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 (20â¯mg/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.
Subject(s)
Fetal Growth Retardation/chemically induced , Insecticides/toxicity , Maternal Exposure , Nitriles/toxicity , Placenta/drug effects , Pyrethrins/toxicity , Animals , Antioxidants/metabolism , Female , Fetus/drug effects , Gestational Age , Male , Mice , Microvessels/drug effects , Oxidative Stress/drug effects , Placenta/metabolism , Pregnancy , Time FactorsABSTRACT
Although use of fenvalerate has increased dramatically over the past decade, little is known about their potential adverse effects on growth and development. The purpose of this study was to examine the effects of maternal fenvalerate exposure during pregnancy on growth and neurobehavioral development in the offspring. Pregnant mice were orally administered to fenvalerate (0.2, 2.0, and 20 mg/kg) daily throughout pregnancy. The tests of growth and neurobehavioral development were performed during lactation period. A series of neurobehavioral tasks were carried out from lactation to puberty. Anxiety-related behaviors were evaluated by open-field and elevated plus maze. Morris Water Maze was used to assess spatial learning and memory ability. Results showed that maternal fenvalerate exposure during pregnancy markedly delayed growth development of neonatal offspring during lactation. In addition, anxiety-like behaviors were increased in fenvalerate-exposed male offspring. Moreover, spatial learning and memory was severely impaired in female offspring. Taken together, maternal fenvalerate exposure during pregnancy delayed growth and neurobehavioral development in a gender-dependent manner. Additional study is required to explore the underlying mechanism through which maternal fenvalerate exposure during pregnancy induces impairment of growth and neurobehavioral development.
Subject(s)
Growth/drug effects , Maternal Exposure/adverse effects , Nitriles/adverse effects , Prenatal Exposure Delayed Effects/psychology , Pyrethrins/adverse effects , Spatial Learning/drug effects , Spatial Memory/drug effects , Animals , Behavior, Animal/drug effects , Disease Models, Animal , Female , Lactation , Male , Mice , Pregnancy , Sex CharacteristicsABSTRACT
Fenvalerate is an environmental endocrine disruptor that disrupts testosterone and estradiol synthesis. Nevertheless, whether fenvalerate disturbs placental TR signaling remains unclear. The aim of this study was to investigate whether maternal fenvalerate exposure causes fetal intrauterine growth restriction (IUGR) and to explore the role of placental thyroid hormone receptor (TR) signaling. Pregnant mice except controls were orally administered to fenvalerate (0.2, 2.0, or 20 mg/kg) daily throughout pregnancy. As expected, fetal weight was lowered in dams that were administered with 20.0 mg/kg of fenvalerate. Moreover, the rate of IUGR was elevated not only in male fetuses but also in female fetuses of dams exposed to 20.0 mg/kg of fenvalerate. Histopathology showed that the internal space of blood vessels in the labyrinth layer was smaller in placentas of mice exposed to fenvalerate. Mechanistic study found no significant difference on TT4 level in maternal serum, although TT3 level in maternal serum was slightly reduced in dams exposed to 2.0 mg/kg of fenvalerate. Interestingly, placental TRα1 and TRß1 mRNAs were reduced in mice exposed to fenvalerate. Moreover, nuclear translocation of placental TRß1 was suppressed in fenvalerate-exposed mice. Further analysis showed that placental Vegfα and Igf2, several target genes of TR signaling, were down-regulated in fenvalerate-exposed mice. In addition, mRNA level of placental CD36, Snat1, and Snat2, 3 nutrient transporters, were reduced in fenvalerate-exposed mice. These results suggest that maternal fenvalerate exposure induces fetal IUGR through disrupting placental TR signaling. These results provide a novel mechanistic explanation for fenvalerate-induced fetal IUGR.
