Effects of perinatal di (2-ethylhexyl) phthalate exposure on thyroid function in rat offspring.

Di (2-ethylhexyl) phthalate (DEHP) is a commonly used plasticizer in industry and displays the characteristics of an endocrine disruptor. Disorders of the maternal thyroid hormone (TH) during pregnancy can cause adverse effects on the fetus. We investigated the effects and possible mechanism of perinatal DEHP exposure on the thyroid function of pups. Pregnant female Wistar rats were randomly divided into four groups and received doses of DEHP of 0, 30, 300, 750 mg/kg/day by gavage at from gestational day (GD) 0 to postnatal day (PN) 21. The concentration of serum THs and the ultrastructure of thyroid follicular cells in the offspring were examined. Related protein level and gene expression of thyroid proteins in pups were analyzed by western blotting and real-time PCR. We found that DEHP significantly reduced total thyroxine (TT4 ) and increased thyroid stimulating hormone (TSH) in pups, while total triiodothyronine (TT3 ) showed no change. Thyroid follicular cells ultrastructure was damaged in DEHP exposed pups as viewed by electron microscopy. Furthermore, exposure to DEHP significantly increased protein and mRNA levels of thyroid transcription factor 1 (TTF-1), paired box 8 (PAX8), sodium iodide symporter (NIS) and thyroid peroxidase (TPO) in pups. In addition, levels of deiodinases of pups were also affected. These findings indicated that DEHP can disrupt thyroid function by damaging thyroid follicles and affecting TTF-1, PAX8, NIS, TPO and the deiodinase protein family.