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 transferred Bos taurus taurus embryos of different origin, in vivo (high developmental potential (IV)), in vitro (intermediate developmental potential (IVF)), or cloned (low developmental potential (NT)), into Bos taurus indicus recipients. 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 to in vivo versus in vitro and in vivo versus cloned conceptuses (1153 and 334DEGs respectively) with limited differences between in vitro Vs cloned conceptuses (36 DEGs). The miRNA cargo contained in conceptus-derived EVs was similar between all three groups (426 miRNA in common). Only 8 miRNAs were different between in vivo and cloned conceptuses, while only 6 miRNAs were different between in vivo and in vitro-derived conceptuses. Treatment of endometrial epithelial cells with mimic or inhibitors for miR-128 and miR-1298 changed the proteomic content of target cells (96 and 85, respectively) of which mRNAs are altered in the endometrium in 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. Differences in the response of the endometrium to embryos with different developmental competencies have been reported. Here we transfer embryos with different developmental potential (in vivo - high likelihood of pregnancy success; in vitro - intermediate-quality embryos; and clones - low developmental competency) into synchronized recipients and investigate the microRNA cargo contents of extracellular vesicles (EVs) produced by the conceptus during the peri-implantation period of pregnancy (Day 16). Differences in miRNA cargo are shown, and over-represented pathways that are modified in the endometrium when exposed to these conceptuses with different developmental competencies are shown. We propose that different microRNA cargo packaged in the conceptus mediate, in part, the biosensor response of the endometrium in vivo.image