MicroRNAs emerging coordinate with placental mammals alter pathways in endometrial epithelia important for endometrial function

• DOI: 10.1016/j.isci.2023.106339
• Publication Date: 2023-03-04T07:06:11Z
• Authors: Laura Hume; Jessica C. Edge; Haidee Tinning; Dapeng Wang; Alysha S. Taylor; Vladimir Ovchinnikov; Annika V. Geijer-...; Pavle Vrljicak; Jan J. Brosens; Emma S. Lucas; Nigel A.B. Simpson; Jayne Shillito; Karen Forbes; Mary J. O’Connell; Niamh Forde
• Keywords: Biological sciences; Embryology; Molecular biology; Science; Developmental biology; Q; Article

We tested the hypothesis that conserved placental mammal-specific microRNAs and their targets facilitate endometrial receptivity to implantation. Expression of miR-340-5p, -542-3p, and -671-5p was regulated by exposure of endometrial epithelial cells to progesterone (10 μg/ml) for 24 h coordinate with 1,713 of their predicted targets. Proteomic analysis of cells transfected with miRNA mimic/inhibitor (48 h: n = 3) revealed 1,745 proteins altered by miR-340-5p (mimic; 1,369, inhibitor; 376) of which 171 were predicted targets and P4-regulated. MiR-542-3p altered 2,353 (mimic; 1,378, inhibitor; 975) 100 which were mirDB predicted, including 46 P4-regulated. MiR-671-5p altered 1,744 proteins (mimic; 1,252, inhibitor; 492) 95 of which were predicted targets and 46 P4-regulated. All miRNAs were detected in luteal phase endometrial biopsies, irrespective of pregnancy outcomes. miR-340-5p expression increased in biopsies from individuals suffering previous and subsequent miscarriage compared to those with subsequent live birth. Dysfunction of these miRNAs and their targets contribute to endometrial-derived recurrent pregnancy loss.