MicroRNAs emerging coordinate with placental mammals alter pathways in endometrial epithelia important for endometrial function
Laura Hume,
Jessica C. Edge,
Haidee Tinning,
Dapeng T. Wang,
Alysha S. Taylor,
Vladimir Ovchinnikov,
Annika V. Geijer-Simpson,
Pavle Vrljicak,
Jan J. Brosens,
Emma S. Lucas,
Nigel A.B. Simpson,
Jayne Shillito,
Karen Forbes,
Mary J. O’Connell,
Niamh Forde
Affiliations
Laura Hume
Discovery and Translational Sciences Department, Leeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, LS2 9JT, UK
Jessica C. Edge
Discovery and Translational Sciences Department, Leeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, LS2 9JT, UK
Haidee Tinning
Discovery and Translational Sciences Department, Leeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, LS2 9JT, UK
Dapeng T. Wang
LeedsOmics, University of Leeds, Leeds, UK
Alysha S. Taylor
Discovery and Translational Sciences Department, Leeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, LS2 9JT, UK; School of Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK
Vladimir Ovchinnikov
School of Life Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, NG7 2RD, UK
Annika V. Geijer-Simpson
Discovery and Translational Sciences Department, Leeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, LS2 9JT, UK; School of Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK
Pavle Vrljicak
Division of Biomedical Sciences, Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, Coventry CV2 2DX, UK
Jan J. Brosens
Division of Biomedical Sciences, Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, Coventry CV2 2DX, UK; Tommy’s National Centre for Miscarriage Research, University Hospital Coventry and Warwickshire, Coventry CV2 2DX, UK
Emma S. Lucas
Division of Biomedical Sciences, Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, Coventry CV2 2DX, UK
Nigel A.B. Simpson
Department of Women’s and Children’s Health, School of Medicine, University of Leeds, Leeds LS2 9JT, UK; Leeds Teaching Hospitals Trust, Beckett St, Leeds LS9 7TF, UK
Jayne Shillito
Leeds Teaching Hospitals Trust, Beckett St, Leeds LS9 7TF, UK
Karen Forbes
Discovery and Translational Sciences Department, Leeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, LS2 9JT, UK
Mary J. O’Connell
School of Life Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, NG7 2RD, UK
Niamh Forde
Discovery and Translational Sciences Department, Leeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, LS2 9JT, UK; Corresponding author
Summary: 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.
