Critical time window of fenvalerate-induced fetal intrauterine growth restriction in mice

Highlight：妊娠晚期是氰戊菊酯诱发胎儿宫内生长受限的关键时间窗。加强孕期尤其是孕晚期避免接触环境有害因素是预防胎儿宫内生长受限的重要措施。

Abstract

Fenvalerate (FEN), a representative type II pyrethroid, is a widely used pyrethroid insecticide and a potential environmental contaminant. Several studies demonstrated that gestational FEN exposure induced intrauterine growth restriction (IUGR). However, the critical time window of FEN-induced fetal IUGR remains obscure. The present study aimed to identify the critical window of FEN-induced fetal IUGR. Pregnant mice were administered corn oil or FEN (20mg/kg) by gavage daily at the early gestational stage (GD0-GD6), middle gestational stage (GD7-GD12) or late gestational stage (GD13-GD17). The results showed that the rates of fetal IUGR were markedly increased only in the mice exposed to FEN on GD13-GD17 but not in the mice exposed to FEN on GD7- GD12 or GD0-GD6. Further analysis showed that the blood sinusoid area in the placental labyrinth layer was reduced in the mice exposed to FEN on GD13-GD17. In addition, CD34+ microvessel density in the labyrinthine region was decreased in the male and female fetuses whose mothers were exposed to FEN on GD13-GD17. Mechanistic analysis found that the glutathione level was decreased in the FEN-exposed placentas. In contrast, the levels of 3-nitrotyrosine and malondialdehyde, two oxidative stress markers, were increased in FEN-exposed placentas. Heme oxygenase-1, inducible nitric oxide synthase, catalase and peroxiredoxin-3, which are antioxidant enzymes, were upregulated in the FEN-exposed placentas. The present study suggests that the late gestational stage is a critical time window of FEN-induced fetal IUGR. Placental oxidative stress may be, at least partially, involved in the process of FEN-induced placental damage and fetal IUGR.

Ce Guo, Yang Yang, Meng-Xing Shi, Bo Wang, Ji-Jie Liu, De-Xiang Xu, Xiu-Hong Meng. Critical time window of fenvalerate-induced fetal intrauterine growth restriction in mice. Ecotoxicol Environ Saf, 2019, 172: 186-193.