Let-7-mediated suppression of mucin 1 expression in the mouse uterus during embryo implantation

Abstract

Mucin 1 (Muc1) is an integral transmembrane mucin glycoprotein expressed on the apical surface of most epithelia. It is considered to be a barrier to the regulation of embryo implantation by inhibiting attachment of the embryo to the endometrium. Therefore, loss of Muc1 on the surface of uterine epithelial cells is necessary for embryo implantation. Studies have demonstrated that microRNAs (miRNAs) play a key role in enhancing embryo implantation in mammals. In this study, we investigated the regulatory role of two miRNAs (let-7a and let-7b) on the expression of Muc1 in mouse uteri during implantation. Western blotting indicated that Muc1 expression was highest on day1 of pregnancy and constantly decreased thereafter until day 4. In contrast to Muc1 expression, increased expression of let-7a and let-7b was evident on day 4 of pregnancy as measured by real-time reverse transcription-polymerase chain reaction (real-time RT-PCR). We demonstrated direct binding of let-7a and let-7b to the 3’untranslated region of muc1. Furthermore, Muc1 expression was suppressed after transfection of mouse uterine epithelial cells isolated from day 1 of pregnancy with let-7a and let-7b. In summary, the present study provides evidence that Muc1 is a direct target of let-7a and let-7b. Additionally, the current study suggests that miRNAs are novel targets which can be used to facilitate a successful pregnancy and repair implantation failure.

Calcitonin administration improves endometrial receptivity via regulation of LIF, Muc‐1 and microRNA Let‐7a in mice

“…Previous studies have demonstrated that direct interaction of Let-7a with the 3′-untranslated region (3′-UTR) of Muc-1 is possible. Moreover, Let-7a can mediate Muc-1 expression (Inyawilert, Fu, Lin, & Tang, 2015).…”

Faecal microRNAs: indicators of imbalance at the host-microbe interface?

“…Mmu-let-7b-3p has also been shown to mediate the epithelial innate immune response via TLR signalling (Hu et al, 2009). Furthermore, let-7b is also known to target Tlr4 and regulates the activation of NF-κB and the expression of downstream genes related to immune responses in Helicobacter pylori infection (Teng et al, 2013) while also binding to the Muc1 gene in epithelial cells (Inyawilert et al, 2015). miR-141-3p is expressed in immune cells (natural killer cells, leukocytes) and both inflamed and noninflamed epithelial cells in the small and large intestine (Lee et al, 2015).…”

MicroRNA and Embryo Implantation

“…The high levels of let‐7 in the receptive uterus could be important for differentiation of a receptive endometrium. One of the targets of let‐7a and let‐7b is Muc1 , which encodes mucin that blocks embryo attachment in many species . In mice, the expression of MUC1 is abundant in the non‐receptive uteri but is greatly reduced in the luminal epithelium in the WOI .…”