Fig. 4: Ex vivo uterus retains uterine components with 3D architecture and captures the features of implantation. | Nature Communications

Fig. 4: Ex vivo uterus retains uterine components with 3D architecture and captures the features of implantation.

From: An ex vivo uterine system captures implantation, embryogenesis, and trophoblast invasion via maternal-embryonic signaling

Fig. 4

A A representative 3D image of whole-mount immunofluorescence for FOXA2, a marker of uterine glands as well as embryonic PrE. See also Movie S6. B Representative 3D images of whole-mount immunofluorescence for CD45 and F4/80, markers of leukocytes and macrophages, respectively. White arrows indicate the presence of leukocytes and macrophages. See also Movie S7. C Slices from a representative 3D image of whole-mount immunofluorescence for a decidualization marker KLF5. White arrows indicate the induction of KLF5 in the embryo-attached subluminal stroma. Dotted line indicates the boundary between LE and stroma. D Representative 3D images of whole-mount immunofluorescence for FLK-1 and αSMA, markers of VE and VSM, respectively. White dotted areas indicate the avascular region in the vicinity of the embryo attachment site corresponding to in vivo implantation. See also Movie S8. E A slice from representative 3D images of whole-mount immunofluorescence for a proliferation marker Ki67. The cultured ex vivo uterus sustains an appropriate proliferation-differentiation switching (PDS) pattern, an index of uterine receptivity to the embryos. Note the cessation of proliferation in LE essential for ensuing trophoblast invasion. See also Movie S9. Dotted line indicates the boundary between LE and stroma. F Immunofluorescence of CK8 on histological sections at 36 h shows the onset of trophoblast invasion (arrowheads) into the stromal layer of the endometria. G A slice from a representative 3D image of whole-mount immunofluorescence for E-cadherin at 48 h shows the breach and elimination of uterine LE. tdTomato-negative uterine E-cadherin breaks at the boundary with the embryo indicated by white arrows. H H&E staining at 48 h exhibits enlarged nuclei in invading trophoblasts. White and orange dotted lines represent the surface of LE and the boundary between LE and stroma, respectively. PrE, primitive endoderm; Em, embryo; LE, luminal epithelium; GE, glandular epithelium; Str, stroma; Dec, decidua. DsRed2 or tdTomato indicates the mitochondria or cell membrane of all embryonic/extraembryonic cell lineages. Scale bars: 50 μm. Three independent experiments with different recipient animals were performed for all the data.

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