From mice to rhinos: Whole-organ quantification of 3D mammalian placental structure using correlative multiscale...

The mammalian placenta displays extraordinary structural diversity across scales of measurement, yet the quantitative basis and functional consequences of this variation remain poorly understood. Traditional approaches rely on qualitative categories or simple metrics such as length or depth which obscure the complexity of three-dimensional (3D) tissue architecture. Here, we review methods for quantifying whole-organ placental volume, surface area, and vascular organisation, highlighting trade-offs between speed, expense, labour, precision, scalability, destructivity, and specificity. We then demonstrate how correlative multiscale 3D imaging techniques can overcome these limitations, enabling whole-organ quantification across species spanning several orders of magnitude in placental volume-from mouse to rhinoceros. Using integrated workflows that combine X-ray microfocus tomography (microCT), light (H&E histology), and electron (SBF-SEM) microscopy, we generate quantitative structural datasets across spatial scales. In a mouse placenta, correlative 3D X-ray histology (3D-XRH) links histological features directly to their 3D tissue context. In a human placenta, multimodal imaging integrates whole-organ microCT with correlative X-ray and electron microscopy (CXEM) to quantify the total exchange surface area, bridging organ-scale structure and ultrastructural detail. Finally, using placentas from giraffes and rhinos, we show how microCT can be used to quantify the whole organ structure of placentas from even very large mammals, quantifying metrics such as cotyledon volume distribution and blood vessel architecture. Together, these examples illustrate the power of correlative multiscale 3D imaging to resolve mammalian placental structure, bridging cellular and organ-level organisation. This integrative approach provides a unified framework for quantitative comparative placentation, linking structural diversity to physiological function.