PPAR Action in Human Placental Development and Pregnancy and Its Complications

Abstract

During pregnancy crucial anatomic, physiologic, and metabolic changes challenge the mother and the fetus. The placenta is a remarkable organ that allows the mother and the fetus to adapt to the new metabolic, immunologic, and angiogenic environment imposed by gestation. One of the physiologic systems that appears to have evolved to sustain this metabolic regulation is mediated by peroxisome proliferator-activated receptors (PPARs). In clinical pregnancy-specific disorders, including preeclampsia, gestational diabetes, and intrauterine growth restriction, aberrant regulation of components of the PPAR system parallels dysregulation of metabolism, inflammation and angiogenesis. This review summarizes current knowledge on the role of PPARs in regulating human trophoblast invasion, early placental development, and also in the physiology of clinical pregnancy and its complications. As increasingly indicated in the literature, pregnancy disorders, such as preeclampsia and gestational diabetes, represent potential targets for treatment with PPAR ligands. With the advent of more specific PPAR agonists that exhibit efficacy in ameliorating metabolic, inflammatory, and angiogenic disturbances, further studies of their application in pregnancy-related diseases are warranted.

Role of lipids on elongation of the preimplantation conceptus in ruminants

“…3); third, level of expression of PPARG was correlated highly with the level of expression of several other genes known to influence conceptus development or lipid metabolism (Fig. 2B, Wieser et al 2008).…”

Preterm and infection-driven preterm labor: the role of peroxisome proliferator-activated receptors and retinoid X receptor

“…The causes of PROM are numerous, and in part are caused by apoptosis and inflammatory cytokines (Fortunato & Menon 2001, Menon & Fortunato 2004, Reti et al 2007. Increased expression or activation of PPARs have been associated with apoptosis (Keelan et al 2001, Yang & Frucht 2001, Wieser et al 2008) and pro-inflammatory cytokines (Ackerman et al 2005).…”

“…We and others have presented data implicating PPARs in the inflammatory events that contribute to normal labor at term (Lim & Dey 2000, Lappas et al 2002b, Berry et al 2003, Dunn-Albanese et al 2004, Ackerman et al 2005, Lindstrom & Bennett 2005, Froment et al 2006, Schaiff et al 2006, Fournier et al 2007, Holdsworth-Carson et al 2009). PPARs exhibit anti-inflammatory properties (Jiang et al 1998, Ricote et al 1998, Delerive et al 2001, Daynes & Jones 2002, Lappas et al 2002b, Kielian et al 2008, Perez et al 2008 and are hypothesized to promote pregnancy quiescence and initiate labor (Dunn-Albanese et al 2004, Froment et al 2006, Schaiff et al 2006, Wieser et al 2008. There are three isoforms of PPAR nuclear receptors (a (PPARA), d (PPARD), and g (PPARG)) and they act as liganddependent transcription factors (Issemann & Green 1990, Dreyer et al 1992.…”

“…Research has inferred a role for PPAR in preterm labor (Schaiff et al 2006, Borel et al 2008, Wieser et al 2008) and carriers of a PPARG genetic polymorphism have been associated with being born prematurely (Meirhaeghe et al 2007). PPAR-associated inflammatory mediator suppression suggests that a breakdown in PPAR expression or activity may be apparent during periods of preterm intra-amniotic infection, as seen in non-gestational tissue infections (Kielian et al 2008, Perez et al 2008.…”

“…PPAR-associated inflammatory mediator suppression suggests that a breakdown in PPAR expression or activity may be apparent during periods of preterm intra-amniotic infection, as seen in non-gestational tissue infections (Kielian et al 2008, Perez et al 2008. While some groups have investigated PPAR expression in first (Tarrade et al 2001, Capparuccia et al 2002, Rodie et al 2005 and second trimester placenta (Waite et al 2000, Rodie et al 2005 and serum samples throughout the course of pregnancy (Wieser et al 2008), data are lacking regarding the expression and activity of PPAR isoforms in association with preterm delivery, with and without infection. The aim of this study was to compare the expression and DNA binding activity patterns of PPAR isoforms and the expression of RXRA in human gestational tissues from term and preterm vaginal deliveries, and to determine the effect of infectionassociated preterm delivery on PPAR isoforms and RXRA expression.…”