Fig. 4: Rescue of implantation defect and recovery of aberrant activated epithelial cells proliferation and ESR signaling in Mig-6^d/d mice by Erbb2 double ablation.

a Uteri of control, Mig-6^d/d, Mig-6^d/dErbb2^d/d, and Erbb2^d/d mice and number of implantation sites at GD 5.5 (n = 4 for each genotype). Data are represented as mean ± SEM, * p < 0.0001 by Ordinary one-way ANOVA test. Scale bars: 1 cm. b Hematoxylin and eosin (H&E) staining in paired endometrium of control, Mig-6^d/d, Mig-6^d/dErbb2^d/d, and Erbb2^d/d mice at GD 5.5. Arrowheads indicate embryos. Scale bars: 200 μm for (i), (iii), (v), and (vii) and 50 μm for (ii), (iv), (vi), and (viii). c Immunohistochemistry analysis of Ki67 and Cyclin D1 in the endometrium of control, Mig-6^d/d, Mig-6^d/dErbb2^d/d, and Erbb2^d/d mice at GD 3.5. Scale bars: 50 μm. d, e RT-qPCR analysis of Muc1 (* p = 0.00156, ** p = 0.0091, and ** p = 0.0029), Clca3(*** p < 0.0001), Ltf (*** p < 0.0001), and C3 (*** p = 0.0007, *** p = 0.0003, and *** p < 0.0001). Data are represented as mean ± SEM and analyzed by Ordinary one-way ANOVA test. (d) and immunohistochemistry analysis of MUC1 and LTF (e) as epithelial ESR1 target genes in the uterus of control, Mig-6^d/d, Mig-6^d/dErbb2^d/d, and Erbb2^d/d mice at GD 3.5 (n = 5 for each genotype). Scale bars: 50 μm. Three independent experiments were performed for a - e with similar results. Source data are provided in the Source Data file.