Expression of 15-Hydroxyprostaglandin Dehydrogenase in Human Chorion Is Associated with Peroxisome Proliferator-Activated Receptor Isoform Expression in Term Labor

Abstract

Chorionic NAD-dependent 15-hydroxy prostaglandin dehydrogenase (PGDH) plays a pivotal role in controlling the amount of prostaglandins in the uterus. Peroxisome proliferator-activated receptors (PPARs) are implicated to be involved in parturition. In this study, we investigated whether PPARs are involved in control of PGDH expression in chorion. The chorionic tissues were collected from the following groups of the women with singleton pregnancy: term no labor (TNL), term labor (TL) and preterm labor (PTL). Chorionic trophoblasts were isolated and cultured in vitro. Immunocytochemistry analysis showed that PPARα, PPARβ, and PPARγ were localized to trophoblasts in chorion. The protein levels of PGDH, PPARβ, and PPARγ were localized to trophoblasts in chorion. The protein levels of PPARα, PPARβ, and PPARγ were reduced in TL tissues compared to that of TNL group. PPARα, PPARβ, and PPARγ expression correlated to PGDH in TNL tissues, whereas only PPARγ expression correlated to PGDH in TL chorion tissues. PGDH expression was decreased in PTL tissues compared with TL group, whereas the expression of PPARs was not significantly different between TL and PTL groups. The agonists of three PPARs dose-dependently stimulated PGDH activity, mRNA, and protein expression in cultured chorionic cells. PPARs did not affect the stability of PGDH mRNA but stimulated the transcriptional activity of HPGD gene. Our results suggest that PPARs play pivotal roles in maintenance of PGDH expression in chorion during human pregnancy.

Proteomic Study of Fetal Membrane: Inflammation-Triggered Proteolysis of Extracellular Matrix May Present a Pathogenic Pathway for Spontaneous Preterm Birth

“…Numerous studies indicated that placental intrauterine infection was strongly associated with sPTL or PPROM (Salafia et al, 1991;Helmig et al, 2002;Morgan, 2016;Pugni et al, 2016;Chisholm et al, 2018). A study in humans demonstrated that HPGD expression in preterm-labor placenta tissues was decreased in comparison with a full-term labor group (He et al, 2015). HPGD is a member of the short-chain non-metalloenzyme alcohol dehydrogenases protein family and is responsible for the degradation of prostaglandins, hormones that modulate the inflammatory response (Aoki and Narumiya, 2012;Seo and Oh, 2017).…”

Reduced Expression of Hydrogen Sulfide–Generating Enzymes Down-Regulates 15-Hydroxyprostaglandin Dehydrogenase in Chorion during Term and Preterm Labor

“…29 Our previous studies have shown that corticotropinreleasing hormone and peroxisome proliferator-activated receptors play pivotal roles in the regulation of PGDH in the chorion during pregnancy. 23,30 Moreover, we have also demonstrated that reduced PGDH expression is associated AeC: The effect of NaHS on PGDH mRNA (A) and protein (B) expression as well as activity (C). Cells were treated with an increasing concentration of NaHS (10 À5 to 10 À4 mol/L) for 24 hours.…”

“…with decreased expression of peroxisome proliferatoractivated receptor-g and increased expression of glucocorticoid receptor and progesterone receptor A. 30,31 Herein, hydrogen sulfide produced locally increased PGDH expression in the chorion, and PGDH expression correlated with the expression level of hydrogen sulfideegenerating enzymes in the chorion. Taken together, this suggests that the PGDH expression level is controlled by a molecular network within the chorion.…”

“…Moreover, our previous studies have shown that PGDH expression is modulated by various factors. 30,31 Thus, the regulatory mechanisms responsible for PGDH expression remain to be further elucidated.…”

Research Advances in the Correlation between Peroxisome Proliferator-Activated Receptor-γ and Digestive Cancers

“…Natural ligands include all kinds of unsaturated fatty acids and their metabolic derivatives, such as linoleic acid, linolenic acid, and eicosapentaenoic acid. Certain prostaglandins and their metabolic derivatives also belong to natural ligands, and currently 15-deoxygenated prostaglandin is known to possess the strongest metabolic activity [ 12 ]. On the other hand, the synthetic ligand is mainly composed of thiazolidinedione compounds (troglitazone, rosiglitazone, pioglitazone, etc.).…”