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The human placenta is a multifunctional, disc-shaped temporary fetal organ that develops in the uterus during pregnancy, connecting the mother and the fetus. The availability of large-scale datasets on the gene expression of placental cell types and scholarly articles documenting adverse pregnancy outcomes from maternal infection warrants the use of computational resources to aid in knowledge generation from disparate data sources. Using maternal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection as a case study in microbial infection, we constructed integrated datasets and implemented visual analytics resources to facilitate robust investigations of placental gene expression data in the dimensions of flow, curation, and analytics. The visual analytics resources and associated datasets can support a greater understanding of SARS-CoV-2-induced changes to the human placental expression levels of 18,882 protein-coding genes and at least 1233 human gene groups/families. We focus this report on the human aquaporin gene family that encodes small integral membrane proteins initially studied for their roles in water transport across cell membranes. Aquaporin-9 (AQP9) was the only aquaporin downregulated in term placental villi from SARS-CoV-2-positive mothers. Previous studies have found that (1) oxygen signaling modulates placental development; (2) oxygen tension could modulate AQP9 expression in the human placenta; and (3) SARS-CoV-2 can disrupt the formation of oxygen-carrying red blood cells in the placenta. Thus, future research could be performed on microbial infection-induced changes to (1) the placental hematopoietic stem and progenitor cells; and (2) placental expression of human aquaporin genes, especially AQP9.
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Molecular signatures of placentation and secretion uncovered in Poeciliopsis maternal follicles
Abstract Placentation evolved many times independently in vertebrates. While the core functions of all placentas are similar, we know less about how this similarity extends to the molecular level. Here we study Poeciliopsis, a unique genus of live-bearing fish that have independently evolved complex placental structures at least three times. The maternal follicle is a key component of these structures. It envelops yolk rich eggs and is morphologically simple in lecithotrophic species, but has elaborate villous structures in matrotrophic species. Through sequencing the follicle transcriptome of a matrotrophic, P. retropinna, and lecithotrophic, P. turrubarensis, species we found genes known to be critical for placenta function expressed in both species despite their difference in complexity. Additionally, when we compare the transcriptome of different river populations of P. retropinna, known to vary in maternal provisioning, we find differential expression of secretory genes expressed specifically in the top layer of villi cells in the maternal follicle. This provides some of the first evidence that the placental structures of Poeciliopsis function using a secretory mechanism rather than direct contact with maternal circulation. Finally, when we look at the expression of placenta proteins at the maternal-fetal interface of a larger sampling of Poeciliopsis species, we find expression of key maternal and fetal placenta proteins in their cognate tissue types of all species, but follicle expression of Prolactin is restricted to only matrotrophic species. Taken together, we suggest that all Poeciliopsis follicles are poised for placenta function, but require expression of key genes to form secretory villi.
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- Award ID(s):
- 1754669
- PAR ID:
- 10160454
- Date Published:
- Journal Name:
- Molecular Biology and Evolution
- ISSN:
- 0737-4038
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Wheat, Christopher (Ed.)Abstract The blackstripe livebearer Poeciliopsis prolifica is a live-bearing fish belonging to the family Poeciliidae with high level of postfertilization maternal investment (matrotrophy). This viviparous matrotrophic species has evolved a structure similarly to the mammalian placenta. Placentas have independently evolved multiple times in Poeciliidae from nonplacental ancestors, which provide an opportunity to study the placental evolution. However, there is a lack of high-quality reference genomes for the placental species in Poeciliidae. In this study, we present a 674 Mb assembly of P. prolifica in 504 contigs with excellent continuity (contig N50 7.7 Mb) and completeness (97.2% Benchmarking Universal Single-Copy Orthologs [BUSCO] completeness score, including 92.6% single-copy and 4.6% duplicated BUSCO score). A total of 27,227 protein-coding genes were annotated from the merged datasets based on bioinformatic prediction, RNA sequencing and homology evidence. Phylogenomic analyses revealed that P. prolifica diverged from the guppy (Poecilia reticulata) ∼19 Ma. Our research provides the necessary resources and the genomic toolkit for investigating the genetic underpinning of placentation.more » « less
