Mouse double minute homologue 2 (MDM2) downregulation by miR-661 impairs human endometrial epithelial cell adhesive capacity
Amy Winship, Amanda Ton, Michelle Van Sinderen, Ellen Menkhorst, Katarzyna Rainczuk, Meaghan Griffiths, Carly Cuman, Evdokia Dimitriadis
REPRODUCTION FERTILITY AND DEVELOPMENT | CSIRO PUBLISHING | Published : 2018
Human blastocysts that fail to implant following IVF secrete elevated levels of miR-661, which is taken up by primary human endometrial epithelial cells (HEECs) and impairs their adhesive capability. MicroRNA miR-661 downregulates mouse double minute homologue 2 (MDM2) and MDM4 in other epithelial cell types to activate p53; however, this has not been examined in the endometrium. In this study MDM2 protein was detected in the luminal epithelium of the endometrium, the site of blastocyst attachment, during the mid secretory receptive phase of the menstrual cycle. The effects of miR-661 on gene expression in and adhesion of endometrial cells was also examined. MiR-661 overexpression consistent..View full abstract
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Awarded by NHMRC Australia Project Grant
Awarded by NHMRC Australia Senior Research Fellowship
The authors would like to thank Sister Judi Hocking for her assistance and acknowledge all the women that donated endometrial tissue. We acknowledge the Monash IVF embryology team for collecting blastocyst spent media samples. This work was supported by NHMRC Australia Project Grant (1098321) and the Victorian Government's Operational Infrastructure Support Program. Evdokia Dimitriadis was supported by a NHMRC Australia Senior Research Fellowship (550905). Amy Winship was supported by a Cancer Council Victoria Postdoctoral Fellowship. Amanda Ton was supported by a Monash University Jubilee Honours Scholarship.