Cyclooxygenases in Reproductive Medicine and Biology

Abstract

This reviewfocuses on the role ofcyclooxygenases in reproductive medicine and biology. The cyclooxygenase enzymes catalysis the role-limiting reactions for prostaglandins and thromboxane synthesis. Two separate isoforms, COX-1 and COX-2, are present, and differences in their roles are discussed in the context of inflammation and parturition.

Advanced glycation endproducts mediate pro-inflammatory actions in human gestational tissues via nuclear factor-κB and extracellular signal-regulated kinase 1/2

“…This effect may be both direct (through interaction with RAGE) and/or indirect, via generation of free oxygen radicals. This leads to the production of pro-inflammatory cytokines, growth factors, adhesion molecules and chemokines (Schmidt et al 1994, Hofmann et al 1999, Fiuza et al 2003, Shanmugan et al 2006) that have been implicated in the processes of human labour and delivery (Kniss 1999, Rice 2001, Bowen et al 2002. In isolated human first-trimester trophoblasts, AGE stimulates secretion of chemokines such as macrophage inflammatory protein (MIP)-1a and MIP-1b, induces apoptosis, and suppresses the secretion of human chorionic gonadotrophin, an effect that could be suppressed by inhibitors of NO synthases or the NF-kB pathway (Konishi et al 2004), thus suggesting that reactive nitrogen species as well as ROS contribute to AGE-mediated actions in the human gestational tissues.…”

“…Prostaglandins and pro-inflammatory cytokines, which are produced within the intrauterine environment, participate in the processes of human labour and delivery, specifically the regulation of myometrial contractility, cervical ripening and rupture of membranes (reviewed in Kniss 1999, Rice 2001 . Experimental data from cell culture, animal models and tissue studies have provided evidence that pro-inflammatory cytokines and prostaglandins accumulate in the amniotic fluid and intrauterine tissues of women at the time of labour at term, and they are elevated even further in infection-associated preterm labour.…”

“…Increased intrauterine cytokine and prostaglandin production, which occurs modestly with term labour, is a characterising feature of preterm labour, particularly in the presence of intrauterine infection (Kniss 1999, Rice 2001, Bowen et al 2002. Bacterial colonisation and/or inflammation of the choriodecidual interface induces production of pro-inflammatory cytokines that, in turn, lead to neutrophil activation and the synthesis and release of uterotonins such as prostaglandins, which cause uterine contractions, and metalloproteinases, that weaken fetal membranes and remodel cervical collagen (Rice 2001, Bowen et al 2002.…”

Nanomolar and Micromolar Effects of 15-Deoxy-Δ12,14-prostaglandin J2on Amnion-Derived WISH Epithelial Cells: Differential Roles of Peroxisome Proliferator-Activated Receptors γ and δ and Nuclear Factor κB

“…The presence of intrauterine infection has been shown to result in the local expression and secretion of proinflammatory cytokines such as interleukin (IL)-1␤, tumor necrosis factor-␣, IL-6, and IL-8 (Romero et al, 1993;Dudley et al, 1996;Keelan et al, 1999a), which act locally on intrauterine cells to induce the release of inflammatory mediators, extracellular matrix-remodeling enzymes (So et al, 1992;Draper et al, 1995), and prostaglandins (PGs) through altered expression of prostanoid biosynthetic enzymes including fatty acid cyclooxygenase-2 (COX-2) Hansen et al, 1999;Kniss, 1999;Rauk and Chiao, 2000).…”

Role of Nuclear Receptors Peroxisome Proliferator-Activated Receptors (PPARs) and Liver X Receptors (LXRs) in the Human Placental Pathophysiology

“…This increase in proinflammatory proteins and cytokines induces uterine contractions. PPAR ligands have been demonstrated to inhibit the secretion of IL6, IL8, and TNF-in amnion and chorion (Lappas et al, 2006), highlighting the role of PPARs in the regulation of the inflammatory response in human gestational tissues and cells (Kniss, 1999;Lappas et al, 2002;Ackerman et al, 2005;Berry et al, 2005). The parathyroid hormone-related protein (presenting a cytokine-like action) is involved in many processes during normal and pathological pregnancies, and is decreased by PPAR stimulation (Lappas & Rice, 2004), which also blocks proinflammatory cytokine release by adiponectin and leptin (Lappas et al, 2005).…”