Placenta最新文献

The placenta and uterus are essential to healthy human pregnancy, yet their complex adaptation and function remain difficult to study, particularly during the second trimester. Historical collections of placenta in situ specimens, including the Boyd, Dixon, and Carnegie Collections, provide rare access to placental and uterine anatomy across developmental stages and pathological conditions. Due to advancements in obstetric care, the preparation and extent of specimens in these collections is uncommon nowadays. They therefore offer a unique window into pregnancy that contemporary imaging cannot fully reproduce. This review article briefly summarizes these historical collections and examines how they can be integrated with modern imaging, machine learning, and multiscale modeling to extend their research utility. Advances in computational methods support the digitization and 3D reconstruction of 2D histological sections, helping to mitigate issues such as tissue deformation, staining variability, and missing sections. In addition, machine learning approaches enable automated segmentation, facilitating more detailed characterization of utero-placental structures and associated physiological functions. Image-based multiscale modeling can link microscale features, such as villous capillary architecture, to organ-scale responses including global perfusion and oxygen transport, while enabling efficient computation when enhanced with physics-informed neural networks or neural operators. These methods preserve the scientific value of legacy specimens while enabling new avenues for studying pregnancy complications such as preeclampsia and fetal growth restriction. By combining legacy resources with contemporary analytical techniques in an interdisciplinary framework, a more thorough understanding of placental biology and maternal-fetal health can be achieved that may inform future research and clinical applications.

The differentiation of cytotrophoblast (CTB) into extravillous trophoblast (EVT) is central to development of the human placenta. This review explores the process by which CTB differentiate into invasive EVT. At its core is a mechanism known as the epithelial-mesenchymal transition (EMT), whereby immobile epithelial cells are transformed into an invasive, mesenchymal phenotype. Analysis of EMT-associated genes in first trimester CTB and EVT shows clear evidence of an EMT, promoting transition from CTB to EVT. The same analysis of third trimester cells shows evidence of an MET (mesenchymal-epithelial transition); EVT regress from the invasive first trimester mesenchymal phenotype to one characterized as mesenchymal but non-motile and non-proliferative. Of the EMT-master regulators, only the expression of the ZEB2 transcription factor showed a major increase in expression in first trimester EVT, which then reversed in third trimester cells. Overexpression of ZEB2 in trophoblast cell lines led to a pro-EMT shift in molecular markers, a more mesenchymal morphology and increased invasiveness, confirming its probable role in stimulating first trimester EMT. To confirm and compare the EMT observed in EVT with the several known types of EMT, we conducted a deeper gene expression analysis, enabling development of a trophoblast-specific EMT signature. Analysis of DNA methylation revealed genome-wide hypomethylation of third trimester EVT but also a small geneset with gains of methylation. EMT-associated genes showing a gain of methylation and differential expression comprised both pro-EMT and pro-MET genes, suggesting a regulated balance, maintaining the third trimester phenotype. The existence of multiple phenotypes on the EMT spectrum supports the concept of trophoblast epithelial-mesenchymal plasticity (EMP), with EMT-mediated generation of invasive first trimester cells followed by MET-assisted regression to the third trimester phenotype.

The placenta establishes a continuous epithelial barrier that separates maternal and fetal blood. The cell type lining this barrier is the syncytiotrophoblast (STB), an exceptional lineage comprising innumerable nuclei enclosed within a single uninterrupted cytoplasm. The STB mediates nutrient and gas exchange between maternal and fetal circulations and performs vital endocrine functions that modify maternal physiology to sustain pregnancy and support fetal growth. Maintenance of STB integrity is therefore critical for pregnancy success, and dysregulation of its formation and function is implicated in several severe pregnancy complications. As a postmitotic cell layer, STB expansion and renewal depend on underlying cytotrophoblasts exiting their progenitor state and fusing into the syncytium. Consequently, the STB contains nuclei and organelles of diverse ages, maturation states, and potentially distinct functions. Recent findings reveal substantial heterogeneity within STB nuclei, encompassing differences in transcriptional activity and chromatin organization. These variations may reflect nuclear age but could also represent an additional layer of transcriptional and epigenetic regulation required for syncytial function and stability. This review provides an overview of STB development and function, emphasizing epigenetic mechanisms that contribute to the structural and functional diversity of STB nuclei. Key gaps in knowledge are highlighted, including how nuclei interact and whether they can dynamically respond to changes in their local environment. Resolving these and other outstanding questions will advance our understanding of STB development, placental biology, and the pathophysiology of pregnancy complications.

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.