MicroRNA-199a mediates mucin 1 expression in mouse uterus during implantation
Wilasinee Inyawilert A , Tzu-Yen Fu A , Chun-Ting Lin A B and Pin-Chi Tang A C D EA Department of Animal Science, National Chung Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan.
B BioLASCO Taiwan Co., Ltd, 3F., 316 Chung Yang Road, Taipei 115, Taiwan.
C Agricultural Biotechnology Center, National Chung Hsing University, Taichung 40227, Taiwan.
D Center for the Integrative and Evolutionary Galliformes Genomics, iEGG Center, National Chung Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan.
E Corresponding author. Email: pctang@dragon.nchu.edu.tw
Reproduction, Fertility and Development 26(5) 653-664 https://doi.org/10.1071/RD12097
Submitted: 29 March 2012 Accepted: 16 April 2013 Published: 13 June 2013
Abstract
Embryo implantation is a complicated process involving interactions between the blastocyst and the luminal epithelium of the receptive uterus. Mucin 1 (MUC1) is an integral membrane glycoprotein expressed apically by secretory epithelial cells and the glandular epithelium in different organs, including the uterus. It is believed that loss of MUC1 on the surface of uterine epithelial cells is necessary for embryo implantation. The endogenous non-protein coding microRNAs (miRNAs) of 21–24 nucleotides are found in diverse organisms. It has been shown that miRNAs participate in a range of cellular processes by regulating gene expression at the post-transcriptional level. In the present study, the regulatory role of miRNA-199a on the expression of MUC1 in mouse uterus during implantation was investigated for its effect on embryo implantation. Western blotting and immunohistochemistry results showed high MUC1 expression on Day 0.5 and low expression by Day 4.5 of pregnancy. In contrast with MUC1 expression, increased miRNA-199a expression was evident at Day 4.5 of pregnancy, as measured by real-time reverse transcription–polymerase chain reaction. In addition, we demonstrated direct binding of miRNA-199a to the 3′-untranslated region of MUC1. Transfection of miRNA-199a into mouse uterine epithelial cells isolated from Day 0.5 of pregnancy also downregulated expression of MUC1. Therefore, the present study provides evidence that MUC1 is a direct target of miRNA-199a and suggests that development of novel strategies to facilitate a successful pregnancy and repair implantation failure humans may include miRNA.
Additional keywords: anti-adhesion, endometrial epithelial cells, gene regulation, implantation window, miRNAs, posttranscriptional regulation, receptive phase, reciprocal interaction.
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