Evolutionary medicine of the mammalian placenta: The interaction between structural variation and physiological function

The placenta is arguably the most structurally diverse organ in mammals, despite sharing a single evolutionary origin and conserved functions. The reasons for this radical structural diversity, and how structure interacts with physiological function, are poorly understood. By understanding how structural divergence affects gestational function in different species, we can apply an ‘evolutionary medicine’ approach to understand human-specific placental disorders, such as pre-eclampsia. We use correlative multiscale imaging techniques (e.g. microCT, volume Election Microscopy) to generate integrated 3D reconstructions of placentas from diverse mammalian species, so that we can computationally model physiological processes (e.g. oxygen diffusion, amino acid transport) within actual tissue architecture. These approaches have revealed multiscale structural adaptations in convergently evolved placental villi (human and horse), how the structure of syncytiotrophoblast microvilli influences amino acid uptake, and how structural variation in the mammalian umbilical cord influences heat flux. Our findings shed important light on reproductive function in humans and animals with biomedical and veterinary ramifications, and contribute towards novel evolutionary hypotheses underpinning placental diversification and human gestational dysfunction.