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

Hume, Laura; Edge, Jessica C.; Tinning, Haidee; Wang, Dapeng; Taylor, Alysha S.; Ovchinnikov, Vladimir; Geijer-Simpson, Annika; Vrljicak, Pavle; Brosens, Jan J.; Lucas, Emma S.; Simson, Nigel A.B.; Shillito, Jane; Forbes, Karen; O’Connell, Mary J.; Forde, Niamh

doi:10.1016/j.isci.2023.106339

Cited by 7 publications

(1 citation statement)

References 61 publications

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“…Samples were then centrifuged for 15 min at 14,000 g at 4°C and supernatant transferred to Eppendorf’s alongside a sample of lysis buffer for proteomics analysis. Tandem Mass Tag Labelling and High pH reversed-phase chromatography as carried out as previously described (51) by the University of Bristol core facility with minor modifications. These were the raw data files were processed and quantified using Proteome Discoverer software v2.1 (Thermo Scientific) and searched against the UniProt Bos taurus database (downloaded October 2021: 37512 entries) using the SEQUEST HT algorithm.…”

Section: Methodsmentioning

confidence: 99%

Biosensor capability of the endometrium is mediated in part, by altered miRNA cargo from conceptus-derived extracellular vesicles

De Bem,

Bridi,

Tinning

et al. 2023

Preprint

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We tested the hypothesis that the biosensor capability of the endometrium is mediated in part, by the effect of different cargo contained in the extracellular vesicles secreted by the conceptus during the peri-implantation period of pregnancy. We transferredBos taurus taurusembryos of different origin:In vivo(high developmental potential (IV)),in vitro(intermediate developmental potential (IVF)), or cloned (low developmental potential (NT)), intoBos taurus indicusrecipients. Extracellular vesicles (EVs) recovered from Day 16 conceptus conditioned medium were characterized and their microRNA (miRNA) cargo sequenced alongside RNA sequencing of their respective endometria. There were substantial differences in the endometrial response toin vivoVsin vitroandin vivoVs cloned conceptuses (1153 and 334DEGs respectively) with limited differences betweenin vitroVs cloned conceptuses (36 DEGs). miRNA cargo was similar between all three groups (426 common cargo) differences betweenin vivoand cloned (8 miRNAs), andin vivoandin vitro(6 miRNAs) observed. Treatment of endometrial epithelial cells with mimic or inhibitors for miR-128 and miR-1298 changes to the proteomic content of target cells (96, and 85 respectively) of which mRNAs are altered in the endometriumin vivo(PLXDC2, COPG1, HSPA12A, MCM5, TBL1XR1, and TTF). In conclusion, we have determined that the biosensor capability of the endometrium is mediated in part, by its response to different EVs miRNA cargo produced by the conceptus during the peri-implantation period of pregnancy.SIGNIFICANCE STATEMENTDuring the peri-implantation period of pregnancy in mammals, the endometrium acts as a biosensor for the developmental competency of the embryo. However, the mechanism by which biosensor capability of the endometrium is established, remains elusive. In this study, we show that embryos of different developmental competencies have distinct microRNA cargo contained in their extracellular vesicles (EVs). Exposure of the endometrium to these conceptuses alters the transcriptional response of the endometrium during the process of pregnancy recognition. This differential response is mediated in part, by the delivery and action of the these differentially abundant microRNAs into EVs. Here we propose differences in EV-mediated miRNA cargo are responsible in part for this biosensor capability of the endometrium.

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Section: Methodsmentioning

confidence: 99%