Hum. Reprod. Advance Access published online on April 11, 2008
Human Reproduction, doi:10.1093/humrep/den082
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Myeloid ecotropic viral integration site 1 (MEIS) 1 involvement in embryonic implantation
1 Reproductive Medicine Center, Tongji Hospital, Tongji Medicine College, Huazhong, University of Science and Technology, 1095 JieFang Avenue, Wuhan 430030, People’s Republic of China 2 Department of Human Genetics, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
3 Correspondence address. E-mail: zhu_guijin{at}sina.com
BACKGROUND: The HOXA10 homeobox gene controls embryonic uterine development and adult endometrial receptivity. The three-amino-acid loop extension (TALE) family homeobox genes like myeloid ecotropic viral integration site 1 (MEIS) provide enhanced target gene activation and specificity in HOX-regulated cellular processes by acting as HOX cofactors.
METHODS AND RESULTS: Analysis of an Affymetrix data set in the public domain showed high expression of MEIS1 in human endometrium. MEIS1 expression was confirmed during the human menstrual cycle by RT–PCR and in situ hybridization and was increased during the secretory compared with proliferative phase of the cycle (P = 0.0001), the time of implantation. To assess the importance of maternal Meis1 expression in a mouse model, the uteri of Day 2 pregnant mice were injected with Meis1 over-expression or small interfering RNA (siRNA) constructs. Blocking Meis1 expression by siRNA before implantation significantly reduced average implantation rates (P = 0.00001). Increased or decreased Meis1 expression significantly increased or decreased the expression of integrin β3, a transcriptional target of HOXA10 and an important factor in early embryo-endometrium interactions (P = 0.006). Manipulating Meis1 expression before implantation also dramatically affected the number of pinopodes, uterine endometrial epithelial projections that develop at the time of endometrial receptivity.
CONCLUSIONS: The results suggest that in mouse, meis1 contributes to regulating endometrial development during the menstrual cycle and establishing the conditions necessary for implantation.
Key words: embryonic implantation/endometrium/HOXA10/integrin β3/MEIS1
These authors contributed equally to this study. Submitted on October 6, 2007; resubmitted on February 5, 2008; accepted on February 22, 2008.
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