Trichloroethylene exposure in mid-pregnancy decreased fetal weight and increased placental markers of oxidative stress in rats

Abstract

Although epidemiology studies have associated maternal trichloroethylene (TCE) exposure with decreased birth weight and preterm birth, mechanistic explanations for these associations are currently lacking. We hypothesized that TCE targets the placenta with adverse consequences for pregnancy outcomes. Pregnant Wistar rats were exposed orally to vehicle or 480 mg TCE/kg body weight from gestational days (gd) 6-16, and tissues were collected on gd 16. Exposure to TCE significantly decreased average fetal weight without reducing maternal weight. In placenta, TCE significantly increased 8-hydroxy-deoxyguanosine, global 5-hydroxymethylcytosine, and mRNA expression of Tet3, which codes for an enzyme involved in 5-hydroxymethylcytosine formation. Furthermore, glutathione S-transferase activity and immunohistochemical staining were increased in placentas of TCE-exposed rats. The present study provides the first evidence that TCE increases markers of oxidative stress in placenta in a fetal growth restriction rat model, providing new insight into the placenta as a potentially relevant target for TCE-induced adverse pregnancy outcomes.

Keywords: 5-Hydroxymethylcytosine; 8-Hydroxy-deoxyguanosine; Fetal growth restriction; Glutathione S-transferase; Oxidative stress; Trichloroethylene; Wistar rats.