Using Comparative Transcriptomics and Histology to Identify Significant Differentially Expressed Genes Associated with Retained Placenta in Humans and Rhesus Macaques (Macaca mulatta)
Retained placenta is an important reproductive complication that affects humans and nonhuman primates (NHPs). Accurate prediction of retained placenta in both species is a current challenge because the etiology is unknown, biomarkers are inadequate, and data are heterogeneous. Through a comparative approach, this study identifies 34 significantly differentially expressed genes associated with retained placenta shared between humans and NHPs. Pathway enrichment revealed upregulation in innate and adaptive immunity in addition to pathways related to hemostasis. Retained placentas in NHPs had higher histologic evidence of inflammation as compared with human samples. These cross-species transcriptional results can serve as an initial step to guide NHP refinement as a model system and inform retained placenta biomarker discovery in both humans and NHPs.
Representative H&E slides of controls and cases. (A) Third-trimester placenta from a 32-y-old woman. Placental layers include decidua, trophoblastic shell, villi, and chorionic membrane. No myometrium is present on the slide since it was an uncomplicated birth. 5× original magnification. (B) Retained placenta from a woman. 5× original magnification. Inset shows syncytial knots and villus hypoplasia, often observed in retained placentas. 200× original magnification. (C) Third-trimester control NHP placenta from a 4-y-old rhesus macaque, showing multiple intact layers, including the myometrium, decidua, trophoblastic shell, villi, and chorionic membrane. 6× original magnification. (D) Retained placenta from a NHP with areas of inflammation. 4× original magnification. Inset shows an area of suppurative inflammation with colonies of bacterial rods within the placental membranes. 200× original magnification. All images are of routine H&E stains.
Voronoi visualization created using Reactome Knowledgebase52,53 of overrepresented pathways for all shared retained placenta genes using the full RNA dataset. Yellow corresponds to pathways associated with upregulated expression, and blue corresponds to pathways associated with downregulated expression.
Voronoi visualization created using Reactome Knowledgebase52,53 of overrepresented pathways for the 17 upregulated significant DEGs. Pathways in yellow are those that are overrepresented in gene set analysis. Gradation of yellow corresponds to P value of overlap significance. Note dissolution of fibrin clot pathway highlighted in yellow in the category of hemostasis (bottom left).
Voronoi visualization created using Reactome Knowledgebase52,53 of overrepresented pathways for the 17 downregulated significant DEGs. Pathways in yellow are those that are overrepresented in gene set analysis. Gradation of yellow corresponds to P value of overlap significance. Note the Tie2 signaling pathway highlighted in yellow in the category of hemostasis (middle left).
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