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

Am J Pathol. 2015 Jul;185(7):1981-90. doi: 10.1016/j.ajpath.2015.03.021.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cells, Cultured
  • Chorion / enzymology
  • Chorion / metabolism*
  • Female
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Hydroxyprostaglandin Dehydrogenases / genetics
  • Hydroxyprostaglandin Dehydrogenases / metabolism*
  • Infant, Newborn
  • Male
  • PPAR alpha / genetics
  • PPAR alpha / metabolism*
  • Peroxisome Proliferator-Activated Receptors / genetics
  • Peroxisome Proliferator-Activated Receptors / metabolism*
  • Pregnancy
  • Premature Birth
  • Prostaglandins / metabolism
  • Protein Isoforms
  • RNA, Messenger / genetics
  • Term Birth
  • Trophoblasts / metabolism

Substances

  • PPAR alpha
  • Peroxisome Proliferator-Activated Receptors
  • Prostaglandins
  • Protein Isoforms
  • RNA, Messenger
  • Hydroxyprostaglandin Dehydrogenases
  • 15-hydroxyprostaglandin dehydrogenase