The molecular basis of labour and tocolysis

Lye, Stephen J.; Ou, Che-Wei; Teoh, Tiong-Ghee; Erb, Grace; Stevens, Yvette; Casper, Robert F.; Patel, Falguni A.; Challis, John

doi:10.1017/s096553959800031x

Cited by 59 publications

(43 citation statements)

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“…Administration of exogenous progesterone at term in the ewe not only inhibits the expression of myometrial CAPs but also blocks the onset of labour (Lye & Porter 1978). Furthermore, functional withdrawal of progesterone in the myometrium induces CAP expression and activates myometrial contractile activity (Lye et al 1998). These data therefore provide some evidence to suggest that the adverse effects of a HFHC diet on myometrial contractile protein expression may be mediated through alterations in steroid synthesis.…”

Section: Discussionmentioning

confidence: 76%

The effects of a high-fat, high-cholesterol diet on markers of uterine contractility during parturition in the rat

Elmes

Tan²,

Cheng³

et al. 2011

Reproduction

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Increasing levels of obesity within women of reproductive age is a major concern in the UK. Approximately, 13% of women aged !30 and 22% of 31-to 40-year-old women are obese. Obesity increases complications during pregnancy and the risk of caesarean section due to prolonged labour and poor uterine activity. The aim was to investigate whether a high-fat, high-cholesterol (HFHC) diet decreases markers of uterine contractility during parturition in the rat. Female Wistar rats were fed control (CON, nZ10) or HFHC (nZ10) diets for 6 weeks. Animals were mated and, once pregnant, maintained on their diet throughout gestation. On gestational day 19, rats were monitored continuously and killed at the onset of parturition. Body and fat depot weights were recorded. Myometrial tissue was analysed for cholesterol (CHOL), triglycerides (TAG), and expression of the contractile associated proteins gap junction protein alpha 1 (GJA1; also known as connexin-43, CX-43), prostaglandin-endoperoxide synthase 2 (PTGS2; also known as cyclo-oxygenase-2, COX-2) and caveolin-1 (CAV1) and maternal plasma for prostaglandin F 2a (PGF 2a ) and progesterone. HFHC fed rats gained greater weight than CON (P!0.003) with significant increases in peri-renal fat (P!0.01). The HFHC diet increased plasma CHOL, TAG and progesterone, but decreased PGF 2a versus CON (P!0.01, P!0.01, PZ0.05 and P!0.02 respectively). Total CHOL and TAG levels of uterine tissue were similar. However, HFHC fed rats showed significant increases in PTGS2 (P!0.037), but decreases in GJA1 and CAV1 (PZ0.059). In conclusion, a HFHC diet significantly increases body weight and alters lipid profiles that correlate with decreases in key markers of uterine contractility. Further work is required to ascertain whether these changes have adverse effects on uterine activity.

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Section: Discussionmentioning

confidence: 76%

The effects of a high-fat, high-cholesterol diet on markers of uterine contractility during parturition in the rat

Elmes

Tan²,

Cheng³

et al. 2011

Reproduction

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“…There are numerous kinds of receptors and ion channels involved in the uterine smooth muscle contraction (Wray, 1993). Though some mechanisms remain to be determined, the molecular mechanism involved in the regulation of labour and myometrial contractions in many species including humans, sheep and cows was substantially elucidated and was reviewed elsewhere (Wray, 1993;Lye et al, 1998;Hirsbrunner et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Gentamycin inhibition of kcl-induced contractions of myometrium isolated from non-pregnant and pregnant cows

Öcal¹,

Yüksel²,

Ayar³

2004

Vet. Med. - Czech

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ABSTRACT:The aim of this study was to investigate the effects of gentamycin on KCl-induced contractions of myometrium isolated from both non-pregnant and pregnant cows. Myometrial strips were isolated from non-pregnant and pregnant cows and suspended in a jacketed organ bath filled with Krebs' solution at 37°C (pH 7.4) continuously bubbled with 95% oxygen and 5% carbon dioxide; isometric contractions were recorded using an isometric force displacement transducer. A�er manifestation of spontaneous contractions, KCl (60 mM) was applied to the bath and the effects of gentamycin (300 µM, 600 µM) on the amplitude (g) and frequency of KCl-induced contractions were evaluated in 10-minute intervals. Data were statistically analysed using Student's t-test and Wilcoxon signed-rank test. Gentamycin inhibited the frequency and amplitude of KCl-induced contractions in a concentration dependent manner. At 300 µM and 600 µM, gentamycin significantly inhibited the amplitude and reduced the frequency of contractions of myometrium isolated from both pregnant and non-pregnant cows. However, an increase in the extracellular Ca + ion concentration virtually reversed this blockade. The results of this in vitro study indicate that gentamycin inhibits KCl-induced contractions of myometrium isolated from both non-pregnant and pregnant cows.

