Nitric oxide synthase activity and localization do not change in uterus and placenta during human parturition

Thomson, Andrew J.; Telfer, Joan F.; Kohnen, Gaby; Young, Anne; Cameron, Iain; Greer, Ian A.; Norman, Jane E.

doi:10.1093/humrep/12.11.2546

Cited by 72 publications

(63 citation statements)

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“…This interaction may play a critical role in the control of cervical ripening and parturition (2,6,26). Our data showed the expression of the iNOS, eNOS and COX-2, which have been suggested as mediators of formation of during gestation, parturition and postpartum in pregnant rat uterine.…”

Section: Discussionsupporting

confidence: 56%

The changes of Inducible Nitric Oxide Synthase, Endothelial Nitric Oxide Synthase and Cyclooxygenase-2 mRNA expressions in intrauterine tissues of pregnant rats

YAR¹

2012

Ankara Üniversitesi Veteriner Fakültesi Dergisi

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Summary: Prostaglandins (PGs) are produced by the intrauterine tissues of pregnancy and play important role in all of the physiological processes of parturition. PGs are synthesized from arachidonic acid by the action of cyclooxygenase (COX). Nitric oxide (NO) is a potent smooth muscle relaxant and is considered to be an important local mediator that suppresses uterine contractility. There may be an interaction between the NO and PG pathways in regulating the nitric oxide synthase (NOS) and COX expression and this interaction may play a critical role in the control of cervical ripening and parturition. The purpose of this study is to examine the expression of cyclooxygenase-2 (COX-2), inducible NOS (iNOS) and endothelial NOS (eNOS) mRNA levels during gestation, parturition, and postpartum in pregnant rat uterus. Forty-two pregnant Sprague Dawley rats were randomly divided into 7 groups. Both uterine horns were removed and the pups and placentas were discarded. Complementary DNA (cDNA) was synthesized after isolation of total RNA from the tissues. The relative expression of iNOS, eNOS and COX-2 genes were measured by quantitative real-time polymerase chain reaction (QRT-PCR). The mRNA level of iNOS was increased during gestation; highest level in parturition and then it decreased at postpartum. The eNOS mRNA level was generally low during gestation in all groups and was significantly increased at postpartum. The COX-2 mRNA levels decreased as the pregnancy progressed to term with the highest level occurring on day 21 and the lovest levels during the postpartum period. In conclusion, there may be an interaction between the NO and PG pathways in cervical ripening and parturition. These results may show that mRNA levels of eNOS, iNOS and COX-2 genes may be effective cervical ripening during pregnancy and parturition.Key words: cyclooxygenase-2, gestation, intrauterine tissue, nitric oxide synthase, parturition. Gebe ratların rahim içi dokularında Uyarılabilir Nitrik Oksit Sentaz, Endotelyal Nitrik Oksit Sentaz ve Siklooksijenaz-2 mRNA ekspresyon değişiklikleriÖzet: Prostaglandinler (PG) gebelikte rahim içi dokularda üretilirler ve doğum sırasındaki tüm fizyolojik süreçlerde önemli rol oynarlar. PG'ler araşidonik asitten siklooksijenaz (COX) enziminin aktivitesi ile sentezlenirler. Nitrik oksit (NO) güçlü bir düz kas gevşetici ve uterus kasılmasını baskılayan önemli bir bölgesel ara bulucu olarak kabul edilir. Nitrik oksit sentaz (NOS) ve COX ifadelenmesinin düzenlenmesinde NO ve PG yolakları arasında bir etkileşim olabilir ve bu etkileşim servikal olgunlaşma ve doğumun kontrolünde kritik bir rol oynayabilir. Bu çalışmanın amacı, hamile rat uterusunda gebelikte, doğum sırasında ve doğum sonrasında siklooksijenaz-2 (COX-2), uyarılabilir NOS (iNOS) ve endotelyal NOS (eNOS) mRNA düzeylerini incelemektir. Kırk iki hamile Sprague Dawley rat rastgele olarak 7 gruba ayrıldı. Her iki uterin boynuzu ve yavrular ve plasenta çıkarıldı. Tamamlayıcı DNA (cDNA) dokulardan total RNA izole edildikten sonra sentezlendi. iNOS, eNOS v...

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Section: Discussionsupporting

confidence: 56%

The changes of Inducible Nitric Oxide Synthase, Endothelial Nitric Oxide Synthase and Cyclooxygenase-2 mRNA expressions in intrauterine tissues of pregnant rats

YAR¹

2012

Ankara Üniversitesi Veteriner Fakültesi Dergisi

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“…In animal experiments, NOS activity decreases significantly from pregnancy to term [7], and is significantly lower on the last day of gestation [8,9]. However, NOS activity and localization do not change in uterus and placenta during human parturition [24]. Di Iulio et al [25] failed to demonstrate any biochemical evidence of a change in NOS activity in human fetal membranes investigated before or after labor.…”

Section: Discussionmentioning

confidence: 98%

Maternal Circulating Nitrite Levels Are Decreased in both Normal Normotensive Pregnancies and Pregnancies with Preeclampsia

