Mitigating against life-course complications of heat stress. (360G-Wellcome-227178_Z_23_Z)

Exposure of the mother to extreme heat events while pregnant are reflected in the life course health of the offspring. A critical time of exposure is during the peri-implantation period of pregnancy when: 1) epigenetic determination of cell fate occurs, 2) cues to establish organ systems are established, and 3) molecular and biophysical interactions between the mother and the embryo are also established. There are unknown mechanisms by which acute extreme heat causes peri-implantation pregnancy loss and affects life course health. Mitigation of this is critical if we are to ensure life-course health of babies. We aim to: - Identify how acute extreme heat alters health of the offspring - Determine how heat stress alters life-course development of organ systems - Establish intervention strategies to mitigate against heat-exposed changes to life-course health in offspring Taking an interdisciplinary approach by harnessing our expertise in 1) bioengineered embryo-maternal interaction models, 2) comparative developmental biology of the pig and mammal systems, 3) computational evolutionary biology, we will determine conserved mitigation pathways for intervention in humans to understand the mechanistic biology of heat stress and to identify intervention strategies.