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

2017 ◽  
Vol 234 (3) ◽  
pp. 247-254 ◽  
Author(s):  
Jie Liu ◽  
Fei Gao ◽  
Yue-Fang Liu ◽  
Hai-Ting Dou ◽  
Jia-Qi Yan ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Stromal Cells ◽  
Embryo Implantation ◽  
Implantation Site ◽  
Mouse Uterus ◽  
Delayed Implantation ◽  
Initial Stage ◽  
And Function ◽  
Key Steps

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, Prss56 is strongly expressed in the subluminal stromal cells at implantation site on day 5 of pregnancy compared to inter-implantation site. Under delayed implantation, Prss56 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 in vitro decidualization, Prss56 expression is significantly elevated. Dtprp expression under in vitro decidualization is suppressed by Prss56 siRNA. In cultured stromal cells, HB-EGF markedly stimulates Prss56 expression through EGFR/ERK pathway. Based on promoter analysis, we also showed that Egr2 is involved in Prss56 regulation by HB-EGF. Collectively, Prss56 expression at implantation site is modulated by HB-EGF/EGFR/ERK signaling pathway and involved in mouse decidualization.

Inhibition of TMEM16A impedes embryo implantation and decidualization in mice

Reproduction ◽  
2018 ◽  
Author(s):  
Qianrong Qi ◽  
Yifan Yang ◽  
Kailin Wu ◽  
Qingzhen Xie
Keyword(s):  
Progesterone Receptor ◽  
Stromal Cells ◽  
Embryo Implantation ◽  
Mouse Uterus ◽  
Endometrial Stromal Cells ◽  
Uterine Endometrium ◽  
Molecule Inhibitor ◽  
Pathway Inhibition ◽  
And Function ◽  
Reproductive Processes

Recent studies revealed that TMEM16A is involved in several reproductive processes, including ovarian estrogen secretion and ovulation, sperm motility and acrosome reaction, fertilization, and myometrium contraction. However, little is known about the expression and function of TMEM16A in embryo implantation and decidualization. In this study, we focused on the expression and regulation of TMEM16A in mouse uterus during early pregnancy. We found that TMEM16A is up-regulated in uterine endometrium in response to embryo implantation and decidualization. Progesterone treatment could induce TMEM16A expression in endometrial stromal cells through progesterone receptor/c-Myc pathway, which is blocked by progesterone receptor antagonist or the inhibitor of c-Myc signaling pathway. Inhibition of TMEM16A by small molecule inhibitor (T16Ainh-A01) resulted in impaired embryo implantation and decidualization in mice. Treatment with either specific siRNA of Tmem16a or T16Ainh-A01 inhibited the decidualization and proliferation of mouse endometrial stromal cells. In conclusion, our results revealed that TMEM16A is involved in embryo implantation and decidualization in mice, compromised function of TMEM16A may lead to impaired embryo implantation and decidualization.

scholarly journals Differential expression and regulation of Cryab in mouse uterus during preimplantation period

Reproduction ◽  
2013 ◽  
Vol 145 (6) ◽  
pp. 577-585 ◽  
Author(s):  
Xue-Chao Tian ◽  
Qu-Yuan Wang ◽  
Dang-Dang Li ◽  
Shou-Tang Wang ◽  
Zhan-Qing Yang ◽  
...  
Keyword(s):  
Real Time ◽  
Stromal Cells ◽  
Real Time Pcr ◽  
Embryo Implantation ◽  
Mouse Uterus ◽  
High Level ◽  
Implantation Period

The aim of this study was to examine the expression and regulation of the crystallin, alpha B (Cryab) gene in mouse uterus during the peri-implantation period by in situ hybridization and real-time PCR. There was no detectable Cryab mRNA signal on days 1–4 of pregnancy. On day 5 of pregnancy when embryo implanted, a high level of Cryab mRNA signal was found in the subluminal stroma surrounding the implanting blastocyst. On days 6–8, Cryab mRNA was strongly expressed in the primary decidua. By real-time PCR, a high level of Cryab expression was detected on days 7 and 8 of pregnancy, although Cryab expression was seen from days 1 to 8. Under in vivo and in vitro artificial decidualization, Cryab expression was significantly elevated. Compared with the progesterone-primed delayed implantation uterus, a high level of Cryab mRNA expression was observed in estrogen-activated implantation uterus. In the uterine stromal cells, cAMP, estrogen, and progesterone could induce the expression of Cryab gene. In the ovariectomized mouse uterus, estrogen could also induce the expression of Cryab while progesterone inhibited its expression. Our data suggest that Cryab may play an important role during mouse embryo implantation and decidualization and that estrogen and progesterone can regulate the expression of Cryab gene.

