in pregnancy success both in human and agricultural application.

Keywords:EMBRYO

Disciplines:Animal biology, Genetics, Endocrinology and metabolic diseases, Gynaecology and obstetrics, Nursing, Veterinary medicine

Project type:Collaboration project