Department of Metabolism, Digestion & Reproduction, Faculty of Medicine, Imperial College London, London, United Kingdom.
College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
PLoS One. 2021 Nov 19;16(11):e0260119. doi: 10.1371/journal.pone.0260119. eCollection 2021.
High throughput sequencing has previously identified differentially expressed genes (DEGs) and enriched signalling networks in human myometrium for term (≥37 weeks) gestation labour, when defined as a singular state of activity at comparison to the non-labouring state. However, transcriptome changes that occur during transition from early to established labour (defined as ≤3 and >3 cm cervical dilatation, respectively) and potentially altered by fetal membrane rupture (ROM), when adapting from onset to completion of childbirth, remained to be defined. In the present study, we assessed whether differences for these two clinically observable factors of labour are associated with different myometrial transcriptome profiles. Analysis of our tissue ('bulk') RNA-seq data (NCBI Gene Expression Omnibus: GSE80172) with classification of labour into four groups, each compared to the same non-labour group, identified more DEGs for early than established labour; ROM was the strongest up-regulator of DEGs. We propose that lower DEGs frequency for early labour and/or ROM negative myometrium was attributed to bulk RNA-seq limitations associated with tissue heterogeneity, as well as the possibility that processes other than gene transcription are of more importance at labour onset. Integrative analysis with future data from additional samples, which have at least equivalent refined clinical classification for labour status, and alternative omics approaches will help to explain what truly contributes to transcriptomic changes that are critical for labour onset. Lastly, we identified five DEGs common to all labour groupings; two of which (AREG and PER3) were validated by qPCR and not differentially expressed in placenta and choriodecidua.
高通量测序先前已经鉴定了足月(≥37 周)妊娠分娩时人子宫肌层中的差异表达基因(DEGs)和富集信号通路,此时将其定义为与非分娩状态相比的单一活动状态。然而,在从早期到已建立的分娩(分别定义为≤3 和>3cm 宫颈扩张)的过渡期间发生的转录组变化以及可能因胎膜破裂(ROM)而改变,当从开始到完成分娩时适应时,仍然需要定义。在本研究中,我们评估了这些两个临床上可观察的分娩因素的差异是否与不同的子宫肌层转录组图谱相关。对我们的组织(“批量”)RNA-seq 数据(NCBI Gene Expression Omnibus:GSE80172)进行分析,并将分娩分类为四个组,每个组与相同的非分娩组进行比较,发现早期分娩比已建立的分娩有更多的 DEGs;ROM 是 DEGs 上调最强的因素。我们提出,早期分娩和/或 ROM 阴性子宫肌层的 DEGs 频率较低归因于批量 RNA-seq 与组织异质性相关的局限性,以及在分娩开始时转录以外的其他过程可能更为重要的可能性。与具有至少等同的精细劳动状态临床分类的其他样本的未来数据进行综合分析,以及替代组学方法将有助于解释真正有助于对分娩开始至关重要的转录组变化的因素。最后,我们确定了所有劳动分组中都存在的五个 DEGs;其中两个(AREG 和 PER3)通过 qPCR 进行了验证,在胎盘和绒毛膜蜕膜中没有差异表达。