Increase in prostaglandin bioavailability precedes the onset of human parturition

Romero, Roberto; Muñoz, H.; Gomez, Ricardo; Parra, M.; Polanco, M.; Valverde, Victor; Hasbún, J; Garrido, Jaime Moreno; Ghezzi, Fabio; Mazor, Moshe; Tolosa, Jorge E.; Mitchell, Murray D.

doi:10.1016/s0952-3278(96)90015-0

Cited by 124 publications

(55 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An increase in PG output precedes the onset of clinical labour (Romero et al 1996, Brown et al 1998 and, importantly, drugs that inhibit PG production have been used clinically to attenuate the progression of labour (Besinger et al 1991), whilst the administration of exogenous PGs induces labour and delivery (Ray & Garite 1992). The rate-limiting and committing step of PG synthesis is catalysed by the cyclooxygenase (COX) enzymes.…”

Section: Nf-kb Is Required For Prostaglandin Synthesismentioning

confidence: 99%

The role of nuclear factor kappa B in human labour

Lindström

Bennett²

2005

Reproduction

272

237

View full text Add to dashboard Cite

Preterm birth remains the leading cause of perinatal mortality and morbidity, largely as a result of a poor understanding of the precise mechanisms controlling labour onset in humans. Inflammation has long been recognised as a key feature of both preterm and term labour, with an influx of inflammatory cells into the uterus and elevated levels of pro-inflammatory cytokines observed during parturition. Nuclear factor kappa B (NF-kB) is a transcription factor family classically associated with inflammation. Accumulating evidence points to a role for NF-kB in the physiology and pathophysiology of labour. NF-kB activity increases with labour onset and is central to multiple pro-labour pathways. Premature or aberrant activation of NF-kB may thus contribute to preterm labour. The current understanding of NF-kB in the context of human labour is discussed here.

show abstract

Section: Nf-kb Is Required For Prostaglandin Synthesismentioning

confidence: 99%

The role of nuclear factor kappa B in human labour

Lindström

Bennett²

2005

Reproduction

272

237

View full text Add to dashboard Cite

show abstract

“…Elevated uterine PGs or enhanced sensitivity of the myometrium to PGs leads to contractions and labour (Romero et al 1996, Challis et al 2000. Among the family of PGs, PGF2A increases the intracellular calcium concentration by stimulating the release of stored calcium, which produces a phasic contraction that permits blood flow to the foetus between contractions and optimises the ability of the uterus to expel the foetus (Luckas et al 1999).…”

Section: Introductionmentioning

confidence: 99%

Prostaglandin F2α regulates the expression of uterine activation proteins via multiple signalling pathways

Xu¹,

You²,

Liu³

et al. 2015

Reproduction

View full text Add to dashboard Cite

Prostaglandin F2a (PGF2A) has multiple roles in the birth process in addition to its vital contractile role. Our previous study has demonstrated that PGF2A can modulate uterine activation proteins (UAPs) in cultured pregnant human myometrial smooth muscle cells (HMSMCs). The objective of this study was to define the signalling pathways responsible for PGF2A modulation of UAPs in myometrium. It was found that PGF2A stimulated the expression of (GJA1) connexin 43 (CX43), prostaglandin endoperoxide synthase 2 (PTGS2) and oxytocin receptor (OTR) in cultured HMSMCs. The inhibitors of phospholipase C (PLC) and protein kinase C (PKC) blocked PGF2A-stimulated expression of CX43. The inhibitors of ERK, P38 and NFkB also blocked the effect of PGF2A on CX43 expression, whereas PI3K and calcineurin/nuclear factor of activated T-cells (NFAT) pathway inhibitors did not reverse the effect of PGF2A on CX43. For PTGS2 and OTR, PLC, PI3K, P38 and calcineurin/NFAT signalling pathways were involved in PGF2A action, whereas PKC and NFkB signalling were not involved. In addition, PGF2A activated NFAT, PI3K, NFkB, ERK and P38 signalling pathways. Our data suggest that PGF2A stimulates CX43, PTGS2 and OTR through divergent signalling pathways.

show abstract

“…They inferred from these data that prostaglandin formation was a consequence of labour. However, studies where sequential amniocentesis was performed, on patients before and during labour, showed that increased prostaglandin concentrations preceded the onset of labour (Romero et al 1996).…”

Section: Introductionmentioning

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

130

View full text Add to dashboard Cite

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.

show abstract

Increase in prostaglandin bioavailability precedes the onset of human parturition

Cited by 124 publications

References 17 publications

The role of nuclear factor kappa B in human labour

The role of nuclear factor kappa B in human labour

Prostaglandin F2α regulates the expression of uterine activation proteins via multiple signalling pathways

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

Contact Info

Product

Resources

About