HB-EGF regulates Prss56 expression during mouse decidualization via EGFR/ERK/EGR2 signaling pathway

Abstract

Embryo implantation and decidualization are key steps for successful reproduction. Although numerous factors have been identified to be involved in embryo implantation and decidualization, the mechanisms underlying these processes are still unclear. Based on our preliminary data, Prss56, a trypsin-like serine protease, is strongly expressed at implantation site in mouse uterus. However, the expression, regulation and function of Prss56 during early pregnancy are still unknown. In mouse uterus, is strongly expressed in the subluminal stromal cells at implantation site on day 5 of pregnancy compared to inter-implantation site. Under delayed implantation, expression is undetected. After delayed implantation is activated by estrogen, Prss56 is obviously induced at implantation site. Under artificial decidualization, Prss56 signal is seen at the primary decidual zone at the initial stage of artificial decidualization. When stromal cells are induced for decidualization, expression is significantly elevated. expression under decidualization is suppressed by siRNA. In cultured stromal cells, HB-EGF markedly stimulates expression through EGFR/ERK pathway. Based on promoter analysis, we also showed that Egr2 is involved in Prss56 regulation by HB-EGF. Collectively, expression at implantation site is modulated by HB-EGF/EGFR/ERK signaling pathway and involved in mouse decidualization.

Nucleolar stress regulation of endometrial receptivity in mouse models and human cell lines

“…The injections of ActD-soaked beads were performed as previously described 25,26 . Briefly, Affi-Gel Blue Gel Beads (#1537301, Bio-Rad, USA), which were approximately the size of a blastocyst, were washed three times with sterile Hanks’ balanced salt solution (HBSS, Sigma-Aldrich) and were then incubated with ActD (1 mM) in 30 μl 0.4% PVA (Sigma-Aldrich) at 37 °C for 3 h. Loaded beads (eight beads/ horn) were transferred into the uterine lumen of day 4 pseudopregnant mice.…”

Malic enzyme 1 is important for uterine decidualization in response to progesterone/cAMP/PKA/HB‐EGF pathway

“…[25][26][27][28] During in vitro decidualization, treatment with recombinant HB-EGF protein (rHB-EGF) significantly upregulated the expression of Me1, while silencing of HB-EGF by specific siRNA caused an obvious decline in HB-EGF expression as well as Me1 mRNA and protein levels ( Figure 9A-E). Since HB-EGF could also induce the differentiation of stromal cells, 29 we next tested whether Me1 was involved in the HB-EGF-mediated stromal differentiation. After transfection with Me1 siRNA, stromal cells were treated with rHB-EGF for 48 hours under in vitro decidualization.…”

“…HB-EGF, which is expressed in both the blastocyst and decidual cells, has been confirmed to be crucial for promoting embryo implantation and decidualization, and involving in the regulation of decidual related genes. [25][26][27][28][29] In uterine stromal cells, Me1 expression is regulated by HB-EGF. Progesterone could induce HB-EGF expression in rat or mouse uterine stromal cells.…”

Expression of proteins related to thyroid hormone function in the uterus is down‐regulated at the day of implantation in hypothyroid pregnant rats

“…Hypothyroidism-linked infertility could involve a defect in the expression of thyroid hormone receptor (TR), a protein that has been identified in rodent (Sayem et al, 2017) and human uteri (Aghajanova et al, 2011). There might also be a defect in the ERK1/2 signaling cascade in the uterus that participate in the thyroid hormone signaling (Liu et al, 2017) as well as a defect in the uterine expression of thyroid stimulating hormone receptor (TSHR), a protein that is reported to be present in the human and rodent endometrium (Colicchia et al, 2014;Sayem et al, 2017). There might also be a defect in the ERK1/2 signaling cascade in the uterus that participate in the thyroid hormone signaling (Liu et al, 2017) as well as a defect in the uterine expression of thyroid stimulating hormone receptor (TSHR), a protein that is reported to be present in the human and rodent endometrium (Colicchia et al, 2014;Sayem et al, 2017).…”

“…In addition, the defect in the expression of retinoic acid receptors (RARs), a protein that interacts with a specific DNA sequences, denoted as thyroid hormone responsive elements (TREs) (Lee and Privalsky, 2005), might also be the possible cause for hypothyroidism-related infertility, an these proteins have been identified in human (Cheng et al, 2008) and rat endometrium (Sayem et al, 2017). There might also be a defect in the ERK1/2 signaling cascade in the uterus that participate in the thyroid hormone signaling (Liu et al, 2017) as well as a defect in the uterine expression of thyroid stimulating hormone receptor (TSHR), a protein that is reported to be present in the human and rodent endometrium (Colicchia et al, 2014;Sayem et al, 2017). Based on these observations, the aims of this study were to identify changes in the expression of TRa and b, RAR, ERK1/2 and TSHR in the uterus at the time of implantation in hypothyroid condition and to observed the possibility that these proteins' levels could be restored towards normal following thyroxine treatment.…”