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Loss- and Gain-of-function Approach to Investigate Early Cell Fate Determinants in Preimplantation Mouse Embryos
Published on: June 6, 2016
GRIM-19, a gene associated with retinoid-interferon-induced mortality, affects endometrial receptivity and embryo
Yang Yang1, Yanyan Sun1, Laiyang Cheng1
1Infertility Center, Qilu Hospital, Shandong University, 107 West Wenhua Road, Jinan, Shandong, 250012, China.
Abstract:
GRIM-19 is associated with apoptosis, abnormal proliferation, immune tolerance and malignant transformation, and it also plays an important role in early embryonic development. Although the homologous deletion of GRIM-19 causes embryonic lethality in mice, the precise role of GRIM-19 in embryo implantation has not been elucidated. Here we show that GRIM-19 plays an important role in endometrial receptivity and embryo implantation. Day 1 to Day 6 pregnant mouse uteri were collected. Immunohistochemistry studies revealed the presence of GRIM-19 on the luminal epithelium and glandular epithelium throughout the implantation period in pregnant mice. The protein and mRNA levels of GRIM-19 were markedly decreased on Day 4 of pregnancy in pregnant mice, but there was no change in GRIM-19 levels in a group of pseudopregnant mice. Overexpression of GRIM-19 decreased the adhesion rate of RL95-2-BeWo co-cultured spheroids and increased apoptosis. Furthermore, STAT3 and IL-11 mRNA and protein levels were reduced by overexpressing GRIM-19, but protein and mRNA levels of TNF-α were increased. These findings indicate the involvement of GRIM-19 in the embryo implantation process by regulating adhesion, apoptosis and immune tolerance.
Insights
The gene GRIM-19 is crucial for embryo implantation and endometrial receptivity. Its downregulation on day 4 of pregnancy impacts embryo adhesion, apoptosis, and immune tolerance, highlighting its role in successful pregnancy.
Area of Science:
- Reproductive Biology
- Developmental Biology
- Molecular Biology
Background:
- GRIM-19 is linked to apoptosis, proliferation, immune tolerance, and cancer.
- While GRIM-19 deficiency causes embryonic lethality, its specific role in implantation is unclear.
Purpose of the Study:
- To investigate the role of GRIM-19 in endometrial receptivity and embryo implantation.
- To elucidate the molecular mechanisms by which GRIM-19 influences implantation.
Main Methods:
- Immunohistochemistry to detect GRIM-19 expression in pregnant mouse uteri.
- Analysis of GRIM-19 protein and mRNA levels during early pregnancy.
- In vitro studies using cell lines to assess the impact of GRIM-19 overexpression on adhesion and apoptosis.
Main Results:
- GRIM-19 is present in the uterine epithelium during implantation.
- GRIM-19 levels decrease significantly on day 4 of pregnancy in pregnant mice.
- Overexpression of GRIM-19 reduces embryo spheroid adhesion, increases apoptosis, and alters levels of STAT3, IL-11, and TNF-α.
Conclusions:
- GRIM-19 is essential for successful embryo implantation.
- GRIM-19 regulates endometrial receptivity by modulating cell adhesion, apoptosis, and immune tolerance.
- GRIM-19 influences implantation through pathways involving STAT3, IL-11, and TNF-α.
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