Pik3ca is required for mouse uterine gland development and pregnancy

Abstract

The PI3K/AKT signaling pathway plays a critical role in the maintenance of equilibrium between cell survival and apoptosis. The Pik3ca gene is mutated in a range of human cancers. It has been found to be oncogenic, and mutations lead to constitutive activation of the PI3K/AKT pathway. The expression patterns of PIK3CA proteins in the uterus of mice during early pregnancy indicate that it may play a role in the regulation of glandular epithelial cells, which is required to support uterine receptivity. To further investigate the role of Pik3ca in uterine function, Pik3ca was conditionally ablated only in the PGR-positive cells (Pgr(cre/+)Pik3ca(f/f); Pik3ca(d/d)). A defect of uterine gland development and decidualization led to subfertility observed in Pik3ca(d/d) mice. Pik3ca(d/d) mice showed significantly decreased uterine weight compared to Pik3ca(f/f) mice. Interestingly, a significant decrease of gland numbers were detected in Pik3ca(d/d) mice compared to control mice. In addition, we found a decrease of Foxa2 expression, which is a known uterine gland marker in Pik3ca(d/d) mice. Furthermore, the excessive proliferation of endometrial epithelial cells was observed in Pik3ca(d/d) mice. Our studies suggest that Pik3ca has a critical role in uterine gland development and female fertility.