Figure 6.

Inhibition of E₂ hyper-sensitivity with ICI treatment rescues defective luminal closure and partially restores Rbpj^d/d mouse fertility. (A) Relative expression levels of E₂-regulated genes in day 4 uteri in Rbpj^f/f and Rbpj^d/d mice treated with a sesame oil vehicle or low-dose ICI. ICI, ICI 182780. The values are normalized to the GAPDH expression level and indicated as the mean ± SEM. n = 3. ^*P < 0.05, ^**P < 0.01. (B) Immunohistochemical staining of p-ERα and Ki-67 in vehicle- or ICI-treated Rbpj^d/d mice on day 4. The black arrows indicate positive signals. (C) Representative photos of immunofluorescence staining of untreated Rbpj^f/f, and vehicle- or ICI-treated Rbpj^d/d implantation sites on day 5. Similar results were obtained in 6 ICI-treated Rbpj^d/d mice. The white arrows denote extra epithelial folds. Cy3-labeled cytokeratin is shown in red; Hoechst 33342-labeled nuclei are shown in blue. (D) Representative uteri from Rbpj^f/f, Rbpj^d/d and ICI-treated Rbpj^d/d females on day 12. (E) Pregnancy outcomes in Rbpj^f/f, Rbpj^d/d and ICI-treated Rbpj^d/d females. (F) Average litter sizes in Rbpj^f/f, Rbpj^d/d and ICI-treated Rbpj^d/d females, ^*P < 0.05, ^**P < 0.01. Numbers within bars indicate the number of implantation sites/number of mice examined.