Possible dual roles for prostacyclin in human pregnancy and labor

Abstract

During pregnancy, the muscular layer of the uterine wall known as the myometrium, which is composed mainly of smooth muscle cells, is maintained in a state of relative quiescence. A switch from myometrial quiescence to myometrial activation is required to establish uterine contractions during labor. Researchers have long been perplexed by the fact that the major prostaglandin produced by the uterus just prior to labor, prostacyclin, is a smooth muscle relaxant. In this issue of the JCI, Fetalvero et al. provide data that they propose explains this paradox, at least in part (see the related article, doi:10.1172/JCI33800). The authors examined uterine tissue from pregnant women near term and found that prostacyclin stimulation, which raises cAMP levels that were previously thought to affect only myometrial quiescence, can promote myometrial activation over time by increasing the expression of a select group of proteins thought to be indicative of a uterine contractile state.

Elevated prostacyclin biosynthesis in mice impacts memory and anxiety-like behavior

“…Prostacyclin mediates biological actions through its G-protein-coupled receptor (IP receptor), where it is known to cause vasodilation and anti-platelet aggregation as one of the major vasoprotectors [1, 2] and the endocrine systems [3, 4], and is used as a vascular protective agent and treatment option in pulmonary hypertension [5, 6]. Although PGI 2 is known to be generated in cerebral arteries [7, 8], the consequences of increased PGI 2 secretion within central nervous system (CNS) have not been extensively characterized.…”

International Union of Basic and Clinical Pharmacology. LXXXIII: Classification of Prostanoid Receptors, Updating 15 Years of Progress

“…Prostacyclin synthase and IP receptor expression are increased during the menstrual phase (Battersby et al, 2004), indicating a possible role in normal and/or dysfunctional menstruation. Perhaps a better case could be made for PGI 2 participation in pregnancy and labor by upregulating contractile proteins and connexin 43 that could prime the myometrium for parturition (Fetalvero et al, 2008;Taggart et al, 2008). IP receptors have also been implicated in preimplantation embryo development (Huang et al, 2007a) and may contribute to embryo transport by decreasing the amplitude of oviductal contractility (Arbab et al, 2002).…”

Physiological roles of connexins in labour and lactation

“…The stimulatory effect of PGF2a on the uterine activation proteins is enhanced in combination with IL1ß (Xu et al 2013). Although PGF2a dose-dependently increased the uterine activation proteins, including CX43 (Xu et al 2013), the most highly expressed prostaglandin in human myometrium is PGI2 (Omini et al 1979), which is normally known as a smooth muscle relaxant (Taggart et al 2008). In the pregnant human myometrium at term, however, PGI2 mediates upregulation of CX43 and contractile proteins such as SM-MHC and a-SMA via activating PKA in human myometrial cells in vitro, resulting in an enhanced contractile response to oxytocin (Fetalvero et al 2008).…”