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.

Quantification of the effect of in utero events on lifetime resilience in dairy cows.

Currently, the dairy industry is facing many challenges that could affect its sustainability, including climate change and public perception of the industry. As a result, interest is increasing in the concept of identifying resilient animals, those with a long productive lifespan, as well as good reproductive performance and milk yield. There is much evidence that events in utero, that is, the developmental origins of health and disease hypothesis, alter the life-course health of offspring and we hypothesized that these could alter resilience in calves, where resilience is identified using lifetime data. The aim of this study was to quantify lifetime resilience scores (LRS) using an existing scoring system, based on longevity with secondary corrections for age at first calving and calving interval, and to quantify the effects of in utero events on the LRS using 2 datasets. The first was a large dataset of cattle on 83 farms in Great Britain born from 2006 to 2015 and the second was a smaller, more granular dataset of cattle born between 2003 and 2015 in the Langhill research herd at Scotland's Rural College. Events during dam's pregnancy included health events (lameness, mastitis, use of an antibiotic or anti-inflammatory medication), the effect of heat stress as measured by temperature-humidity index, and perturbations in milk yield and quality (somatic cell count, percentage fat, percentage protein and fat:protein ratio). Daughters born to dams that experienced higher temperature-humidity indexes while they were in utero during the first and third trimesters of pregnancy had lower LRS. Daughter LRS were also lower where milk yields or median fat percentages in the first trimester were low, and when milk yields were high in the third trimester. Dam LRS was positively associated with LRS of their offspring; however, as parity of the dam increased, LRS of their calves decreased. Similarly, in the Langhill herd, dams of a higher parity produced calves with lower LRS. Additionally, dams that recorded a high maximum locomotion score in the third trimester of pregnancy were negatively associated with lower calf LRS in the Langhill herd. Our results suggest that events that occur during pregnancy have lifelong consequences for the calf's lifetime performance. However, experience of higher temperature-humidity indexes, higher dam LRS, and mothers in higher parities explained a relatively small proportion of variation in offspring LRS, which suggests that other factors play a substantial role in determining calf LRS. Although "big data" can contain a considerable amount of noise, similar findings between the 2 datasets indicate it is likely these findings are real.