Estrogen induces EGR1 to fine‐tune its actions on uterine epithelium by controlling PR signaling for successful embryo implantation

作者：Hye‐Ryun Kim, Yeon Sun Kim, Jung Ah Yoon, Seung Chel Yang, Mira Park, Dong‐Won Seol, Sang Woo Lyu, Jin Hyun Jun, Hyunjung Jade Lim, Dong Ryul Lee, Haengseok Song · 发表于：The FASEB Journal · 年份：2017 · DOI：10.1096/fj.201700854rr · 被引用次数：49 · 研究领域：Reproductive System and Pregnancy、Endometriosis Research and Treatment、Uterine Myomas and Treatments

The harmonized actions of ovarian E 2 and progesterone (P 4 ) regulate the proliferation and differentiation of uterine cells in a spatiotemporal manner. Imbalances between these hormones often lead to infertility and gynecologic diseases. Whereas numerous factors that are involved in P 4 signaling have been identified, few local factors that mediate E2 actions in the uterus have been revealed. Here, we demonstrate that estrogen induces the transcription factor, early growth response 1 ( Egr1 ), to fine‐tune its actions in uterine epithelial cells (ECs) that are responsible for uterine receptivity for embryo implantation. In the presence of exogenous gonadotrophins, ovulation, fertilization, and embryonic development normally occur in Egr1 −/− mice, but these animals experience the complete failure of embryo implantation with reduced artificial decidualization. Although serum levels of E 2 and P 4 were comparable between Egr1 +/+ and Egr1 −/− mice on d 4 of pregnancy, aberrantly reduced levels of progesterone receptor in Egr1 −/− uterine ECs caused enhanced E 2 activity and impaired P 4 response. Ultra‐ structural analyses revealed that Egr1 −/− ECs are not fully able to provide proper uterine receptivity. Uterine mRNA landscapes in Egr1 −/− mice revealed that EGR1 controls the expression of a subset of E 2 ‐regulated genes. In addition, P 4 signaling was unable to modulate estrogen actions, including those that are involved in cell‐cycle progression, in ECs that were deficie...