Pregnant Female Reproductive Tissue Mapping Center Organ Specific Project

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SUMMARY The goal of the OSP is to generate the data needed to build three-dimensional multiscale maps of the human placenta from healthy uncomplicated pregnancies. OSP1 will interact with the OAC and DAC, as well as other HuBMAP Centers, to facilitate data and resource sharing across the Consortium and with the broader scientific community. The placenta is the interface between mother and fetus, mediating exchange of nutrients and metabolic wastes and producing endocrine signals that promote maintenance of the pregnancy and proper fetal growth. The placenta is comprised largely of cells of fetal origin, including stromal cells, capillary endothelial cells, and three types of trophoblast: proliferative cytotrophoblast; hormone-producing and transport-mediating syncytiotrophoblast; and invasive extravillous trophoblast. The placenta also contains fetal and maternal immune cells, which mediate immunologic responses to infection and may play roles in placental development. Abnormalities in placental development and function have been linked to the most common and serious complications of pregnancy, but details of the mechanisms leading to adverse pregnancy outcomes remain to be elucidated. The complementary strengths of our investigative team enable us to obtain prenatal in vivo MRI and ultrasound imaging data and post-delivery molecular profiling data from the same organs. Rigorous pre-analytical and characterization pipelines will ensure collection of high-quality biospecimens and generation of reproducible data. A range of advanced molecular profiling techniques will be used, including bulk and single-nucleus transcriptomic, chromatin accessibility, and extracellular matrix proteomic profiling, and high-resolution multiplexed spatial transcriptomic and imaging mass cytometry technologies. We will combine a survey approach (in which we will collect data from a small number of samples/sections from many subjects, which will allow us to detect potential differences associated with variables such as fetal sex, mode of delivery, or maternal factors) with a deep dive approach (in which we will collect data from many serial sections from a small number tissue blocks, to build a detailed model of tissue architecture). To generate foundational knowledge to serve as the basis of future studies aimed at identifying the structural and functional perturbations that underlie placental dysfunction-mediated pregnancy complications, we propose two Sub- Aims: C.1. To generate a reference dataset from normal term placentas, uterine endomyometrium, fallopian tubes, and maternal serum, to enable construction of 3D multiscale maps of these normal pregnant reproductive tissues at term, and to map extracellular RNA-mediated signaling between the placenta and maternal tissues; and C.2. To generate a reference dataset from placentas across gestation, to enable construction of 3D multiscale maps of the developing human placenta, and tracking of the differentiation and migration of the cells within it.