Bilateral BBSRC-FAPESP: Understanding novel conceptus-maternal communication is the key to improving pregnancy outcome in cattle.

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We know that Agriculture and Food security are of critical importance if we are to feed an increasing population with reduced resources. One factor that greatly affects the economic sustainability of both beef and dairy farming is the length of time it takes for either heifers or cows to establish and maintain successful early pregnancy. Increasing fertility in dairy and beef cattle can improve agriculture efficiency with a long term decrease in agriculture impacts worldwide. A major source of pregnancy loss in cattle occurs in the first 3 weeks of pregnancy and the question of when exactly this embryo loss occurs is unknown. What we do know is that successful communication between the embryo and the maternal uterine environment is crucial for successful early pregnancy. There are three key interactions that need to occur 1) the hormone progesterone needs to act on the endometrium (the tissue that lines the inner part of the uterus) to provide a suitable environment to host the embryo, 2) the embryo must undergo a rapid period of growth which is only possible in the uterus i.e. we cannot recapitulate this in the lab and 3) the conceptus must successfully signal its presence to the mother to sustain early pregnancy.Over the last number of years my work has focused on using a specific type of technology to help address the question of how the uterine environment and the conceptus (which is the embryo proper that forms the calf and the extra-embryonic membrane which forms the placenta) interact with one another. The technologies I have use have focused on transcriptomics and proteomics. Instead of investigating how one gene or protein changes in a given condition e.g. in early pregnancy these technologies allow us to investigate how the expression of lots of genes and/or proteins change in early pregnancy. This gives us a much broader picture of what is occurring both during successful early pregnancy, but also when early pregnancy loss occurs. The main focus of my research has been on 1) the role that a specific hormone progesterone plays in providing a good or insufficient uterine environment to promote successful early pregnancy 2) how the maternal environment responds to the conceptus and 3) if we can use these gene or proteins we have identified as interacting between the conceptus and the endometrium to detect successful early pregnancy in a non-invasive sample matrix.More recently my work has identified that key proteins and molecules, packaged in vesicles that can be released from one cell type e.g. the conceptus and alter a different cell type e.g. the endometrium. I have also shown that the way in which these interactions occur may be different when a male conceptus is present compared to a female conceptus.The objectives of the research program are to determine what components of these vesicles are taken up by the endometrium and alter its function. We will also determine how the communication by these vesicles differs between embryos that have different likely hood of pregnancy success (those generated in an animal which are of high quality compared with those generated using assisted reproductive technologies which have less chance of success). We will also examine how male and female conceptuses signal in a different manner to one another. Collectively the results from this work will lead to 1) enhanced understanding of what drives pregnancy success/ embryo loss, 2) novel targets to intervene to prevent embryo loss and 3) markers of successful early pregnancy.