Role of fetal membranes in signaling of fetal maturation and parturition

Abstract

The fetal membranes fulfill several functions during pregnancy. In addition to containing the products of conception and amniotic fluid, they presumably have barrier functions and fulfill paracrine signaling functions between the maternal (decidual) and fetal compartments. As the membranes are in an ideal place to receive both maternal and fetal signals and transmit signals to uterine myometrium, there has been a specific focus on the role of membranes in the initiation and maintenance of parturition. In this review, we summarize the data obtained in our laboratories as well as the data reported in the literature particularly with regard to the synthesis of steroids and prostaglandins in the fetal membranes, in signaling fetal maturation and in parturition. The fetal membranes are a major site both of prostaglandin synthesis and of prostaglandin metabolism. In addition, the abundant expression of 11beta-hydroxysteroid dehydrogenase 1 (11β β β β β-HSD1), which converts biologically inactive cortisone into active cortisol, in the fetal membranes may provide an extra-adrenal source of glucocorticoids for the fetal compartment during gestation. Accumulating evidence indicates that a positive feedback loop involving glucocorticoids, proinflammatory cytokines, prostaglandins, surfactant protein-A (SP-A) and 11β β β β β-HSD1 is formed locally in human fetal membranes towards term or in preterm labor. This positive feedback loop would produce abundant biologically active glucocorticoids and prostaglandins in the fetal membranes or amniotic fluid, which would ultimately promote fetal organ maturation and initiate parturition. KEY WORDS: fetal membrane, prostaglandin, glucocorticoid, fetus, parturitionAt term the human fetal membranes comprised of amnion and chorion tissue layers are approximately 1000-1200cm 2 in area with 30% of this overlying the placenta and the remaining 70% being the reflected membranes that interact with decidua. The fetal surface of the membranes is composed of a single layer of amnion epithelium supported by a basement membrane resting on a thick collagen layer containing fibroblasts. The ratio of epithelial cells to fibroblasts in amnion is approximately 10 to 1. A thin spongy layer connects the collagen layer to the chorion leave comprised of cytotrophoblasts and these trophoblasts contact the decidua. The fetal membranes fulfill several functions during pregnancy. In addition to containing the products of conception and amniotic fluid, they presumably have barrier functions and fulfill paracrine signaling functions between the maternal (decidual) and fetal compartments. Unlike many animals the human fetal membranes are not vascularized which probably severely limits their functioning as an exchange surface for nutrients Int. J. Dev. Biol. 54: 545-553 (2010) doi: 10.1387/ijdb.082771lm between mother and fetus. As the membranes are in an ideal place to receive both maternal and fetal signals and transmit signals to uterine myometrium there has been a specific focus on the role of mem...

11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action

“…Fetal membranes also express 11␤-HSD. In the human amnion, 11␤-HSD1 is concentrated in fibroblasts where expression is increased by glucocorticoids and cytokines (681), providing a feed-forward loop (506). Here, glucocorticoids increase prostaglandin E 2 production, which is central to the induction of parturition.…”

Polyunsaturated fatty acids modulate prostaglandin synthesis by ovine amnion cells in vitro

“…It is generally accepted that the onset of labour in most mammalian species including sheep is associated with an increase in n-6-derived two-series PGs , Olson 2003, Myatt & Sun 2010 produced by the intrauterine tissues (placenta, amnion, chorion, decidua/ endometrium and myometrium) (sheep: Rice et al 1990, 1995, Thorburn 1991, McLaren et al 1996, 2000guinea pig: Welsh et al 2005;human: Slater et al 1999, Sawdy et al 2000. Rats, humans and sheep fed a high n-6 PUFA diet have been shown to have shortened pregnancies (Olsen & Secher 1990, Olsen et al 1991, Elmes et al 2005, while animals (e.g.…”

“…The observation that the ovine amnion contained greater PLA 2 activity than either the myometrium or the placenta (Grieves & Liggins 1976) and that induction of labour with corticotrophin induced a marked increase in amniotic PLA 2 activity (Grieves & Liggins 1976) provides further evidence to support a role for PLA 2 -derived AA, 20:4, n-6 metabolism to two-series PGs in inducing ovine parturition. Of the many different isoforms of PLA 2 , a 85 kDa cytosolic PLA 2 (cPLA 2 ) has been localised within the human amnion (Myatt & Sun 2010), and its pivotal role in parturition has been amply demonstrated by the fact that cPLA 2 null mice were unable to deliver offspring (Uozumi et al 1997).…”

Estrogen metabolites in the release of inflammatory mediators from human amnion-derived cells

“…During pregnancy amnion cells produce inflammatory mediators including cytokines, arachidonic acid (AA) and prostaglandins (PGs) in response to autocrine, paracrine and endocrine signals (Myatt and Sun 2010). PGs released by amnion cells represent a key event to trigger uterine contractions (Blickstein 2009).…”

“…Therefore, WISH cells could be useful for in vitro studies about the molecular effects exerted during pregnancy by steroid hormones and their metabolites, that show important biological activity in inflammatory processes (Straub 2007). It is indeed known that cortisol, estrogens, progesterone, as well as endogenous estrogen metabolite levels increase in amniotic fluid during pregnancy (Myatt and Sun 2010). Catechol estrogens can moreover participate in the process of implantation and in the initiation of labor, being able to stimulate the synthesis of prostaglandins (Biswas et al 1991a,b).…”