scholarly journals Regulation and Function of Deiodinases During Decidualization in Female Mice

Endocrinology ◽  
2014 ◽  
Vol 155 (7) ◽  
pp. 2704-2717 ◽  
Author(s):  
Wen-Bo Deng ◽  
Xiao-Huan Liang ◽  
Ji-Long Liu ◽  
Zeng-Ming Yang
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Early Pregnancy ◽  
Stromal Cells ◽  
Mouse Uterus ◽  
Opposite Strand ◽  
And Function ◽  
Kinase A

Thyroid dysfunction during human pregnancy is closely related to serious pregnancy outcome. However, the regulation and function of thyroid hormones during early pregnancy are largely unknown. We found that type II deiodinase, an enzyme converting T4 to activated T3, is highly expressed in the mouse uterus on days 3 and 4 of pregnancy. Once the embryo implants into the receptive uterus, type III deiodinase (Dio3), a mainly paternally imprinted gene for inactivating T3, is significantly induced in the stromal cells and accompanied by DNA hypermethylation of intergenic differentially CpG methylation regions in the δ-like 1 homolog-Dio3 imprinting cluster. The concentration of uterine free T3 is actually decreased after embryo implantation. T3 induces Dio3 expression both in vivo and in vitro, suggesting a positive feedback loop. T3 addition or Dio3 knockdown compromises decidualization. These results indicate that the Dio3-mediated local T3 decrease is critical for decidualization of stromal cells during early pregnancy. Furthermore, we found that progesterone regulates Dio3 expression through its cognate receptor both in vivo and in vitro. Additionally, cAMP regulates Dio3 transcription through the protein kinase A-cAMP response element-binding protein pathway. The inhibition of the protein kinase A pathway results in decreased Dio3 expression and impaired decidualization. Dio3 opposite strand (Dio3os) expressed in a similar pattern to Dio3, is transcribed from the opposite strand of Dio3 and fine-tunes Dio3 expression during decidualization. Our data indicate that Dio3 is strongly expressed and tightly controlled during decidualization.

Increased Expression of NDRG3 in Mouse Uterus During Embryo Implantation and in Mouse Endometrial Stromal Cells During In Vitro Decidualization

2017 ◽  
Vol 25 (8) ◽  
pp. 1197-1207 ◽  
Author(s):  
Qian Yang ◽  
Xuan Zhang ◽  
Yan Shi ◽  
Ya-Ping He ◽  
Zhao-Gui Sun ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Embryo Implantation ◽  
Mouse Uterus ◽  
Endometrial Stromal Cells

scholarly journals Basigin-Mediated Gene Expression Changes in Mouse Uterine Stromal Cells During Implantation

Endocrinology ◽  
2009 ◽  
Vol 150 (2) ◽  
pp. 966-976 ◽  
Author(s):  
Li Chen ◽  
Robert J. Belton ◽  
Romana A. Nowak
Keyword(s):  
Gene Expression ◽  
Stromal Cells ◽  
Stromal Cell ◽  
Embryo Implantation ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Mouse Uterus ◽  
Spatial Regulation ◽  
Proliferation And Differentiation ◽  
Stromal Cell Culture

Implantation of mouse embryos is dependent on the proliferation and differentiation of uterine stromal cells in a process called decidualization. Decidualization both supports and limits the invasion of the implanting embryo and is regulated in part by the expression of matrix metalloproteinases (MMPs) and their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs). Molecules that alter the balance between MMP and TIMP expression could prevent implantation of the embryo. The membrane glycoprotein basigin (CD147/EMMPRIN), a known inducer of MMPs, is necessary for normal implantation in the mouse. The purpose of this study was to investigate the potential roles of basigin during implantation in the mouse. Using an in vitro stromal cell culture system, we found that recombinant human basigin protein (rBSG) increases MMP-3 and MMP-9 expression without altering TIMP-3 expression. Our results also showed rBSG induces expression of cytokines IL-1α/β and leukocyte chemoattractants, CCL3, CCL20, CXCL2, and CXCL5. More importantly, rBSG significantly suppressed stromal cell decidualization as shown by the inhibition of alkaline phosphatase-2 expression and activity by rBSG. However, rBSG did not affect stromal cell proliferation. Taken together, our data indicate that basigin mediates gene expression changes in mouse uterine stromal cells and suggests that temporal and spatial regulation of basigin expression may be involved in the recruitment of leukocytes to the mouse uterus during early pregnancy. The role of basigin during embryo implantation in mice is examined. Basigin regulates matrix metalloproteinase, IL-1, and leukocyte chemoattractant production by uterine stromal cells.

