The Initiation and Inhibition of Labor - Toward a Molecular Understanding

Lye, Stephen J.

doi:10.1055/s-2007-1016409

Cited by 52 publications

(22 citation statements)

References 86 publications

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“…At term these changes reverse to allow the uterus to contract, and the cervix to soften and dilate. Lye (1994) has suggested that labour is the result of the activation of a 'cassette of contraction associated proteins' which might include gap junction proteins, oxytocin and prostaglandin receptors. We have previously shown that, at the mRNA level, it is principally COX-2 which is expressed in both amnion and chorion-decidua, and that its expression increases with the onset of labour, whilst the expression of COX-1 in both tissues is unchanged (Slater et al 1995(Slater et al , 1998.…”

Section: Discussionmentioning

confidence: 99%

Expression of cyclo-oxygenase types-1 and -2 in human fetal membranes throughout pregnancy

Slater

Dennes²,

Sawdy³

et al. 1999

Journal of Molecular Endocrinology

129

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Human labour is associated with increased prostaglandin synthesis within the fetal membranes. We have studied the expression of the two isoforms of the central prostaglandin synthetic enzyme, cyclooxygenase (COX-1 and COX-2), in human fetal membranes throughout pregnancy, at mRNA, protein and activity levels.COX-1 mRNA expression was low in human amnion and chorion-decidua and did not change with gestational age. COX-2 mRNA expression in fetal membranes increased with gestational age, with significant up-regulation prior to the onset of labour and in association with labour. Protein concentrations of COX-1 did not change, whilst concentrations of COX-2 increased from the first to the third trimester. COX activity increased with gestational age and in association with labour, although prostaglandin production in fetal membranes collected after labour was reduced, suggesting reduced substrate supply.These data suggest that it is up-regulation of COX-2, rather than of COX-1, which mediates increased prostaglandin synthesis within the fetal membranes at term. Much of the increase in COX-2 expression precedes the onset of labour, suggesting that it is a cause, rather than a consequence, of labour.

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Section: Discussionmentioning

confidence: 99%

Expression of cyclo-oxygenase types-1 and -2 in human fetal membranes throughout pregnancy

Slater

Dennes²,

Sawdy³

et al. 1999

Journal of Molecular Endocrinology

129

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“…Estrogen, in turn, stimulates intrauterine PG production (16,17). It also triggers the expression of contraction-associated proteins within the myometrium, leading to labor and delivery of the fetus (19). However, recent evidence suggests two separate pathways for the production of PGs: a cortisol-dependent/estrogen-independent pathway within the fetal placental trophoblast tissue and an estrogendependent pathway within the maternal intrauterine tissue (31).…”

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confidence: 99%

Effects of periconceptional undernutrition on the initiation of parturition in sheep

Kumarasamy

Mitchell²,

Bloomfield³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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In sheep, parturition is initiated by increased fetal hypothalamic-pituitary-adrenal axis (HPAA) activity leading to PGE2 and PGF2␣ production and a rise in the 17␤-estradiol-progesterone (E 2/P4) ratio. Uteroplacental PG production can also increase fetal HPAA activity. Periconceptional maternal undernutrition accelerates fetal HPAA maturation resulting in preterm labor. We determined whether preterm labor was preceded by an increase in PG concentrations and E 2/P4 ratio and whether these increases preceded or followed the corresponding rise in cortisol concentrations. Singleton-bearing ewes were nourished ad libitum (N, n ϭ 9) or undernourished (UN, n ϭ 10) to reduce maternal weight by 15% from Ϫ61 days (d) to ϩ30 d after mating with ad libitum intake thereafter. Paired maternal and fetal blood samples were collected from 126 d until delivery. Half the UN group delivered prematurely (Ͼ2 SD below mean gestation for the flock). PG and cortisol concentrations and E 2/P4 ratio increased before delivery in the same way in both groups. However, the increases occurred 7-10 d earlier in UN than in N animals. In both UN and N fetuses cortisol concentrations rose before fetal and maternal PG concentrations and maternal E 2/P4 ratio. Periconceptional maternal undernutrition induces preterm delivery in sheep by advancing the expected prepartum rise in cortisol and PG concentrations and E 2/P4 ratio. The rise in fetal cortisol concentration precedes the rise in fetal and maternal PG concentrations and maternal E 2/P4 ratio, suggesting that the underlying mechanism is likely to be acceleration of fetal HPAA maturation, resulting in initiation of the normal process of parturition.hypothalamic-pituitary-adrenal axis; prostaglandin; cortisol; estrogenprogesterone ratio