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“…The onset of labor is thought to be due to the gradual coordination of several mechanisms to produce myometrial contractions. 45 Thus, it is likely that other mechanisms in addition to G-protein-cAMP signaling will operate to maintain uterine quiescence.…”

Section: Discussionmentioning

confidence: 99%

Hemoxygenase and Nitric Oxide Synthase Do Not Maintain Human Uterine Quiescence during Pregnancy

Barber¹,

Robson

Lyall³

1999

The American Journal of Pathology

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The nitric oxide (NO)-cGMP pathway has been proposed as a mechanism for relaxation of myometrium during pregnancy and as a modulator of labor. Carbon monoxide (CO) , produced by hemeoxygenases (HO-1 and HO-2) , also activates soluble guanylate cyclase to increase cGMP. A recent study reported a large increase in HO-1 and HO-2 proteins during pregnancy , suggesting that the HO-CO pathway may be important in the maintenance of uterine quiescence during pregnancy. In this study we used Western blotting , reverse transcription-polymerase chain reaction , and immunohistochemistry to determine HO-1 and HO-2 expression in nonpregnant , pregnant, and laboring myometrium. Immunolocalization of HO was also compared with endothelial and inducible nitric oxide synthases (eNOS and iNOS). In contrast to HO-1 protein , which was not detected in myometrium , HO-2 protein and mRNA were constitutively expressed , although there were no differences in expression between the groups. eNOS was expressed in endothelial cells but not in myometrial smooth muscle. iNOS protein was not detected in myometrium. These data do not support an up-regulation of HO-1 and HO-2 during pregnancy and are not consistent with a role for NO or a major role for CO in human myometrial quiescence. Our results are also in keeping with HO-2 being an noninducible protein. Although spontaneous preterm birth (delivery before 37 weeks) accounts for 5 to 10% of all births, it is associated with up to 70% of neonatal deaths. It is also responsible for up to 75% of neonatal morbidity with considerable long-term morbidity in the child. 1-3 Drugs used to treat preterm labor, such as prostaglandin synthesis inhibitors, calcium channel antagonists and ␤-adrenoceptor agonists, have only short-lived effects or have potential side effects for mother and fetus. 4,5 Agents that have been used more recently, such as oxytocin receptor antagonists 6 and nitric oxide (NO) donors, 7 are currently the focus of intensive research, but early reports suggest that they will not confer major benefits. One reason there is no effective method of treating preterm labor is our limited knowledge of the mechanisms that control myometrial quiescence during pregnancy and its contractile state in normal and preterm labor. 8,9 NO, produced by the enzyme nitric oxide synthase (NOS), binds to the heme prosthetic moiety of the soluble guanylate cyclase, leading to increased cGMP production and smooth muscle relaxation. Carbon monoxide (CO) also binds to heme and activates soluble guanylate cyclase. 10 Discrepancies in localization of NOS and guanylate cyclase in the brain indicate that a substantial portion of guanylate cyclase may not serve as a target for NO. 11 CO is produced by heme oxygenase (HO), a microsomal enzyme that oxidatively cleaves heme, a prooxidant, to produce biliverdin and CO in the presence of NADPH-cytochrome P 450 reductase and NADPH. 12 HO consists of two homologous isoenzymes: HO-1, which is inducible, and HO-2, which is constitutive. 13,14 HO-1 is expressed at high concent...

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The molecular basis of labour and tocolysis

Cited by 59 publications

References 0 publications

The effects of a high-fat, high-cholesterol diet on markers of uterine contractility during parturition in the rat

The effects of a high-fat, high-cholesterol diet on markers of uterine contractility during parturition in the rat

Gentamycin inhibition of kcl-induced contractions of myometrium isolated from non-pregnant and pregnant cows

Hemoxygenase and Nitric Oxide Synthase Do Not Maintain Human Uterine Quiescence during Pregnancy

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