scholarly journals Decidual expression and regulation of Fatty acid desaturase 3 during mouse decidualization

Reproduction ◽  
2018 ◽  
Author(s):  
Shuai Lin ◽  
Yu-Yuan Zhu ◽  
Wei Hu ◽  
Yan Yang ◽  
Jia-Mei Luo ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Stromal Cells ◽  
Fatty Acid Biosynthesis ◽  
Fatty Acid Desaturase ◽  
Expression Regulation ◽  
Implantation Site ◽  
Estrogen Regulation ◽  
Delayed Implantation ◽  
Ovariectomized Mice ◽  
And Function

Decidualization is required for the successful establishment of pregnancy in rodents and primates. Fatty acid desaturase 3 (Fads3) belongs to the fatty acid desaturase family, which is a crucial enzymes for highly unsaturated fatty acid biosynthesis. However, the expression, regulation and function of Fads3 during early pregnancy in mice are still unknown. In this study, we examined Fads3 expression, regulation and function during mouse decidualization. The expression of Fads3 is detected in the subluminal stromal cells at implantation site on day 5 of pregnancy, but not at inter-implantation site and in day 5 pseudopregnant uteri. Compared to delayed implantation, Fads3 is strongly expressed after delayed implantation is activated by estrogen treatment. From days 6 to 8, Fads3 mRNA signals are significantly detected in the decidua. In ovariectomized mice, estrogen significantly stimulates Fads3 expression. However, estrogen has no effect on Fads3 expression in ovariectomized ERα deficient mice, suggesting that estrogen regulation on Fads3 expression is ERα-dependent. When ovariectomized mice were treated with progesterone, Fads3 expression is significantly increased by progesterone. Progesterone stimulation on Fads3 expression is also detected in cultured stromal cells, which is abrogated by RU486 treatment. These data indicate that progesterone upregulation on Fads3 expression is progesterone receptor-dependent. Fads3 knockdown by siRNA reduces in vitro decidualization of mouse stromal cells. Taken together, Fads3 may play an important role during mouse decidualization.

scholarly journals Regulation and Function of Laminin A5 during Mouse and Human Decidualization

2021 ◽  
Vol 23 (1) ◽  
pp. 199
Author(s):  
Zhen-Shan Yang ◽  
Hai-Yang Pan ◽  
Wen-Wen Shi ◽  
Si-Ting Chen ◽  
Ying Wang ◽  
...  
Keyword(s):  
Early Pregnancy ◽  
Stromal Cells ◽  
Basement Membranes ◽  
Pivotal Role ◽  
Cellular Phenotype ◽  
Mouse Uterus ◽  
Endometrial Stromal Cells ◽  
And Function

Decidualization is essential to the establishment of pregnancy in rodents and primates. Laminin A5 (encoding by Laminin α5) is a member of the laminin family, which is mainly expressed in the basement membranes. Although laminins regulate cellular phenotype maintenance, adhesion, migration, growth, and differentiation, the expression, function, and regulation of laminin A5 during early pregnancy are still unknown. Therefore, we investigated the expression and role of laminin A5 during mouse and human decidualization. Laminin A5 is highly expressed in mouse decidua and artificially induced deciduoma. Laminin A5 is significantly increased under in vitro decidualization. Laminin A5 knockdown significantly inhibits the expression of Prl8a2, a marker for mouse decidualization. Progesterone stimulates the expression of laminin A5 in ovariectomized mouse uterus and cultured mouse stromal cells. We also show that progesterone regulates laminin A5 through the PKA-CREB-C/EBPβ pathway. Laminin A5 is also highly expressed in human pregnant decidua and cultured human endometrial stromal cells during in vitro decidualization. Laminin A5 knockdown by siRNA inhibits human in vitro decidualization. Collectively, our study reveals that laminin A5 may play a pivotal role during mouse and human decidualization via the PKA-CREB-C/EBPβ pathway.

scholarly journals Sperm modulate uterine immune parameters relevant to embryo implantation and reproductive success in mice

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
John E. Schjenken ◽  
David J. Sharkey ◽  
Ella S. Green ◽  
Hon Yeung Chan ◽  
Ricky A. Matias ◽  
...  
Keyword(s):  
Reproductive Success ◽  
Seminal Fluid ◽  
Embryo Implantation ◽  
Reproductive Investment ◽  
Global Gene Expression ◽  
Wild Type ◽  
Mouse Uterus ◽  
Immune Parameters ◽  
Oocyte Fertilization

