Pik3ca is required for mouse uterine gland development and pregnancy.

Eric Asselin,Hye Jin Chang,Jae-Wook Jeong,Tae Hoon Kim,Jean J Zhao,Un-Hwan Ha,Hee Sung Shin,Hanna E Teasley,Jung-Yoon Yoo

doi:10.1371/journal.pone.0191433

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 (Pgrcre/+Pik3caf/f; Pik3cad/d). A defect of uterine gland development and decidualization led to subfertility observed in Pik3cad/d mice. Pik3cad/d mice showed significantly decreased uterine weight compared to Pik3caf/f mice. Interestingly, a significant decrease of gland numbers were detected in Pik3cad/d mice compared to control mice. In addition, we found a decrease of Foxa2 expression, which is a known uterine gland marker in Pik3cad/d mice. Furthermore, the excessive proliferation of endometrial epithelial cells was observed in Pik3cad/d mice. Our studies suggest that Pik3ca has a critical role in uterine gland development and female fertility.

Highlights

The endometrial glands are critical for embryo-uterus communication, and their secretions are essential for blastocyst survival, development, and implantation [1,2,3]
There was a peak in Pik3ca expression at gestational day (GD) 2.5 and it sharply decreases at GD 3.5
The expression of Pik3ca was significantly increased at the time of implantation and continues to increase as pregnancy progresses indicating an important role for Pik3ca in pregnancy

Summary

Introduction

The endometrial glands are critical for embryo-uterus communication, and their secretions are essential for blastocyst survival, development, and implantation [1,2,3]. Adenogenesis, the uterine gland formation, is an important developmental process, which determines the receptivity of the adult uterus [3,4,5]. The organogenesis of mammals is usually established in utero. The mouse uterus develops from the Mullerian ducts during the fetal period, and uterine specific histology is completed in the postnatal period. The glands bud from the luminal epithelium.

Methods

Results

Conclusion