Uterine Micro-Environment and Estrogen-Dependent Regulation of Osteopontin Expression in Mouse Blastocyst

Qing-Zhen Xie,Wang-Ming Xu,Qian-Rong Qi,Jing Yang,Ying-Xian Chen,Qian Liu

doi:10.3390/ijms140714504

Abstract

Embryo implantation is a highly synchronized bioprocess between an activated blastocyst and a receptive uterus. In mice, successful implantation relies on the dynamic interplay of estrogen and progesterone; however, the key mediators downstream of these hormones that act on blastocyst competency and endometrium receptivity acquisition are largely unknown. In this study, we showed that the expression of osteopontin (OPN) in mouse blastocysts is regulated by ovarian estrogen and uterine micro-environment. OPN mRNA is up-regulated in mouse blastocyst on day 4 of pregnancy, which is associated with ovarian estrogen secretion peak. Hormone treatment in vivo demonstrated that OPN expression in a blastocyst is regulated by estrogen through an estrogen receptor (ER). Our results of the delayed and activated implantation model showed that OPN expression is induced after estrogen injection. While estrogen treatment during embryo culture in vitro showed less effect on OPN expression, the tubal ligation model on day 3 of pregnancy confirmed that the regulation of estrogen on OPN expression in blastocyst might, through some specific cytokines, have existed in a uterine micro-environment. Collectively, our study presents that estrogen regulates OPN expression and it may play an important role during embryo implantation by activating blastocyst competence and facilitating the endometrium acceptable for active blastocyst.

Highlights

In mammals, embryo implantation occurs in a limited time known as the window of implantation, the time after ovulation and the full formation of the corpus luteum [1]
The delayed implantation model could be induced by ovariectomy on the morning of day 4 before the estrogen secretion peak, the embryo will enter into a quiescent state which could be maintained for few days under the condition of continuing progesterone treatment
Was greater than that from 08:00 (Figure 1B(d–f)). These findings demonstrated that OPN mRNA and protein are highly expressed in mouse blastocyst on day 4, the OPN expression pattern corresponds to the secretion pattern of ovarian estrogen

Summary

Introduction

Embryo implantation occurs in a limited time known as the window of implantation, the time after ovulation and the full formation of the corpus luteum [1]. The secretion of progesterone is stimulated by mating behavior and the formation of corpora luteum, and gradually increases during the progress of pregnancy, while the ovarian estrogen has two secreted peaks at the proestrous phase and pre-implantation phase on day 4 of pregnancy (day of vaginal plug as day 1). Embryo implantation will occur appropriately if the ovariectomy is performed after the estrogen secretion peak [8]. Such a delayed-activated implantation model demonstrated that pre-implantation estrogen mainly interacts with its receptor α (ERα) and directs successful implantation in a progesterone primed endometrium. The finding that ER protein was localized in mouse blastocyst during implantation [10] indicates that estrogen may directly regulate the gene expression in blastocyst via binding to ERα

Results

Discussion

Conclusion