Gestational doxorubicin alters fetal thyroid-brain axis

Area of Science:

• Neuroendocrinology
• Developmental toxicology
• Neurobiology

Background:

• Chemotherapy administration during pregnancy poses risks to fetal brain development.
• Doxorubicin (DOX) crosses the placenta, raising concerns about its impact on the developing neuroendocrine system.

Purpose of the Study:

• To investigate the effects of maternal doxorubicin (DOX) administration on the fetal neuroendocrine system and brain development in rats.
• To assess DOX-induced alterations in thyroid hormones, growth hormone, nucleotides, and ATPase activities in the fetal brain.

Main Methods:

• Pregnant rats received doxorubicin (DOX) throughout gestation.
• Maternal and fetal thyroid hormone levels, fetal growth hormone, nucleotides, and ATPase activities were measured at gestation days 15 and 20.
• Cerebrum and cerebellum were analyzed for biochemical markers of brain development and function.

Main Results:

• Maternal DOX administration induced fetal hypothyroidism, characterized by decreased T4, T3, and increased TSH levels.
• Fetal growth hormone levels decreased significantly in the DOX-exposed group.
• DOX exposure reduced fetal brain nucleotide levels and ATPase activities, while altering adenylate energy charge.

Conclusions:

• Doxorubicin (DOX) acts as a neuroendocrine disruptor during pregnancy, leading to fetal hypothyroidism and impaired brain energy metabolism.
• These neuroendocrine and energetic dysfunctions may negatively impact nerve transmission and overall fetal brain development.
• The study highlights the potential risks of chemotherapy during pregnancy for neurodevelopmental outcomes.