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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
Genes involved in implantation
L A Salamonsen1, G Nie, E Dimitriadis
1Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia. lois.salamonsen@med.monash.edu.au
Abstract:
The endometrium is normally a hostile environment for an embryo, except for a short phase in each reproductive cycle known as the 'window of receptivity'. The precise molecular events involved in this transformation are not well understood. Application of state-of-the-art techniques of the 1990s has identified some of the genes involved, which are reviewed here. Mice with a null mutation in either the gene for leukemia inhibitory factor or the interleukin-11 receptor alpha chain are infertile, owing in both cases to a failure of embryo implantation. Both of these genes are expressed in the human endometrium with patterns suggesting a role in human fertility. The technique of RNA differential display has been applied to a comparison of the expression of genes at implantation sites v. inter-implantation sites in the mouse uterus on the first day of implantation, and has defined additional genes whose products may be important for this process. Among these are the calcium-binding protein D9K, the monoclonal non-specific suppressor factor beta, and the splicing factor SC35. The major challenge is to determine whether manipulation of such genes can increase or decrease endometrial receptivity in humans.
Insights
Understanding endometrial receptivity is key for fertility. Leukemia inhibitory factor and interleukin-11 receptor alpha chain are crucial for embryo implantation, with potential roles in human fertility.
Area of Science:
- Reproductive biology
- Molecular genetics
- Endocrinology
Background:
- The endometrium presents a hostile environment for embryos, except during a brief fertile window.
- The molecular mechanisms regulating endometrial receptivity remain largely unknown.
- Previous research identified key genes like leukemia inhibitory factor (LIF) and interleukin-11 receptor alpha chain (IL-11Rα).
Purpose of the Study:
- To review current knowledge on genes influencing endometrial receptivity.
- To investigate the role of LIF and IL-11Rα in embryo implantation.
- To identify novel genes involved in the implantation process.
Main Methods:
- Review of literature on endometrial receptivity genes.
- Analysis of mouse models with null mutations in LIF and IL-11Rα genes.
- Application of RNA differential display to compare gene expression in mouse uterine implantation and inter-implantation sites.
Main Results:
- Mice lacking LIF or IL-11Rα exhibit infertility due to implantation failure.
- LIF and IL-11Rα show expression patterns in human endometrium suggesting a role in fertility.
- RNA differential display identified calcium-binding protein D9K, non-specific suppressor factor beta, and splicing factor SC35 as potentially important genes.
Conclusions:
- LIF and IL-11Rα are critical for successful embryo implantation.
- These genes may play a significant role in human reproductive processes.
- Further research is needed to explore the therapeutic potential of manipulating these genes for endometrial receptivity.
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