Mechanisms of pyrethroid-induced disruption of fetal growth and neurodevelopment

Pyrethroids are a class of insecticides with broad use in household and agricultural insect control. Due to their common use, there is concern regarding their effects on fetal growth and neurodevelopment. To determine how these chemicals may alter development, we conducted a series of experiments to investigate pyrethroid-induced effects in pregnant mice.

Pregnant CD-1 mice were exposed to either the type I pyrethroid permethrin or the type II pyrethroid cypermethrin. Levels of both pyrethroids were low in fetal tissues, suggesting that placental transfer of these chemicals may be minimal. Despite low levels of direct fetal exposure, cypermethrin impaired fetal growth and altered placental structure. No significant effects on placental development or fetal growth were noted for permethrin. Cypermethrin also induced a significant delay in the development of fetal brain immune cells, while minimal effects were observed for permethrin.

We next investigated whether cypermethrin-induced effects on the fetus in utero could be altered by co-exposure to maternal stress. Pregnant CD-1 mice were exposed to cypermethrin, alone and in combination with maternal restraint stress. Cypermethrin significantly altered development of GABAergic neurons in the fetal brain, cells that are critical for normal brain function. Interestingly, co-exposure to cypermethrin and stress resulted in higher levels of cypermethrin in maternal blood and additive effects on placental function and fetal neurodevelopment.

Overall, these studies suggest that pyrethroids affect the placenta and the developing brain in utero, with enhanced effects observed in stressed animals. We also demonstrate that these effects are of particular concern for type II pyrethroids such as cypermethrin.