Hata

Hashimoto

Kanenishi

et al. 1999

Gynecol Obstet Invest

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Objective: To evaluate whether maternal nitric oxide synthesis in pregnancies with preeclampsia is different from that in normal normotensive pregnancies. Materials: Maternal circulating combined nitrate and nitrite levels or nitrite level were compared between 10 normotensive nonpregnant women, 30 normotensive pregnant women (10 first-trimester, 10 second-trimester, and 10 third-trimester pregnancies), 20 normotensive postpartum women (10 at 1 week after delivery, and 10 at 4 weeks after delivery), and 13 preeclamptic women (32 to 40 weeks’ gestation). End-products of nitric oxide synthesis were measured from maternal venous blood samples using a fluorometric assay. Results: Maternal circulating nitrite levels in nonpregnant women (1.13 ± 0.22 μM) were significantly higher than those in the first-trimester pregnant women (0.68 ± 0.13 μM), second-trimester pregnant women (0.65 ± 0.13 μM), third-trimester pregnant women (0.48 ± 0.17 μM), first puerperal week women (0.36 ± 0.16 μM), and fourth puerperal week women (0.67 ± 0.17 μM), respectively (p < 0.05). Maternal circulating nitrite level was decreased with advancing gestation, still remained low just after delivery, and was increased 4 weeks later. There was no significant difference in maternal circulating nitrite level between preeclamptic women (0.40 ± 0.17 μM) and third-trimester pregnant women (0.48 ± 0.17 μM). However, there were no significant differences in maternal circulating combined nitrate and nitrite levels among the gorups. Conclusion: These results suggest that the maternal nitric oxide synthesis is not changed in normal normotensive pregnancies and pregnancies with preeclampsia. However, plasma nitrite level, which has stronger spasmolytic activity than the activity of the nitrate, was decreased in both normal normotensive pregnancies and pregnancies with preeclampsia.

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“…Recent studies of NOS enzymes and also superoxide dismutase and xanthine oxidase (enzymes that generate superoxide and attenuate NO levels) indicate little change in these systems in human myometrium, fetal membranes and placenta at term labour versus non-labour (Telfer et al, 1997;Thomson et al, 1997b). However, all the samples were obtained at term, at a time when the levels of the enzymes might already have decreased.…”

Section: Figurementioning

confidence: 99%

Control and assessment of the uterus and cervix during pregnancy and labour

Garfield

Saade²,

Buhimschi

et al. 1998

Human Reproduction Update

188

129

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Preterm labour and resultant preterm birth are the most important problems in perinatology. Countless efforts have failed to establish a single effective treatment of preterm labour, partly because the mechanisms regulating the uterus and cervix during pregnancy are not well understood. New knowledge is needed to inhibit early progression of labour (uterine contractility and cervical ripening), and adequate quantitative tools to evaluate the uterus and cervix during pregnancy are lacking. In this review, we outline studies showing that the uterus (myometrium) and cervix pass through a conditioning step in preparation for labour. This step is not easily identifiable with present methods to assess the uterus or cervix. In the uterus, this seemingly irreversible step consists of changes in the electrical properties to make muscle more excitable and responsive to produce forceful contractions. In the cervix, the step consists of softening of the connective tissue components. Progesterone appears to have a dominant role in controlling both the uterus and cervix, as antiprogestins induce early, preterm conditioning leading to preterm labour. Apparently, nitric oxide (NO) also controls conditioning of the uterus and cervix. In the uterus, NO, in concert with progesterone, inhibits uterine contractility. At term, NO production by the uterus and placenta are decreased and allow labour to progress. In contrast, NO in the cervix increases at the end of pregnancy and it may be the final pathway for stimulating cervical ripening by activation of metalloenzymes. The progress of labour can be assessed non-invasively using electromyographic (EMG) signals from the uterus (the driving force for contractility) recorded from the abdominal surface. Uterine EMG bursts detected in this manner characterize uterine contractile events during human and animal pregnancy. A low uterine EMG activity, measured transabdominally throughout most of pregnancy, rises dramatically during labour. EMG activity also increases substantially during preterm labour in humans and rats. This method may be used one day to predict impending preterm labour and identify control steps and treatments. A quantitative method also assesses the cervix, using an optical device which measures collagen fluorescence in the cervix. The collascope estimates cervical collagen content from a fluorescent signal generated when collagen cross-links are illuminated with excitation light of about 340 nm. The system has proved useful in rats and humans at various stages of pregnancy, and indicates that cervical softening occurs progressively in the last one-third of pregnancy. In rats, collascope readings correlate with resistance measurements made in the isolated cervix, which may help to assess cervical function during pregnancy, and indicate control and treatments.

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Nitric oxide synthase activity and localization do not change in uterus and placenta during human parturition

Cited by 72 publications

References 0 publications

The changes of Inducible Nitric Oxide Synthase, Endothelial Nitric Oxide Synthase and Cyclooxygenase-2 mRNA expressions in intrauterine tissues of pregnant rats

The changes of Inducible Nitric Oxide Synthase, Endothelial Nitric Oxide Synthase and Cyclooxygenase-2 mRNA expressions in intrauterine tissues of pregnant rats

Maternal Circulating Nitrite Levels Are Decreased in both Normal Normotensive Pregnancies and Pregnancies with Preeclampsia

Control and assessment of the uterus and cervix during pregnancy and labour

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