Fig. S1.

Progesterone supplementation failed to restore embryo implantation in Shp2^d/d mice. (A) Serum estradiol-17β (E₂) level in Shp2^f/f and Shp2^d/d mice on day 4 (D4) of pregnancy. (B) Serum progesterone (P₄) level in Shp2^f/f and Shp2^d/d mice on D4 of pregnancy. Data are means ± SEM (*P < 0.05; Student’s t test). Numbers within bars indicate numbers of mice examined. (C) Immunohistochemistry staining of 3β-hydroxysteroid dehydrogenase II (3β-HSDII) and P450 cholesterol side-chain cleavage enzyme (P450scc) in Shp2^f/f and Shp2^d/d D4 ovaries. CL, corpus luteum; F, follicle. (Scale bars, 100 μm.) (D) Embryo implantation status of Shp2^d/d mice as revealed by blue dye method on D6 of pregnancy after receiving daily P₄ supplementation (2 mg per mouse) from D3–5. Black arrow indicates the embryos in the right panel are recovered from the corresponding uteri. (E) Real-time PCR analysis of the uterine receptivity marker genes on D4 after P₄ supplementation. The values are normalized to the Gapdh expression level and indicated as the mean ± SEM, n = 3. **P < 0.01. (F) Immunohistochemical staining of Ki-67 in Shp2^f/f and Shp2^d/d in D4 uteri. (Scale bar, 100 μm.) Ge, glandular epithelium; Le, luminal epithelium; S, stroma.