Gestational 1-nitropyrene exposure causes fetal growth restriction through disturbing placental vascularity and proliferation

1-Nitropyrene (1-NP) is a widely distributed pollutant in the environment and is best known for its mutagenicity and carcinogenicity. In this study, we evaluated the effects of 1-NP exposure in different gestational stages on the pregnant outcomes. Pregnant mice were administered with 1-NP by gavage daily in early (GD1-GD6), middle (GD7-GD12) or late pregnancy (GD13-GD17), respectively. We found that gestational 1-NP exposure had no effect on implantation sites per litter, preterm delivery and fetal death. Interestingly, mice exposed to 1-NP in late pregnancy showed a significant reduction in fetal weight and crown-rump length. Correspondingly, placental weight and diameter were markedly reduced in dams exposed to 1-NP in late pregnancy. Additional experiment showed maternal 1-NP exposure in late pregnancy reduced blood sinusoid area of placental labyrinthine region in a dose-dependent manner. Although gestational 1-NP exposure had little effect on placental cell apoptosis, as determined by the TUNEL assay, the rate of Ki67-positive cell, a marker of cell proliferation, was reduced in placental labyrinthine region of mice exposed to 1-NP in late pregnancy. These findings provide evidence that gestational 1-NP exposure induces fetal growth restriction in a stage-dependent manner. Placenta is a toxic target in the process of 1-NP-induced fetal growth restriction. (C) 2018 Elsevier Ltd. All rights reserved.