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بخشی از مقاله انگلیسیعنوان انگلیسی:Alteration of mice cerebral cortex development after prenatal exposure to cypermethrin and deltamethrin~~en~~

Abstract

Pyrethroids, a group of insecticides with high efficiency, low toxicity and wide spectrum, are used for pest control in agriculture. Here, we administered two representative pyrethroids (cypermethrin and deltamethrin) and an equal volume of vehicle (corn oil) to the pregnant ICR mice. This study investigated the effects of cypermethrin and deltamethrin on cerebral cortex development in mice as well as possible mechanisms in proliferation and differentiation. The results showed that histopathologic change did not occurred in the cerebral cortex using Hematoxylin and Eosin staining, however, the observation of fetuses exposed to cypermethrin and deltamethrin revealed reduction of neuronal proliferation, maturation and differentiation. Moreover, cypermethrin/deltamethrin-induced apoptosis of nerve cell was significantly higher in treated groups than that in control group by using flow cytometry, Western blot and TUNEL. It was worth mentioning that the newborns exposed to cypermethrin and deltamethrin did not showed abnormal neuronal distribution. These findings suggested that prenatal cypermethrin and deltamethrin exposure impaired corticogenesis.

Introduction

Chemically synthesized pyrethroids, similar to the natural pyrethroids because of their chemical structure, can affect the function of organs through neurotoxicity (Crago and Schlenk, 2015), endocrine disruption (Jin et al., 2015), abnormal development (Jin et al., 2009) and reproductive toxicity (Wang et al., 2009) in animals. It is now widely used in agricultural pest control and household pest cleanup. The pyrethroids can be classified into type I and type II, and cypermethrin (CP) and deltamethrin (DM) are common pyrethroid II pesticides used worldwide in agriculture, home pest control and disease vector control. In addition, they are considered as an insecticide closely related to human health and food safety (Jin et al., 2015; Singh et al., 2012).

CP and DM accumulate in soil, and traces of them may appear in vegetables, tea, fruits and other foods. CP and DM also have stomach toxicity and brain toxicity (Ncir et al., 2017; Singh et al., 2012). Although long-term exposure to low dose of CP is not enough to cause obvious symptoms of poisoning, the potential damage for reproduction cannot be ignored because of accumulation (Muangphra et al., 2015). CP and DM cause morphometric and structural changes in the genital organs by reducing the number of follicular cells, oocytes and corpora lutea through dose-dependent effects (Marettova et al., 2017; Petr et al., 2013). The previous studies showed that relative toxic potency of six individual pyrethroids for cortical neurons was followed by beta-cyfluthrin, lambda-cyhalothrin, deltamethrin, cypermethrin, bifenthrin and permethrin by disrupting voltage-gated sodium channels and altering cell excitability (Chen et al., 2017; Johnstone et al., 2017; Mohana Krishnan and Prakhya, 2016). In addition, pyrethroids were correlated with carboxylesterase metabolism in liver (Anand et al., 2006), and next generation sequence was used to identify differentially expressed genes for precise molecular mechanisms (Mamidala et al., 2012; Zimmer et al., 2017). Although DM and CP are widely used in human activities, the mechanism of them on cortical neurogenesis remain unclear, so we want to investigate the effect of DM and CP on neuronal progenitor proliferation, cell maturation, neuronal differentiation, apoptosis and neuronal migration in mammalian.

Our results demonstrated that CP/DM exposure inhibited the proliferation of neural precursor cells and neural stem cells, and promoted cell apoptosis in vivo and in vitro. The cell fate decision of newborn neurons was affected by CP and DM, respectively. These findings may be helpful for understanding the neurotoxicity mechanisms of pyrethroids.

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