Abstract:
Objective: To investigate the effects of clothianidin(CLO) exposure on the thyroid function of maternal rats and the early neurodevelopment of their offspring by establishing a CLO exposure model in SpragueDawley(SD) rats during pregnancy and lactation.
Methods: Rats with confirmed pregnancy were randomly divided into 4 groups: control group, low-dose group(20 mg·kg
-1·d
-1 CLO), medium-dose group(65 mg·kg
-1·d
-1 CLO), and high-dose group(130 mg·kg
-1·d
-1 CLO), with 10 rats per group. From the day of pregnancy to postnatal day 21, the rats were administered the test substance via oral gavage once daily at a volume of 5 mL/kg body mass, and their body mass were monitored. For the offspring rats, early neurobehavioral reflex tests including surface righting reflex, negative geotaxis, and cliff avoidance reflex, were conducted on postnatal days 7 and 9. Morphological changes of the thyroid tissue in maternal rats were observed via hematoxylin-eosin(HE) staining. Chemiluminescence immunoassay was used to detect the levels of five serum thyroid function indices in maternal rats, including thyroid-stimulating hormone(TSH), total triiodothyronine(TT3), free triiodothyronine(FT3), total tetraiodothyronine(TT4), and free tetraiodothyronine(FT4).
Results: Compared with the control group, the maternal rats in the high-dose group showed a significant decrease in the mass gain rate during pregnancy(
P<0.05), while the liver organ coefficients of maternal rats in the medium-dose and high-dose groups were significantly increased(
P<0.05). HE staining revealed that the thyroid follicular structure was impaired and intrafollicular colloid content was reduced in the maternal rats of the medium-dose and high-dose groups. In terms of maternal serum thyroid function indices, the levels of TSH, TT4, and FT4 in the medium-dose and high-dose groups were significantly lower than those in the control group(
P<0.05), while no significant differences were observed in the levels of TT3 and FT3 between the dose groups and the control group(
P>0.05). For the offspring rats, the body mass of offspring in the medium-dose and high-dose groups was significantly lower than those in the control group(
P<0.001). The reflex latencies of surface righting reflex and cliff avoidance reflex in the offspring of the high-dose group, as well as the reflex latency of negative geotaxis in all dose groups, were significantly prolonged compared with the control group(
P<0.05).
Conclusion: Exposure to CLO during pregnancy and lactation may not only induce damage to maternal organs but also disrupt the homeostasis of maternal thyroid hormone levels, thereby exerting adverse effects on the early physical development and neurodevelopment of their offspring.