[Experimental study on DEHP affect the neurodevelopment through interfering with placental thyroid hormones...

Area of Science:

• Toxicology
• Developmental Biology
• Endocrinology

Background:

• Phthalates are common environmental contaminants.
• Di-(2-ethylhexyl) phthalate (DEHP) is linked to developmental toxicity.
• Thyroid hormones (THs) are crucial for neurodevelopment.

Purpose of the Study:

• To investigate the role of THs disruption in DEHP-induced neurodevelopmental toxicity.
• To explore the connection between placental function and neurodevelopmental effects of DEHP.

Main Methods:

• Pregnant mice were administered varying doses of DEHP (0, 10, 50, 200 mg/kg) during critical fetal development periods.
• Thyroid hormone levels (T3, T4, FT3, FT4) in serum and amniotic fluid were measured.
• Placental expression of key TH transporters (MCT8, OATP1C1) and deiodinases (DIO2, DIO3) was analyzed.
• Fetal brain cortical neuron proliferation and migration were assessed using BrdU immunohistochemistry.

Main Results:

• DEHP exposure (50 and 200 mg/kg) significantly decreased amniotic fluid FT3 levels.
• Placental expression of MCT8 and DIO2 decreased in DEHP-exposed groups (50 and 200 mg/kg).
• DEHP (200 mg/kg) reduced BrdU-positive cells in the fetal cerebral cortex, while 50 mg/kg altered cell distribution.

Conclusions:

• DEHP exposure at 50 and 200 mg/kg may impair fetal neurodevelopment.
• Interference with placental thyroid hormone transport is a potential mechanism for DEHP's neurodevelopmental toxicity.
• Further research is needed to fully elucidate the impact of DEHP on neurodevelopmental outcomes.