Prenatal exposure to permethrin influences vascular development of fetal brain and adult behavior in mice offspring

Abstract

Pyrethroids are one of the most widely used classes of insecticides and show neurotoxic effects that induce oxidative stress in the neonatal rat brain. However, little is still known about effects of prenatal exposure to permethrin on vascular development in fetal brain, central nervous system development, and adult offspring behaviors. In this study, the effects of prenatal exposure to permethrin on the development of cerebral arteries in fetal brains, neurotransmitter in neonatal brains, and locomotor activities in offspring mice were investigated. Permethrin (0, 2, 10, 50, and 75 mg/kg) was orally administered to pregnant females once on gestation day 10.5. The brains of permethrin-treated fetuses showed altered vascular formation involving shortened lengths of vessels, an increased number of small branches, and, in some cases, insufficient fusion of the anterior communicating arteries in the area of circle of Willis. The prenatal exposure to permethrin altered neocortical and hippocampus thickness in the mid brain and significantly increased norepinephrine and dopamine levels at postnatal day 7 mice. For spontaneous behavior, the standing ability test using a viewing jar and open-field tests showed significant decrease of the standing ability and locomotor activity in male mice at 8 or 12 weeks of age, respectively. The results suggest that prenatal exposure to permethrin may affect insufficient development of the brain through alterations of vascular development.

Developmental neurotoxicity of succeeding generations of insecticides

“…Permethrin, allethrin and bioalletrin are the most frequently studied type I PIs in vitro and in animal models (SM Table 7 and Figure 4). Gestational exposure to type I PIs alters brain vascular formation (Imanishi and others 2013), increases blood-brain barrier permeability (Sinha and others 2004), increases oxidative stress both shortly and long after the end of exposure (Sinha and others 2006), causes functional deficits in the cholinergic muscarinic system (Eriksson and Nordberg 1990), decreases monoamine levels and neocortical and hippocampal thicknesses during postnatal development (Imanishi and others 2013). These effects are accompanied by delayed physical and motor development, decreased locomotor activity, impaired motor coordination (Imanishi and others 2013; Syed and others 2015) and deficient learning and memory (Sinha and others 2006) even at adulthood.…”

Identification of vascular disruptor compounds by analysis in zebrafish embryos and mouse embryonic endothelial cells

“…In addition to genetic status, exposure to certain environmental chemicals adversely affects vascular development of the fetus. Compounds that have vascular disruption activity in vivo include BPA and permethrin in mice [14, 15] and arsenic, cartap, TCCD, and cadmium in zebrafish ([16, 17] and reviewed in McCollum [18]). However, the vast majority of environmental chemicals have not been analyzed for vascular disruption activity, partly due to the lack of complex, mechanistically driven or in vivo high throughput screening (HTS) models.…”

Early‐life exposure to low levels of permethrin exerts impairments in learning and memory with the effects on neuronal and glial population in adult male mice

“…Several studies have suggested that low-level (close to the noobserved-adverse-effect level [NOAEL]) exposure to permethrin at early stages of development can lead to neurological disorders (e.g., thickness of the cortical layer and hippocampal morphological change) and behavioral changes (e.g., decrease of locomotor activity and impairment of long-term memory storage) after maturation in mice and rats (Imanishi et al, 2013;Nasuti et al, 2014), although the levels were not those as low as acceptable daily intake (ADI) levels. In addition, when low-dose permethrin (1:50 LD 50 ; close to the NOAEL) was administered to rats during early life, alterations in heart and in plasma were observed during adult age (Vadhana, Carloni, Nasuti, Fedeli, & Gabbianelli, 2011).…”