Placenta accreta spectrum disorder at single-cell resolution: a loss of boundary limits in the decidua and endothelium.

BACKGROUND: Placenta accreta spectrum disorders are associated with severe maternal morbidity and mortality. Placenta accreta spectrum disorders involve excessive adherence of the placenta preventing separation at birth. Traditionally, this condition has been attributed to excessive trophoblast invasion; however, an alternative view is a fundamental defect in decidual biology. OBJECTIVE: This study aimed to gain insights into the understanding of placenta accreta spectrum disorder by using single-cell and spatially resolved transcriptomics to characterize cellular heterogeneity at the maternal-fetal interface in placenta accreta spectrum disorders. STUDY DESIGN: To assess cellular heterogeneity and the function of cell types, single-cell RNA sequencing and spatially resolved transcriptomics were used. A total of 12 placentas were included, 6 placentas with placenta accreta spectrum disorder and 6 controls. For each placenta with placenta accreta spectrum disorder, multiple biopsies were taken at the following sites: placenta accreta spectrum adherent and nonadherent sites in the same placenta. Of note, 2 platforms were used to generate libraries: the 10× Chromium and NanoString GeoMX Digital Spatial Profiler for single-cell and spatially resolved transcriptomes, respectively. Differential gene expression analysis was performed using a suite of bioinformatic tools (Seurat and GeoMxTools R packages). Correction for multiple testing was performed using Clipper. In situ hybridization was performed with RNAscope, and immunohistochemistry was used to assess protein expression. RESULTS: In creating a placenta accreta cell atlas, there were dramatic difference in the transcriptional profile by site of biopsy between placenta accreta spectrum and controls. Most of the differences were noted at the site of adherence; however, differences existed within the placenta between the adherent and nonadherent site of the same placenta in placenta accreta. Among all cell types, the endothelial-stromal populations exhibited the greatest difference in gene expression, driven by changes in collagen genes, namely collagen type III alpha 1 chain (COL3A1), growth factors, epidermal growth factor-like protein 6 (EGFL6), and hepatocyte growth factor (HGF), and angiogenesis-related genes, namely delta-like noncanonical Notch ligand 1 (DLK1) and platelet endothelial cell adhesion molecule-1 (PECAM1). Intraplacental tropism (adherent versus non-adherent sites in the same placenta) was driven by differences in endothelial-stromal cells with notable differences in bone morphogenic protein 5 (BMP5) and osteopontin (SPP1) in the adherent vs nonadherent site of placenta accreta spectrum. CONCLUSION: Placenta accreta spectrum disorders were characterized at single-cell resolution to gain insight into the pathophysiology of the disease. An atlas of the placenta at single cell resolution in accreta allows for understanding in the biology of the intimate maternal and fetal interaction. The contributions of stromal and endothelial cells were demonstrated through alterations in the extracellular matrix, growth factors, and angiogenesis. Transcriptional and protein changes in the stroma of placenta accreta spectrum shift the etiologic explanation away from "invasive trophoblast" to "loss of boundary limits" in the decidua. Gene targets identified in this study may be used to refine diagnostic assays in early pregnancy, track disease progression over time, and inform therapeutic discoveries.

Severe COVID-19 in pregnancy has a distinct serum profile, including greater complement activation and dysregulation of serum lipids.

BACKGROUND: Pregnancies complicated by Coronavirus Disease 2019 (COVID-19) are at an increased risk of severe morbidity due to physiologic changes in immunologic, cardiovascular, and respiratory function. There is little is known about how severity of COVID-19 changes protein and metabolite expression in pregnancy. OBJECTIVE: This study aims to investigate the pathophysiology behind various clinical trajectories in pregnant patients diagnosed with COVID-19 using multi-omics profiling. STUDY DESIGN: This is a prospective cohort study of 30 pregnant patients at a single tertiary care center. Participants were categorized by severity of COVID-19 disease (control, asymptomatic, mild/moderate, or severe). Maternal serum samples underwent LC-MS-based multiomics analysis for profiling of proteins, lipids, electrolytes, and metabolites. Linear regression models were used to assess how disease severity related to analyte levels. Reactome pathway enrichment analysis was conducted on differential analytes. RESULTS: Of 30 participants, 25 had confirmed diagnosis of COVID-19 (6 asymptomatic (one post-infection), 13 mild/moderate (all post-infection), 6 severe), and 5 participants were controls. Severe COVID-19 was associated with distinct profiles demonstrating significant proteomic and lipidomic signatures which were enriched for annotations related to complement and antibody activity. (FDR < 0.05). Downregulated analytes were not significantly enriched but consisted of annotation terms related to lipoprotein activity (FDR > 0.2). Post-infection mild/moderate COVID-19 did not have significantly altered serum protein, metabolite, or lipid metabolite levels compared to controls. CONCLUSIONS: Pregnancies with severe COVID-19 demonstrate greater inflammation and complement activation and dysregulation of serum lipids. This altered multiomic expression provides insight into the pathophysiology of severe COVID-19 in pregnancy and may serve as potential indicators for adverse pregnancy outcomes.

Pregnancy care in solid organ transplant recipients.

Recipients of solid organ transplants who become pregnant represent an obstetrically high-risk population. Preconception planning and effective contraception tailored to the individual patient are critical in this group. Planned pregnancies improve both maternal and neonatal outcomes and provide a window of opportunity to mitigate risk and improve lifelong health. Optimal management of these pregnancies is not well defined. Common pregnancy complications after transplantation include hypertension, preterm birth, infection, and metabolic disease. Multidisciplinary preconception and prepartum management, and counseling decrease complications and benefit the maternal-neonatal dyad.

Residual Perchloroethylene in Dry-Cleaned Acetate: The Effect of Pressing and Extent of Inter-Dry-Cleaner Variability.

Measurements of residual perchloroethylene (PCE), a dry-cleaning solvent associated with human health effects, were made in dry-cleaned acetate cloth to enable improved characterizations of both occupational and environmental exposure. A limited sample size (25 acetate cloths) was used to explore the extent of inter-dry-cleaner variability in residual PCE and to characterize the effect of the pressing operation on residual PCE. A new method, which uses carbon-disulfide as the direct extracting agent, proved effective in the analysis of residual PCE, with a recovery-efficiency ≈ 75%. Inter-dry-cleaner variability of residual PCE, although marginally statistically significant, was relatively low, showing only a fourfold range compared to a 5-order-of-magnitude range obtained from Kawauchi and Nishiyama1. Pairwise comparison of residual PCE in nonpressed versus pressed acetate samples revealed a statistically significant reduction (p < 0.008), which amounted to a consistent (among dry-cleaners) pressing-related removal efficiency of 75 ± 4%. A preliminary assessment of the source term associated with the pressing operation (mass PCE liberated per kg cloth dry-cleaned, SPCE ≈ 30 mg/kg) indicates a minor contribution to the average ambient air concentrations within dry-cleaning establishments.