PARENT SESSION

(60) DECLINE IN 15-HYDROXY PROSTAGLANDIN DEHYDROGENASE ACTIVITY IN HUMAN PLACENTAL AND CHORIONIC CELLS EXPOSED TO POLYCHLORINATED BIPHENYLS.

Thiex, Natalie ¹, Loch Caruso, Rita¹, ¹ University of Michigan, Ann Arbor, MI

ABSTRACT- 15-hydroxy prostaglandin dehydrogenase (PGDH) is a NAD+ dependent enzyme that metabolizes prostaglandins to inactive metabolites. Prostaglandin E₂ (PGE₂) and prostaglandin F₂ (PGF₂) are uterotonic hormones that cause contraction of the uterus at the time of parturition. Prior to parturition, PGE₂ and PGF₂ made in the amnion are catabolized to inactive metabolites by PGDH in the chorion. Disruption of PGDH activity before parturition may result in preterm exposure of myometrium to uterotonic prostaglandins. Polychlorinated biphenyls (PCBs) are lipophilic toxicants ubiquitous in the environment, and they have historically been detected in extracted lipids of the uterus, placenta and fetal membranes of women. PCBs have been associated with shortened gestation length in occupationally exposed or sport fish eating populations. The objective of this research was to determine the effect of PCB exposure on PGDH activity in chorion and placental cells cultured in vitro. Primary cells were isolated from chorion and placentae collected from full term non-laboring Cesarean section deliveries. After three days in culture, PCBs and PCB metabolites (hydroxylated PCBs) were administered to the cells. PGDH activity was determined by measuring conversion of exogenous PGF₂ to its 15-keto metabolite (PGFM) after toxicant exposure. PGFM concentrations were measured using an enzyme immunoassay. Ortho substituted PCB congeners 138 and 153 and hydroxylated PCBs (2′,4′,6′-trichloro-4-biphenylol and 2′,3′,4′,5′-tetrachlo-4-biphenylol) decreased conversion of PGF₂ to PGFM in placenta and chorion cells in a concentration-dependent manner (10-50 M). These results show that PCBs alter normal prostaglandin metabolism in cells from gestational tissues in vitro. Similar effects may occur in vivo due to localization of PCBs to sites of prostaglandin synthesis and metabolism whereby excess prostaglandins could access the myometrium leading to preterm labor.

KEY WORDS: prostaglandin dehydrogenase, polychlorinated biphenyl, placenta, parturition