Mechanism for Increased Production of Prostaglandins in Labour

Batra, Satish; Bengtsson, L.G.

doi:10.1016/s0140-6736(76)91547-6

Cited by 21 publications

(4 citation statements)

References 25 publications

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“…Prostaglandin F2α (PGF2α), like oxytocin, is a major stimulator of uterine activity in labor (22). Hypoxia has been shown to up-regulate COX2 and increase prostaglandin production in smooth muscle and other tissues (23,24), and this has been hypothesized to contribute to labor (25). We therefore investigated the effects of inhibiting prostaglandin biosynthesis on HIFI by blocking the cyclo-oxygenases.…”

Section: Cox2 and Intracellular Camentioning

confidence: 99%

Hypoxia-induced force increase (HIFI) is a novel mechanism underlying the strengthening of labor contractions, produced by hypoxic stresses

Alotaibi

Arrowsmith

Wray

2015

Proc. Natl. Acad. Sci. U.S.A.

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For successful birth, contractions need to become progressively stronger. The underlying mechanisms are unknown, however. We have found that a novel mechanism, hypoxia-induced force increase (HIFI), is switched on selectively, at term, and is essential to strengthening contractions. HIFI is initiated as contractions cyclically reduce blood flow and produce repeated hypoxic stresses, with associated metabolic and transcriptomic changes. The increases in contractility are a long-lasting, oxytocin-independent, intrinsic mechanism present only in the full-term pregnant uterus. HIFI is inhibited by adenosine receptor antagonism and blockade of cyclooxygenase-2 signaling, and partially reproduced by brief episodes of acidic (but not alkalotic) pH. HIFI explains how labor can progress despite paradoxical metabolic challenge, and provides a new mechanistic target for the 1 in 10 women suffering dysfunctional labor because of poor contractions. myometrium | smooth muscle | pH | hypoxia | hypoxic preconditioning P ulsatile releases of oxytocin are important for labor, but as oxytocin knockout mice deliver normally (1), other mechanisms for increasing contractile strength must occur. A puzzling feature of labor is that contractions become progressively stronger as the myometrium (uterine muscle) experiences repetitive metabolic stress from hypoxia. This reaction occurs because as contractions develop they briefly compress the uterine blood vessels (2, 3). Transient decreases of oxygenation, pH, and ATP, all of which if sustained can decrease contractile activity, occur in vivo with each contraction (3-5). Hypoxia regulates a large number of genes, including those governing metabolism and function in many tissues, and changes in genes associated with hypoxia have been identified as key findings in transcriptomic studies of poorly laboring women (6, 7). Chaemsaithong et al. and Mittal et al. confirmed changes in hypoxia-inducible factor 1a (HIF1a) using RT-PCR, as well as overexpression of cyclooxygenase-2 (COX2) in myometrium and endothelial NOS, which is important for blood vessel dilation. There is, however, no empirical evidence showing how such changes could be important to successful labors, and no existing mechanism linking hypoxia to an increase in contractions. In contrast, studies of hypoxia in myometrium and other smooth muscles show it to decrease contractility (8, 9).Of note, however, are studies demonstrating ischemic tolerance as an adaptive response initiated by several exposures to a stressor of mild severity, from which resistance to ischemia is markedly increased. This is known as hypoxic or ischemic preconditioning, and has been best investigated in cardiac muscle (10) and brain (11), where it is considered to be a powerful mechanism for limiting ischemic damage. Given that physiological decreases in oxygenation are part of the normal process of labor (4, 12), this finding therefore raised some important questions: What is the effect of brief but repetitive periods of hypoxia on uterine contractility? And...

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Section: Cox2 and Intracellular Camentioning

confidence: 99%

Hypoxia-induced force increase (HIFI) is a novel mechanism underlying the strengthening of labor contractions, produced by hypoxic stresses

Alotaibi

Arrowsmith

Wray

2015

Proc. Natl. Acad. Sci. U.S.A.

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“…However, NAG activity requires a low p H environment, and it is uncertain whether or not the cervix in late pregnancy is acidic. Barta & Bengtsson proved that uterine contractions cause uterine hypoxia in late pregnancy (12). Thus, it would seem likely that the condition of the uterine cervix in late pregnancy is acidic, due to an accumulation of lactic acid.…”

Section: Discussionmentioning

confidence: 99%

An enzyme (β‐D‐N‐acetylglucosaminidase) released from the decidua to maternal plasma prior to the onset of labor

Takenaka

Soga

Miyamoto

et al. 1991

Acta Obstet Gynecol Scand

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Changes in the activity of beta-N-acetylglucosaminidase (E.C. 3.2.1.30; NAG), a lysosomal marker enzyme, in the maternal plasma and utero-placental tissues during late pregnancy and parturition were examined in order to determine if lysosomal enzymes participate in the cervical ripening. NAG activity in the plasma gradually increased as gestation advanced, to reach a maximum 3-4 days before the spontaneous onset of labor, and remaining at this level until the second stage. The activity measured in decidua and amnion obtained from the women who had undergone routine repeat cesarean section after labor onset was lower than in those before the onset. Since the decidua was much heavier than the amnion, it was concluded that NAG was released to the maternal circulation mainly from the decidua and only partly from the amnion. Our data revealed that lysosomal enzyme release occurs prior to the onset of labor, and that NAG may play a role primarily in the ripening of the cervix rather than in the onset of labor, by hydrolysing GAGs in the uterine cervix.

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“…It has been suggested that all myometrial stimulants manifest their action by the production or liberation of prostaglandins (PG) (Csapo & Csapo, 1974; see also Batra & Bengtsson, 1976). The present study was designed to examine further the uterine sensitivity to vasopressin and oxytocin at different endocrine conditions and to investigate the extent to which the difference in the effect of the two polypeptides can be explained by a mechanism involving PGs.…”

Section: Introductionmentioning

confidence: 98%

Differences in the effects of vasopressin and oxytocin on rabbit myometrial activity and a possible mediation of prostaglandins

Laudański¹,

Åkerlund²,

Batra³

1977

Reproduction

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Uterine responses to vasopressin and oxytocin were monitored in non-pregnant and 3- or 6-8-day-pregnant rabbits by recording the intrauterine pressure. Oxytocin stimulated uterine activity in all groups, but the effect of vasopressin was stimulatory in non-pregnant animals, inhibitory in those 3 days post coitum and weakly stimulatory in those later in pregnancy. Inhibition of prostaglandin (PG) synthesis, by the administration of indomethacin, reduced the spontaneous uterine activity as well as the responses to oxytocin and vasopressin in the non-pregnant rabbits, but had little effect in the pregnant animals. During infusion of PGF-2alpha, PGE-1 or PGE-2 in 6-8-day-pregnant rabbits, the stimulatory response to vasopressin, although slight before the infusion, was inhibited whereas the stimulatory response to oxytocin remained virtually unchanged. The results suggest that vasopressin and oxytocin under certain hormonal conditions, are able to activated the uterine contractions by mechanisms in which the involvement of PG is not obligatory.

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Mechanism for Increased Production of Prostaglandins in Labour

Cited by 21 publications

References 25 publications

Hypoxia-induced force increase (HIFI) is a novel mechanism underlying the strengthening of labor contractions, produced by hypoxic stresses

Hypoxia-induced force increase (HIFI) is a novel mechanism underlying the strengthening of labor contractions, produced by hypoxic stresses

An enzyme (β‐D‐N‐acetylglucosaminidase) released from the decidua to maternal plasma prior to the onset of labor

Differences in the effects of vasopressin and oxytocin on rabbit myometrial activity and a possible mediation of prostaglandins

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