AbstractSeminal fluid factors modulate the female immune response at conception to facilitate embryo implantation and reproductive success. Whether sperm affect this response has not been clear. We evaluated global gene expression by microarray in the mouse uterus after mating with intact or vasectomized males. Intact males induced greater changes in gene transcription, prominently affecting pro-inflammatory cytokine and immune regulatory genes, with TLR4 signaling identified as a top-ranked upstream driver. Recruitment of neutrophils and expansion of peripheral regulatory T cells were elevated by seminal fluid of intact males. In vitro, epididymal sperm induced IL6, CXCL2, and CSF3 in uterine epithelial cells of wild-type, but not Tlr4 null females. Collectively these experiments show that sperm assist in promoting female immune tolerance by eliciting uterine cytokine expression through TLR4-dependent signaling. The findings indicate a biological role for sperm beyond oocyte fertilization, in modulating immune mechanisms involved in female control of reproductive investment.

scholarly journals Bu Shen Zhu Yun Decoction Improves Endometrial Receptivity via VEGFR-2-Mediated Angiogenesis

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Li Li ◽  
Huabo Jiang ◽  
Xuecong Wei ◽  
Dandan Geng ◽  
Ming He ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Embryo Implantation ◽  
Mapk Signaling ◽  
Endometrial Receptivity ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Cell Counting ◽  
Nuclear Antigen ◽  
Vitro Fertilization

Vascular endothelial growth factor receptor-2 (VEGFR-2) regulates the mitogen-activated protein kinase (MAPK) signaling pathway and plays an important role in angiogenesis. Bu Shen Zhu Yun decoction (BSZYD) can improve endometrial receptivity and embryo implantation rates in patients undergoing in vitro fertilization. However, whether BSZYD improves endometrial receptivity via angiogenesis remains unclear. Here, we investigated the effects of BSZYD on the proliferation, migration, and angiogenesis of human endometrial microvascular endothelial cells (HEMECs) and found that BSZYD upregulated the expression of cyclin D1, matrix metalloproteinase 9 (MMP9), and proliferating cell nuclear antigen (PCNA) in HEMECs. Cell Counting Kit 8 assay, scratch-wound assay, and Tube Formation Assay results showed that BSZYD promoted the proliferation, migration, and angiogenesis of HEMECs. Western blot analysis results revealed the activation of the MAPK signaling pathway by BSZYD through the upregulation of VEGF and VEGFR-2 expression. Together, these findings highlight the novel mechanism underlying BSZYD-mediated improvement in endometrial receptivity through the MAPK signaling pathway.

scholarly journals Differential expression and regulation of Tdo2 during mouse decidualization

2013 ◽  
Vol 220 (1) ◽  
pp. 73-83 ◽  
Author(s):  
Dang-Dang Li ◽  
Ying-Jie Gao ◽  
Xue-Chao Tian ◽  
Zhan-Qing Yang ◽  
Hang Cao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Differential Expression ◽  
Stromal Cells ◽  
Real Time Pcr ◽  
Mouse Uterus ◽  
Decidual Cells ◽  
High Level ◽  
Rate Limiting

Tryptophan 2,3-dioxygenase (Tdo2) is a rate-limiting enzyme which directs the conversion of tryptophan to kynurenine. The aim of this study was to examine the expression and regulation of Tdo2 in mouse uterus during decidualization. Tdo2 mRNA was mainly expressed in the decidua on days 6–8 of pregnancy. By real-time PCR, a high level of Tdo2 expression was observed in the uteri from days 6 to 8 of pregnancy, although Tdo2 expression was observed on days 1–8. Simultaneously, Tdo2 mRNA was also detected under in vivo and in vitro artificial decidualization. Estrogen, progesterone, and 8-bromoadenosine-cAMP could induce the expression of Tdo2 in the ovariectomized mouse uterus and uterine stromal cells. Tdo2 could regulate cell proliferation and stimulate the expression of decidual marker Dtprp in the uterine stromal cells and decidual cells. Overexpression of Tdo2 could upregulate the expression of Ahr, Cox2, and Vegf genes in uterine stromal cells, while Tdo2 inhibitor 680C91 could downregulate the expression of Cox2 and Vegf genes in uterine decidual cells. These data indicate that Tdo2 may play an important role during mouse decidualization and be regulated by estrogen, progesterone, and cAMP.

Sign in / Sign up

Export Citation Format

Share Document