Feto-placental vascular structure and in silico haemodynamics: of mice, rats, and human

The complex arborization of the feto-placental vasculature is crucial for optimal fetal nutrition, waste exchange and ultimately, development. Ethical and experimental limitations constrain research into the human placenta, hence experimental animal models such as mice and rats, are crucial to understand placental function. However, it is unclear how well the mouse and rat feto-placental vascular structure emulates human. Moreover, the implications of differences in vascular structure, especially in arborization, for placental function remain unclear. We use micro-computed tomography imaging, high frequency Doppler ultrasound and computational fluid dynamics to characterize feto-placental vasculature in mice, rats, and humans. Our data suggest that despite structural differences between rat and mouse placenta, haemodynamics are similar and that both hold applicability to investigating feto-placental structure and function. We show that human cotyledons demonstrate vascularity-dependent haemodynamic behaviour (including flow deceleration and oxygen exchange) similar to rodents and can be analysed in the same spectrum as rodents. Finally, we show strong structure-function relationships when interspecies datasets are combined; notably, we demonstrate that surrogate measures such as vascularity, can be used to estimate placental oxygen exchange function. Thus pre-clinical placental research utilising rat and mouse placentae to understand the impact of feto-placental arborization on placental function and fetal development, can inform the human context.