Influence of nonylphenol exposure on basic growth, development, and thyroid tissue structure in F1 male rats

Abstract

Objective: Environmental endocrine disruptors (EEDs) with a weak ability to mimic estrogen have been associated with thyroid dysfunction. However, little is known about the effect of nonylphenol (NP), a well-known EED, on thyroid structure. The present study evaluates whether gestational and lactational exposure to NP impacts growth and thyroid structure in F1 male rats. Methods: A total of 60 rats were gavaged with NP (25, 50, and 100 mg/kg), estradiol (E2, 30 mg/kg/day), and corn oil alone (vehicle control) from gestational day 6 to postnatal day (PND) 21. Serum thyroid hormones free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone levels were detected by automated chemiluminescence immunoassay analyzer. The NP level in the thyroid was measured using high-performance liquid chromatography. The ultrastructure of follicular epithelial cells was examined using transmission electron microscopy. Histopathology was conducted using hematoxylin and eosin staining. Results: On PND 0, exposure to 50 and 100 mg/kg/day NP led to a significant decrease in the average litter size, litter weight and number of live pups per litter compared to the control group (P < 0.05). Dams exposed to NP during perinatal period demonstrated decreased serum levels of FT3 and FT4 in F1 male rats, when compared to the control group (P < 0.05). The NP level in the control group was 3.39 ± 0.08 ng/mg, while NP levels in the low, middle, and high dose groups ranged from 5.20 to 11.00 ng/mg. Exposure caused a dose-related increase in NP level in the thyroid of male pups (P < 0.01). The thicknesses of the thyroid follicular epithelium were 2.06 ± 0.37 mm in the control group and 3.97 ± 1.61 mm in the high-dose group. The thickness of the thyroid follicular epithelium increased with an increase in treatment dose in a dose-dependent manner (P < 0.05). The sizes of the thyroid follicles were 1,405.53 ± 866.62 mm2 in the control group and 317.49 ± 231.15 mm2 in the high-dose group. With increasing NP dosages, animals showed a decreased size of the thyroid follicle (P < 0.01). Thyroid follicular cells of NP-treated rats showed mildly swollen mitochondria and dilated rough endoplasmic reticulum in the cytoplasm. Conclusion: Nonylphenol can cross the placental barrier and accumulate in the thyroid of F1 male rats. Gestational and lactational exposure to NP in dams impacted both development and growth of pups and damaged the ultrastructure of their thyroid tissue, which may further negatively influence normal thyroid function.