An evolutionarily conserved microRNA, miR-185, regulates key pathways that may contribute to implantation failure.

Smith, W.; Edge, J. C.; Tinning, H.; Butt, Z.; Deligianni, F.; Morales, C.; Muter, J.; Brosens, J.; Mascarenhas, M.; Bhandari, H.; O'Connell, M. J.; Lucas, E.; Simpson, N.; Forde, N.

doi:10.1101/2025.01.15.633123

bioRxiv · 10.1101/2025.01.15.633123

An evolutionarily conserved microRNA, miR-185, regulates key pathways that may contribute to implantation failure.

Smith, W.·Edge, J. C.·Tinning, H.·Butt, Z.·Deligianni, F.·Morales, C.·Muter, J.·Brosens, J.·Mascarenhas, M.·Bhandari, H.·O'Connell, M. J.·Lucas, E.·Simpson, N.·Forde, N.

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Abstract

Recurrent implantation failure (RIF) is defined after three or more good quality embryo transfers following in vitro fertilisation without a successful pregnancy outcome. Many factors contribute to RIF however, the endometrial contribution remains unclear. Previous work by our group has identified a micro-RNA (miRNA) miR-185-5p as conserved across placental mammal irrespective of implantation strategies. We tested the hypothesis that miR-185-5p and the pathways it regulates, may be disrupted in the endometria of women with RIF. A human endometrial epithelial cells line (Ishikawa cells) was transfected with mimics or inhibitors for miR-185-5p for 24 (for implantation assay) or 48 hr (for proteomic analysis) along with non-targeting controls. There was a significant different in percentage attachment of BeWoW spheroids to cells transfected with miR-185-5p mimic compared to inhibitor (P<0.05). Transfection of epithelial cells with miR-185-5p altered expression of 1450 (mimic alone) and 509 (inhibitor alone) proteins respective of which, 146 were modified by both. Comparison of predicted targets of miR-185-5p, proteins modified by this study, and key endometrial genes from the literature determined genes and proteins associated with CNP family were further investigated in biopsies from individuals with (n=10) and without RIF (n=9) with CSNK1D expression significantly lower (p<0.05) in individuals with RIF. Collectively these data demonstrate that miR-185-5p modifies pathways that are important for successful implantation in humans.

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Smith, W., Edge, J. C., Tinning, H., Butt, Z., Deligianni, F., Morales, C., Muter, J., Brosens, J., Mascarenhas, M., Bhandari, H., O'Connell, M. J., Lucas, E., Simpson, N., Forde, N.. 2025-01-15. An evolutionarily conserved microRNA, miR-185, regulates key pathways that may contribute to implantation failure.. https://doi.org/10.1101/2025.01.15.633123

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