Abstract
BackgroundPreterm birth is the primary cause of the neonatal mortality and morbidity. There will be no preterm birth without a cervical softening. Nitric oxide (NO) is shown to be a mediator of term cervical ripening. The aim of this study was to investigate mRNA expression of the three isomers of NO synthases (NOS) and to identify them by immunohistochemistry in the human cervix at preterm birth compared to term.MethodsThe three isomers of NOS- inducible (iNOS), endothelial (eNOS) and neuronal (bNOS) – were investigated in the human cervix. The expression of mRNA was determined using Real-Time Multiplex RT-PCR. The localisation of synthases in the cervical tissue was analysed using immunohistochemistry. Cervical biopsies were obtained from 4 groups of women without clinical signs of infection: preterm (PTL), term labour (TL), preterm not in labour (PTnotL) and term not in labour (TnotL) patients. One-Way ANOVA, Kruskal-Wallis, Student t-test or Mann-Whitney test were applied as appropriate to determine statistically significant differences among the groups.ResultsPatients in preterm labour had significantly (p < 0.01) higher mRNA levels of all the three NOS isomers compared to those in term labour. Women not in labour, irrespective of gestational age, thus with unripe cervices, had significantly lower eNOS mRNA levels compared to those in labour (p < 0.01). Immunoreactivity for all three NO synthases was observed in each examined sample in all groups. The bNOS staining was the most prominent.ConclusionThe mRNA levels were higher in the preterm labour group compared to the women at term labour. The significant increase of the eNOS mRNA expression, from the unripe to the favourable cervical state during labour, may indicate a role of eNOS and supports the role of NO in the cervical ripening process. All the three synthases were identified by immunohistochemistry in all the groups of study.
Highlights
IntroductionThere will be no preterm birth without a cervical softening
Preterm birth is the primary cause of the neonatal mortality and morbidity
The endogenous peroxidase activity was eliminated by pre-treatment with 0.3% hydrogen peroxide in methanol for 30 minutes followed by washing in phosphate-buffered saline (PBS)/BSA (0,05%)
Summary
There will be no preterm birth without a cervical softening. Nitric oxide (NO) is shown to be a mediator of term cervical ripening. The frequency of premature birth has not changed significantly during the past two decades and the basic mechanisms underlying the initiation of both preterm and term cervical ripening and labour remain unknown [1]. The cervical remodelling detected clinically, consists of softening, effacement and dilation. This corresponds to vast changes in the extracellular matrix (ECM) composition and tissue remodelling by proteolytic enzymes [3,4]. The cervical ripening procedure is to be considered an inflammatory reaction. The 100-fold increase of interleukines is likely to be responsible for the recruitment of leukocytes/influx of white blood cells triggering the inflammatory process [1,5,6]
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