Fig. 6: Shared signaling pathways between Smad1/5 cKO and Acvr2a cKO mice reveal abnormal retention of apicobasal polarity and defective endometrial receptivity.

a–b Volcano plots of differentially expressed transcripts determined by RNAseq between control vs. Smad1/5 cKO (a) and control vs. Acvr2a cKO (b) in the uterine tissues of 3.5 dpc pseudopregnant mice. Red, upregulated (fold change >1.4, p < 0.01 by paired, two-tailed, t test); blue, downregulated (<0.6, p < 0.01); labeled genes share differential expression in both genotypes. c Gene ontology classification of the shared genes in Smad1/5 cKO and Acvr2a cKO mice that are differentially expressed vs. controls. Bubble size and colors are plotted relative to p values, whereas the location in the scatterplot represents functional categorization. d Scanning electron microscopy analysis of the surface of the luminal uterine epithelium of 3.5 dpc control, Smad1/5 cKO, and Acvr2a cKO mice. Size bars = 10 µm (left) or 2 µm (right). Images in d are representative images obtained from analyses of three samples per genotype. e–j Immunofluorescence of the uterus of control (e–f), Smad1/5 cKO (g–h) and Acvr2a cKO (i–j) mice at 3.5 dpc of pseudopregnancy. Tissues were stained with E-cadherin (red), vimentin (green), and DAPI (white), e, g, i are confocal z-stacks; f, h, j, are 3D-renderings of the z-stacks. Yellow arrows in the control uterus (f) indicate that E-cadherin immunoreactivity was decreased in the basal region of the luminal epithelium of control mice but maintained in the Smad1/5 cKO (h) and Acvr2a cKO (j) mice. Size bars are 20 µm. e–j are representative images of at least three samples analyzed per genotype. k Schematic of the BMP signaling pathway that is active during the window of implantation.