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“…This switch is accompanied by myometrial activation (Lye 1994) involving changes in expression of a collection of contraction-associated proteins, such as estrogen receptor (Wu et al 1995), gap junctions (Garfield 1988, Lye et al 1993) and oxytocin receptor (Fuchs et al 1983, Wu & Nathanielsz 1994, Zingg et al 1995, Chen et al 1996. Each member of the cassette of genes contributes to some extent in the switch in myometrial contractility patterns from contractures to contractions as well as the progression of established labor.…”

Section: Introductionmentioning

confidence: 99%

“…A major focus has been on the effects of the two steroid hormones, estrogen and progesterone, on the expression of myometrial contraction associated proteins (Lye 1994, Wu et al 1996a. In this study we examined the regulatory control of estrogen and progesterone on expression of myometrial DSCR1 and TCTE1L mRNA in the ovariectomized non-pregnant sheep.…”

Section: Introductionmentioning

confidence: 99%

Characterization of two labor-induced genes, DSCR1 and TCTE1L, in the pregnant ovine myometrium

Wen

H²,

Q³

et al. 2003

Journal of Endocrinology

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In the present study we characterized two labor-induced genes, DSCR1 (Down syndrome candidate region 1) and TCTE1L (murine t-complex like), which were identified by suppression subtractive hybridization in the pregnant ovine myometrium. DSCR1 and TCTE1L cDNA sequences were retrieved from a custom-made labormyometrial cDNA library by hybridization screening. The characterized cDNA sequences include 5 -untranslated region (UTR), coding region and 3 -UTR, which are 12 bp, 351 bp and 1716 bp for TCTE1L, and 64 bp, 594 bp and 1539 bp for DSCR1 respectively. The two cDNA sequences encode proteins of 116 and 197 amino acids for TCTE1L and DSCR1 respectively. Northern analysis further confirmed the significant increases of myometrial DSCR1 and TCTE1L mRNA associated with spontaneous term labor (n=6) compared with gestation-matched controls not in labor (n=6). The abundance of DSCR1 and TCTE1L mRNA was attenuated when myometrial contraction was inhibited by Nimesulide (n=6), a specific prostaglandin H synthase 2 inhibitor. Fetal occupancy greatly upregulated DSCR1 and TCTE1L mRNA in the gravid horn during betamethasone-induced premature labor (n=6) compared with the non-gravid horn not in labor (n=3). Estradiol upregulated TCTE1L mRNA, but had no effect on DSCR1 mRNA expression in the non-pregnant sheep myometrium. Progesterone alone had no effect on both DSCR1 and TCTE1L mRNA expression, however progesterone antagonized estradiol's stimulating effect on myometrial TCTE1L mRNA expression in ovariectomized non-pregnant sheep.Upregulation of DSCR1 and TCTE1L in both betamethasone-induced premature labor and spontaneous term labor and inhibition of their expression by Nimesulide suggest a functional role of these two genes in myometrial activation associated with onset of labor. Mechanical stretch, labor and steroids differentially regulated DSCR1 and TCTE1L mRNA in the pregnant and non-pregnant sheep myometrium.

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The Initiation and Inhibition of Labor - Toward a Molecular Understanding

Cited by 52 publications

References 86 publications

Expression of cyclo-oxygenase types-1 and -2 in human fetal membranes throughout pregnancy

Expression of cyclo-oxygenase types-1 and -2 in human fetal membranes throughout pregnancy

Effects of periconceptional undernutrition on the initiation of parturition in sheep

Characterization of two labor-induced genes, DSCR1 and TCTE1L, in the pregnant ovine myometrium

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