HEALTHYFOETUS · Unravelling the effect of divergent concentrations of progesterone in early pregnancy on foetal development in the cow

Uterine receptivity and the dialogue between the embryo and the mother in early pregnancy is mainly driven by the concentrations of the steroid hormone progesterone (P4). Work from the host laboratory has shown that divergent P4 concentrations early in pregnancy strongly influence embryo growth and survival in cattle but are not always associated with improved pregnancy rates. Importantly, the consequences of suboptimal P4 for later foetal development are largely unknown. This project proposes four Research work packages (WP) to interrogate the effect of P4 concentration early in pregnancy on the development of the maternal-placental-foetal unit in the cow. The first three WP are built around two groups of cows, manipulated to have high or low P4 during the first days of pregnancy, and a third untreated group, as control. In WP1, foetal growth will be followed through ultrasound scanning until four months of pregnancy (~40% of gestation), when the foetus and associated membranes will be recovered for WP2 and 3. Development of the placenta and amniotic fluid composition will be assessed through transcriptomics and metabolomics, respectively, in WP2. Foetal maturity will be determined in WP3, through organ measurements and histology, and transcriptomic analysis of the hypothalamus (a pivotal organ for development). In WP4, endogenous P4 in dairy cattle across pregnancy will be correlated with calf birth weight. In addition, WP5, 6 and 7 will deal with Management, Training, and Dissemination, respectively. Modelling of metabolomic and transcriptomic data will increase knowledge of the functional and molecular regulation of bovine pregnancy and foetal physiology. Furthermore, this novel information could lead to new therapeutics to optimise the development of a healthy offspring. This truly multidisciplinary project will be accomplished thanks to the facilities in the host institution, the vast experience of the supervisor, and the complementary expertise of the Fellow.