Abstract
BackgroundThe most common indication for cesarean section (CS) in nulliparous women is dystocia secondary to ineffective myometrial contractility. The aim of this study was to identify a molecular profile in myometrium associated with dystocic labor.MethodsMyometrial biopsies were obtained from the upper incisional margins of nulliparous women undergoing lower segment CS for dystocia (n = 4) and control women undergoing CS in the second stage who had demonstrated efficient uterine action during the first stage of labor (n = 4). All patients were in spontaneous (non-induced) labor and had received intrapartum oxytocin to accelerate labor. RNA was extracted from biopsies and hybridized to Affymetrix HuGene U133A Plus 2 microarrays. Internal validation was performed using quantitative SYBR Green Real-Time PCR.ResultsSeventy genes were differentially expressed between the two groups. 58 genes were down-regulated in the dystocia group. Gene ontology analysis revealed 12 of the 58 down-regulated genes were involved in the immune response. These included (ERAP2, (8.67 fold change (FC)) HLA-DQB1 (7.88 FC) CD28 (2.60 FC), LILRA3 (2.87 FC) and TGFBR3 (2.1 FC)) Hierarchical clustering demonstrated a difference in global gene expression patterns between the samples from dystocic and non-dystocic labours. RT-PCR validation was performed on 4 genes ERAP2, CD28, LILRA3 and TGFBR3ConclusionThese findings suggest an underlying molecular basis for dystocia in nulliparous women in spontaneous labor. Differentially expressed genes suggest an important role for the immune response in dystocic labor and may provide important indicators for new diagnostic assays and potential intrapartum therapeutic targets.
Highlights
The most common indication for cesarean section (CS) in nulliparous women is dystocia secondary to ineffective myometrial contractility
CS rates vary between institutions, term singleton cephalic nulliparas (TSCN) CS rates correlate with institutional CS rates and we have previously documented that 98% of
Our study demonstrates an obvious difference in the myometrial transcriptomic profiles in women with dystocia and efficient uterine action but it raises a number of questions
Summary
The most common indication for cesarean section (CS) in nulliparous women is dystocia secondary to ineffective myometrial contractility. As cesarean section (CS) rates continue to rise throughout the developed world, an improved understanding of the molecular mechanisms underlying parturition at term is urgently required. In 1020% of cases of dystocia, myometrial response to oxytocin is poor and CS becomes the only safe option following prolonged labor [8]. It is believed this complication is likely to increase mainly due to delayed childbearing and increased prevalence of obesity in the obstetric population both factors which adversely affect intrapartum myometrial contractility [9,10]. An improved understanding of the molecular mechanisms underlying dystocic labor and may result in alternative adjuvants to oxytocin
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