miR-145 suppresses embryo–epithelial juxtacrine communication at implantation by modulating maternal IGF1R

Abstract

Successful implantation requires the synchronization of viable embryonic development with endometrial receptivity. The mechanisms allowing for the initiation of crosstalk between the embryo and the endometrium remain elusive; however, recent studies have revealed that there are alterations in endometrial microRNAs (miRs) in women suffering repeated implantation failure and that one of the altered miRs is miR-145. We assessed the role of miR-145 and its target IGF1R, in early implantation. miR-145 overexpression and IGF1R knockdown were achieved in Ishikawa endometrial cells. Quantitative PCR, western blotting and 39UTR luciferase reporter assays confirmed that IGF1R is a direct target of miR-145 in the endometrium. Attachment of mouse embryos or IGF1-coated beads to endometrial epithelial cells was used to study the effects of altered miR-145 and/or IGF1R expression on early implantation events. miR-145 overexpression or specific reduction of IGF1R impaired attachment in both cases. An IGF1R target protector prevented the miR-145-mediated reduction in IGF1R and reversed the effect of miR-145 overexpression on attachment. The data demonstrate that miR-145 influences embryo attachment by reducing the level of IGF1R in endometrium.

MicroRNA and Embryo Implantation

“…MicroRNA‐145 is also elevated in the RIF endometria . Over‐expression of miR‐145 blocks interaction of embryonic IGF‐I (insulin‐like growth factor 1) with maternal IGF‐I receptor during implantation . The endometrial expression of miR‐451, miR‐424, miR‐125b, and miR‐30b is down‐regulated in women with high progesterone at the time of hCG injection when compared to those with normal progesterone in assisted reproduction treatment …”

Difference of Cyclooxygenase-2 (COX2) Expression in Endometrium Between Patients with Polycystic Ovary Syndrome (PCOS) and Fertile Women

“…Endometrial receptivity is physiologically characterized by pinopods, special protrusions on the membrane surface of the endometrial epithelium, as a sign of endometrial receptivity morphologically (Kang et al, 2015). Pinopod expression is limited to a short period, a maximum of 2 days in the menstrual cycle, in "the window of implantation".…”

“…Receptive uterine environment is an important requirement for embryo implantation. The endometrium should be conducive to allow attachment, implantation and early placental growth for the continuation of early pregnancy (Kang et al, 2015).…”

Non-invasive intra-uterine administration of Botulinum Toxin A enhances endometrial angiogenesis and improves the rates of embryo implantation

“…Human Umbilical Vein Cells (HUVEC, ATCC) and Human Uterine Microvascular Endothelial Cells (HUtMEC, PromoCell) were maintained in EGM TM -2 endometrial cell growth medium 2 (Lonza) and Endothelial Cell Growth Medium MV (PromoCell) respectively. Ishikawa (ATCC) and CRL-4003 cells (kindly gifted from the laboratory of Dr. Haeng Seok Song) were maintained in DMEM/F12 media (Gibco, Grand Island, NY, USA) supplemented with 10% fetal bovine serum (Gibco, Grand Island, NY, USA) and 1% penicillin-streptomycin (Gibco, Grand Island, NY, USA) as previously described [28]. All experiments were conducted using cells of the passages between 1 and 10.…”