Biosensor capability of the endometrium is mediated in part, by altered miRNA cargo from conceptus-derived extracellular vesicles
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. Overall design: Endometrium from day 16 pregnant cattle (bos taurus indicus) underwent RNA sequencing. Extracellular vesicles secreted by day 16 bovine (bos taurus taurus) conceptuses for 6 hours in culture medium underwent small miRNA sequencing. Conceptuses were produced by either in vivo (artificial insemination), in vitro fertilisation (IVF), or nuclear transfer techniques.