Expression, regulation and function of Egr1 during implantation and decidualization in mice

Abstract

Early growth response gene 1 (Egr1), a zinc finger transcriptional factor, plays an important role in regulating cell proliferation, differentiation and angiogenesis. Current data have shown that Egr1 is involved in follicular development, ovulation, luteinization and placental angiogenesis. However, the expression, regulation and function of Egr1 in mouse uterus during embryo implantation and decidualization are poorly understood. Here we showed that Egr1 was strongly expressed in the subluminal stroma surrounding the implanting blastocyst on day 5 of pregnancy. Injection of Egr1 siRNA into the mouse uterine horn could obviously reduce the number of implanted embryos and affect the uterine vascular permeability. Further study found that Egr1 played a role through influencing the expression of cyclooxygenase-2 (Cox-2), microsomal prostaglandin E synthase 1 (mPGES-1), vascular endothelial growth factor (Vegf), transformation related protein 53 (Trp53) and matrix metallopeptidase 9 (Mmp9) genes in the process of mouse embryo implantation. Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) might direct the expression of Egr1 in the uterine stromal cells. Under in vivo and in vitro artificial decidualization, Egr1 expression was significantly decreased. Overexpression of Egr1 downregulated the expression of decidual marker decidual/trophoblast PRL-related protein (Dtprp) in the uterine stromal cells, while inhibition of Egr1 upregulated the expression of Dtprp under in vitro decidualization. Estrogen and progesterone could regulate the expression of Egr1 in the ovariectomized mouse uterus and uterine stromal cells. These results suggest that Egr1 may be essential for embryo implantation and decidualization.

Krüppel-Like Factor 13 Deficiency in Uterine Endometrial Cells Contributes to Defective Steroid Hormone Receptor Signaling but Not Lesion Establishment in a Mouse Model of Endometriosis1

“…In contrast, KLF13 loss did not affect Esr2 expression and preferentially diminished Pgr-b rather than Pgr-a, expression, the latter based on the comparable reductions in total Pgr and Pgr-b transcripts. The functional consequence of the distinct changes in Pgr-a vs. Pgr-b in Klf13 null vs Klf9 null lesions is convincingly illustrated by the contrasting effects elicited by Klf9 and Klf13 null mutations (relative to WT) on the expression of the same PGR target genes (Wnt1, Wnt4, Dkk1, Egr1) [37][38][39][40] and is consistent with the opposing transactivities of PGR-A and PGR-B isoforms [41]. However, since P 4 -regulated genes may also be direct or indirect E 2 -target genes (e.g.…”

Hmgn1 acts downstream of C/EBPβ to regulate the decidualization of uterine stromal cells in mice

“…18 As the progression of decidualization was increasing, Hmgn1 expression was gradually enhanced and reached a peak at 96 h (Fig. 4C).…”

“…Hybridization was performed as described previously. 18 Sections were counterstained with 1% methyl green. The positive signal was visualized as a dark brown color.…”

“…18 Briefly, uterine stromal cells were induced for in vitro decidualization with fresh medium supplemented with progesterone (1 mM) and estradiol-17b (10 nM) in DMEM-F12 with 2% charcoaltreated FBS (Biological Industries Ltd., Kibbutz Beit Hemeek, Israel).…”

Age-associated up-regulation of EGR1 promotes granulosa cell apoptosis during follicle atresia in mice through the NF-κB pathway

“…17 In the reproductive system, it has been reported that knockout of EGR1 can lead to female infertility through its regulation of LH-b transcription in mice, 18 and EGR1 may be essential for embryo implantation and decidualization in mice. 19 However, there is no direct evidence that EGR1 participates in GC apoptosis and follicle atresia during ovarian aging. The aims of this study were to investigate the expression manner of EGR1 in the mouse ovary and to explore the EGR1 regulated signaling pathway involved in GC apoptosis.…”