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Environmental hypoxia challenges female reproductive physiology in placental mammals, increasing rates of gestational complications. Adaptation to high elevation has limited many of these effects in humans and other mammals, offering potential insight into the developmental processes that lead to and protect against hypoxia-related gestational complications. However, our understanding of these adaptations has been hampered by a lack of experimental work linking the functional, regulatory, and genetic underpinnings of gestational development in locally adapted populations. Here, we dissect high-elevation adaptation in the reproductive physiology of deer mice (Peromyscus maniculatus), a rodent species with an exceptionally broad elevational distribution that has emerged as a model for hypoxia adaptation. Using experimental acclimations, we show that lowland mice experience pronounced fetal growth restriction when challenged with gestational hypoxia, while highland mice maintain normal growth by expanding the compartment of the placenta that facilitates nutrient and gas exchange between gestational parent and fetus. We then use compartment-specific transcriptome analyses to show that adaptive structural remodeling of the placenta is coincident with widespread changes in gene expression within this same compartment. Genes associated with fetal growth in deer mice significantly overlap with genes involved in human placental development, pointing to conserved or convergent pathways underlying these processes. Finally, we overlay our results with genetic data from natural populations to identify candidate genes and genomic features that contribute to these placental adaptations. Collectively, these experiments advance our understanding of adaptation to hypoxic environments by revealing physiological and genetic mechanisms that shape fetal growth trajectories under maternal hypoxia.more » « less
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Background: The placenta is a temporary organ that develops throughout pregnancy, connecting a developing fetus to the maternal uterine wall. The placenta’s structure is species specific and complex, resulting in recent advancements with in vitro models to help study this dynamic organ. The main cell type composing the placenta, trophoblast cells, serve several roles and have been incorporated within biomaterials and devices to recapitulate the placental microenvironment. Summary: This review highlights in vitro 2D, 3D, and on-a-chip models of two placental interfaces: the interface between the endometrium and extravillous trophoblast cells and the interface between the chorionic villi and intervillous space. First, an overview of placental cell types and in vitro model types used in the discussed studies is provided. Next, models of invasive trophoblasts cells at the endometrium where the placenta is anchored and the spiral arteries are remodeled are discussed. Next, the review highlights models of the chorionic villi and intervillous space, an interface where cytotrophoblast cells fuse into syncytiotrophoblasts. Finally, we discuss key takeaways and future directions in creating representative placental models.Key Messages: The combination of biomaterial and engineering approaches has led to the development of physiologically relevant models, allowing placental trophoblast functions to be investigated with more clarity. Each cell type (e.g. trophoblast cell line vs. stem cells vs. primary placental cells) and biomaterial system (e.g. organoid vs. on-a-chip) that is selected for a given model has a unique combination of advantages and limitations, which are detailed within this review. Overall, the placental models discussed enable trophoblast cell behavior to be studied in vitro with the inclusion of extracellular matrix materials, growth factors, and other environmental cues. While one model alone does not fully recapitulate every function of the placenta, individual models are tailored to inform on specific placental trophoblast behaviors.more » « less
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Abstract The human placenta is a critical organ, mediating the exchange of nutrients, oxygen, and waste products between fetus and mother. Placental malaria (PM) resulted from Plasmodium falciparum infections causes up to 200 thousand newborn deaths annually, mainly due to low birth weight, as well as 10 thousand mother deaths. In this work, a placenta-on-a-chip model is developed to mimic the nutrient exchange between the fetus and mother under the influence of PM. In this model, trophoblasts cells (facing infected or uninfected blood simulating maternal blood and termed “trophoblast side”) and human umbilical vein endothelial cells (facing uninfected blood simulating fetal blood and termed “endothelial” side) are cultured on the opposite sides of an extracellular matrix gel in a compartmental microfluidic system, forming a physiological barrier between the co-flow tubular structure to mimic a simplified maternal–fetal interface in placental villi. The influences of infected erythrocytes (IEs) sequestration through cytoadhesion to chondroitin sulfate A (CSA) expressed on the surface of trophoblast cells, a critical feature of PM, on glucose transfer efficiency across the placental barrier was studied. To create glucose gradients across the barrier, uninfected erythrocyte or IE suspension with a higher glucose concentration was introduced into the “trophoblast side” and a culture medium with lower glucose concentration was introduced into the “endothelial side”. The glucose levels in the endothelial channel in response to CSA-adherent erythrocytes infected with CS2 line of parasites in trophoblast channel under flow conditions was monitored. Uninfected erythrocytes served as a negative control. The results demonstrated that CSA-binding IEs added resistance to the simulated placental barrier for glucose perfusion and decreased the glucose transfer across this barrier. The results of this study can be used for better understanding of PM pathology and development of models useful in studying potential treatment of PM.more » « less
- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1093/molbev/msaa121
