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. 2017 Jan 24;96(2):313–326. doi: 10.1095/biolreprod.116.144410

Figure 9.

Figure 9.

Constitutive PGRA expression in the uterine epithelium inhibits LIF signaling, aberrantly promotes stromal hedgehog signaling, and causes the accumulation of fluid and solutes in the uterine lumen resulting in implantation failure. Left panel depicts normal embryo implantation occurring at the uterine epithelial surface on day 4.5 of pregnancy. The LIFR binds to LIF and activates downstream epithelial signaling promoting embryo attachment. Solute transporters for calcium (Ca+2), sodium (Na+), chlorine (Cl−), and water are increased at the epithelial surface causing a low-solute, high-water, and high-potassium (K+) level in the interstitial space. On the right panel within the Wnt7acre/+mPgrALsL/+mice, the LIFR and LIF are inhibited by high levels of epithelial PGRA. Additionally, PGRA promotes IHH, allowing for activation of hedgehog signaling within the stroma which can result in abnormal gland development and impaired decidualization. Solute and water transporters exhibit attenuation resulting in high levels of calcium (Ca+2), sodium (Na+), chlorine (Cl−), and water within the interstitial space. Potassium (K+) transporters are increased at the epithelial surface resulting in increased epithelial uptake. Therefore, high epithelial PGRA levels likely produce an unreceptive environment for embryo attachment. Epith = uterine epithelium.