Preterm birth is recognized as the primary cause of infant mortality worldwide. Twin pregnancies are significantly more at risk of preterm birth than singleton pregnancies. A greater understanding of why this is and better modes of treatment and prevention are needed. Key to this is determining the differing pathophysiological mechanisms of preterm birth in twins, including the role of the myometrium and premature uterine contraction. We performed RNA sequencing (RNA-Seq) of human myometrium from singleton and twin pregnancies at term (> 37+0 weeks) and preterm (< 37+0 weeks), collected during pre-labour Caesarean Section. RNA-Seq libraries were prepared from polyA-selected RNA and sequenced on the Illumina HiSeq 4000 platform. Differentially expressed genes (DEGs), GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment were conducted using R software. Significance was determined with a false discovery rate-adjusted P value of <0.05. Only 3 DEGs were identified between gestational age-matched singleton and twin myometrium and only 1 DEG identified between singleton term and twin preterm tissues. Comparison of singleton preterm myometrium with twin term myometrium however, revealed 75 down-regulated and 24 up-regulated genes in twin myometrium. This included genes associated with inflammation and immune response, T cell maturation and differentiation and steroid biosynthesis. GO and KEGG enrichment analyses for biologically relevant processes and functions also revealed several terms related to inflammation and immune response, as well as cytokine-cytokine receptor interaction and chemokine receptor signalling. Data indicate that little or no differences exist in the transcriptome of singleton and twin myometrium when matched for gestational age. The significant up- and down-regulation of genes identified between preterm singleton and twin myometrium at term may point to transcriptome changes associated with the chronic levels of uterine stretch in twin pregnancy or genes associated with the myometrium transitioning to labour onset.

中文翻译：

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RNA-Seq比较单胎和双胎妊娠的子宫肌层转录组。

早产被认为是全世界婴儿死亡的主要原因。双胎妊娠比单胎妊娠的早产风险要高得多。为什么要这样，需要有更多的了解，并且需要更好的治疗和预防方式。关键在于确定双胞胎早产的不同病理生理机制，包括子宫肌层和子宫过早收缩的作用。我们在分娩前剖腹产期间足月（> 37 + 0周）和早产（<37 + 0周）对单胎和双胎妊娠的人子宫肌层进行了RNA测序（RNA-Seq）。从polyA选择的RNA制备RNA-Seq文库，并在Illumina HiSeq 4000平台上测序。差异表达基因（DEG），使用R软件进行了GO（基因本体论）和KEGG（京都基因与基因组百科全书）途径富集。通过错误发现率调整后的P值<0.05确定了显着性。在胎龄匹配的单胎和双胎子宫肌层之间仅鉴定出3个DEG，在单胎足月和双胎早产组织之间仅鉴定出1个DEG。比较单胎早产儿的子宫肌层和双生子的子宫肌层，发现在双胞胎的子宫肌层中有75个下调基因和24个上调基因。其中包括与炎症和免疫反应，T细胞成熟和分化以及类固醇生物合成相关的基因。GO和KEGG对生物学相关过程和功能的富集分析还揭示了与炎症和免疫反应有关的几个术语，以及细胞因子-细胞因子受体相互作用和趋化因子受体信号传导。数据表明，与胎龄匹配时，单胎和双胎子宫肌层的转录组几乎没有差异。足月早产单胎和双胎子宫肌层之间鉴定的基因的显着上调和下调可能表明与双胎妊娠中子宫舒张的慢性水平有关的转录组变化或与子宫肌层转变为分娩发作有关的基因。