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. 2023 Mar 1;14:1174. doi: 10.1038/s41467-023-36740-5

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 5 — a Diagram of the fine-structural organization of the mouse placental labyrinth, which forms the feto-maternal exchange area. EC = endothelial cells; SynT-I = syncytiotrophoblast layer I; SynT-II = syncytiotrophoblast layer II; sTGC = sinusoidal trophoblast giant cell; mat. blood = maternal blood. b LacZ staining of an Atp11a^+/− placenta in which LacZ serves as readout of endogenous Atp11a expression. Atp11a expression locates to the syncytiotrophoblast, whereas endothelial cells (EC) lining fetal blood (f) vessels and sinusoidal trophoblast giant cells (sTGCs) facing maternal blood (m) sinusoids are not stained. Staining is representative of n = 6 placentas. c Double immunofluorescence staining for beta-galactosidase as indicator of ATP11A expression (green) and for MCT4 (red) as marker of the syncytiotrophoblast layer-II (SynT-II). The closely juxtaposed but non-overlapping staining (yellow rectangle) demonstrates that ATP11A is confined to SynT-I. The arrowhead points to an sTGC negative for ATP11A. Stainings are representative of n = 3 placentas. d MCT1/MCT4 double immunofluorescence staining on Atp11a WT and KO placentas, imaged at identical exposure setting. Asterisks demarcate areas of severe vascular disruptions. MCT4 staining intensity is increased, but MCT1 staining decreased in Atp11a mutant placentas. The SynT-II layer labeled by MCT4 is also increased in thickness, often delaminated from the SynT-I layer (inset) and exhibits pathological accumulations (yellow arrows). Images are representative of n ≥ 3 samples per genotype. e Virtual deconvolution of placental RNA-seq data for cell type-specific composition^39,40 reveals an under-representation of mature SynT-I, glycogen cells (GCs) and spongiotrophoblast (SpT) cells, but an enrichment of precursors (prec) of SynT-I, SynT-II, and GCs in Atp11a-mutant placentas. Each bar represents an individual placenta, with absolute values of the proportional cell type composition being depicted. Statistically significant cell type differences are given on the right; comparisons were made with a two-tailed Student’s t test. All p values are provided in Supplementary Data 1. JZP = junctional zone precursor, LaTP = Labyrinth precursor (WT n = 6, HET n = 8, KO n = 7). Source data are provided as a Source Data file.