Loux Shavahn C, Scoggin Kirsten E, Bruemmer Jason E, Canisso Igor F, Troedsson Mats H T, Squires Edward L, Ball Barry A
Department of Veterinary Science, University of Kentucky, Lexington, KY, United States of America.
Department of Animal Sciences, Colorado State University, Fort Collins, CO, United States of America.
PLoS One. 2017 Apr 7;12(4):e0175045. doi: 10.1371/journal.pone.0175045. eCollection 2017.
MicroRNAs (miRNAs) are small, non-coding RNAs which are produced throughout the body. Individual tissues tend to have a specific expression profile and excrete many of these miRNAs into circulation. These circulating miRNAs may be diagnostically valuable biomarkers for assessing the presence of disease while minimizing invasive testing. In women, numerous circulating miRNAs have been identified which change significantly during pregnancy-related complications (e.g. chorioamnionitis, eclampsia, recurrent pregnancy loss); however, no prior work has been done in this area in the horse. To identify pregnancy-specific miRNAs, we collected serial whole blood samples in pregnant mares at 8, 9, 10 m of gestation and post-partum, as well as from non-pregnant (diestrous) mares. In total, we evaluated a panel of 178 miRNAs using qPCR, eventually identifying five miRNAs of interest. One miRNA (miR-374b) was differentially regulated through late gestation and four miRNAs (miR-454, miR-133b, miR-486-5p and miR-204b) were differentially regulated between the pregnant and non-pregnant samples. We were able to identify putative targets for the differentially regulated miRNAs using two separate target prediction programs, miRDB and Ingenuity Pathway Analysis. The targets for the miRNAs differentially regulated during pregnancy were predicted to be involved in signaling pathways such as the STAT3 pathway and PI3/AKT signaling pathway, as well as more endocrine-based pathways, including the GnRH, prolactin and insulin signaling pathways. In summary, this study provides novel information about the changes occurring in circulating miRNAs during normal pregnancy, as well as attempting to predict the biological effects induced by these miRNAs.
微小RNA（miRNA）是在全身产生的小型非编码RNA。各个组织往往具有特定的表达谱，并将许多此类miRNA排泄到循环系统中。这些循环miRNA可能是用于评估疾病存在的具有诊断价值的生物标志物，同时可尽量减少侵入性检测。在女性中，已鉴定出许多循环miRNA在妊娠相关并发症（如绒毛膜羊膜炎、子痫、复发性流产）期间会发生显著变化；然而，此前在马的这一领域尚未开展任何研究。为了鉴定妊娠特异性miRNA，我们在妊娠8、9、10个月以及产后的怀孕母马中采集了系列全血样本，同时也采集了未怀孕（处于间情期）母马的样本。我们总共使用qPCR评估了178种miRNA，最终鉴定出5种感兴趣的miRNA。一种miRNA（miR-374b）在妊娠后期受到差异调节，另外四种miRNA（miR-454、miR-133b、miR-486-5p和miR-204b）在怀孕和未怀孕样本之间受到差异调节。我们能够使用两个独立的靶标预测程序miRDB和 Ingenuity Pathway Analysis来鉴定差异调节的miRNA的推定靶标。在妊娠期间差异调节的miRNA的靶标预计参与信号通路，如STAT3通路和PI3/AKT信号通路，以及更多基于内分泌的通路，包括GnRH、催乳素和胰岛素信号通路。总之，本研究提供了关于正常妊娠期间循环miRNA发生变化的新信息，并试图预测这些miRNA诱导的生物学效应。
