The Expression And Regulation Of Prostaglandin H Synthase Type-2 In Preterm Labour Myometrium

Preterm labour refers to the total pregnancy time calculated more than 28 weeks gestation but less than 37 weeks since the first day of the last menstrual period. Preterm labour is a common complication, accounting for 5% to 15% of the entire pregnancy, 70% of neonatal deaths and 75% of neonatal morbidity. Over the years the incidence of preterm labor has not decreased. Currently there is no reliable clinical diagnostic index for premature labor, no mention effective treatment. Researches on preterm birth remain to clarify the mechanism, especially the biochemical changes before the onset of labor, hoping to find a better forecasting and effective method for treatment of preterm labor.During pregnancy, the uterus is in a relatively resting state. As the parturition approaches and launches, inflammatory cytokines such as IL-1βand LPS, activate NFκB signaling pathway and cause the expression of labour-associated factors such as PGHS-2, IL-8, OTR significantly increased, promoting the activation and transformation of the uterus and ultimately leading to birth. Preterm labour have been caused by various factors of premature launch, which activate the uterus and make it change from the rest of the premature to conversion. However, the specific molecular mechanisms of preterm birth was inconclusive.In the process of parturition prostaglandins play a key role. Prostaglandins act on the uterine smooth muscle cells, inducing uterus contractionsand then resulting in onset of labor. Prostaglandin H synthase (PGHS) is a prostaglandin biosynthesis rate-limiting enzyme, which converts arachidonic acid to prostaglandin precursors-PGG2 or PGH2, which are then processed to form various forms of prostaglandins, prostacyclin and thromboxane. There are two PGHS isozymes, PGHS-1 and PGHS-2. PGHS-1 is constitutively expressed in various cells, while PGHS-2 is only induced by stimulary factors such as IL-1βand LPS. The expression of PGHS-2 is controlled by complex regulations, among which NF-κB and MAPK signaling pathways are the most important. In the course of pregnancy, progesterone maintain the resting state of the uterus by inhibiting NFκB activation. As labour approaches and launches, progesterone occurs functional withdrawal. In the mean time a number of inflammatory cytokines such as IL-1βand LPS activate NFκB and MAPK signaling pathways, upregulate the expression of PGHS-2, increase the synthesis of prostaglandin, induces contraction of the uterus, and then result in delivery. Premature labor can be caused by a variety of factors, then how is PGHS-2 expressed and regulated in premature myometrium? What is the role and significance of PGHS-2 in preterm labor?In order to define the expression and significance of PGHS-2 in preterm labour, we selected pregnant woman with preterm labor (PTL) and preterm no labor (PTNL) as a research group, term labor (TL) and term no labor (TNL) as a control group. Biopsies of the lower uterine segment myometrium were collected from both group. The myometrial expression of labour-associate factors PGHS-2, IL-8, OTR were detected using real time quantitative PCR (qRT-PCR) and Western blot, and then statistically analyzed combided with the associated clinical data. We detected the contents of PGE2 in the myometrium of TNL and PTNL by enzyme-linked immunosorbent assay (ELISA) and analyzed the features of MAPK and NFκB signaling pathway by western blot. To analyse the effects of PGE2 on uterine smooth muscle cells, we isolated and cultured uterine smooth muscle cells, and analysed the effect of PGE2 on the expression and nuclear translocation of NFκB p65 by western blot and laser confocal microscope.Our results showed that the expression of PGHS-2 was different between preterm labour and term labour. The expression of PGHS-2 was significantly higher in TL than PTL, and significantly lower in TNL than PTNL. Our results suggested that regulation of PGHS-2 in uterine smooth muscle cells may be different between preterm labour and term labour. We found that the MAPK signaling pathway in myometrium of PTNL was significantly activated compared to TNL. However, the there seemed no significant differernce in activation of NFkB signaling pathway between TNL and PTNL. Compared with term pregnancy, the level of PGE2 was significantly elevated in myometrial of preterm pregnant by ELISA. Therefore, we suggested that the expression of PGHS-2 increased in myometrium of preterm pregnancy through the MAPK signaling pathway rather than the NFκB signaling pathway, while the increased expression of PGHS-2 promoted synthesis of prostaglandin in myometrium. We isolated and cultured uterine smooth muscle cells, and found that PGE2 could significantly inhibit the expression and nuclear translocation of NFκB p65.