Propylthiouracil is teratogenic in murine embryos

Area of Science:

• Developmental toxicology
• Pharmacology
• Reproductive medicine

Background:

• Hyperthyroidism in pregnancy necessitates antithyroid drug (ATD) treatment.
• Propylthiouracil (PTU) is the preferred ATD in early pregnancy.
• Formal studies on ATD teratogenic effects are lacking.

Purpose of the Study:

• To investigate the teratogenic effects of PTU and methimazole (MMI) during mouse embryogenesis.
• To assess the impact of ATD exposure on embryonic development and identify potential risks.

Main Methods:

• Mice dams were treated with PTU, MMI, or vehicle during critical embryonic periods (E7.5-9.5 or E3.5-7.5).
• Embryos were analyzed for gross malformations, cardiac abnormalities, and gene expression changes (RNA microarray).
• Histological and micro-CT analyses were performed at embryonic days E10.5 and E18.5.

Main Results:

• PTU exposure from E7.5-9.5 led to neural tube and cardiac defects at E10.5.
• PTU-exposed embryos showed significantly higher rates of cranial neural tube defects and pericardial blood.
• PTU exposure was associated with fetal loss and disrupted gene pathways related to cytoskeleton remodeling.

Conclusions:

• Propylthiouracil (PTU) demonstrates teratogenic potential during mouse embryogenesis.
• PTU exposure is linked to neural tube closure delays and cardiac abnormalities.
• Methimazole (MMI) exhibited fewer structural defects, suggesting a potentially safer profile in early pregnancy.