Prenatal exposure to diazepam: late postnatal teratogenic effect

Area of Science:

• Toxicology
• Developmental Biology
• Immunology

Background:

• Diazepam (DZ) is known to bind to central nervous system and non-neuronal receptors.
• Monocyte receptors are critical for immune system function, including antineoplastic defense.
• Prenatal DZ exposure may suppress the development of brain benzodiazepine receptors.

Purpose of the Study:

• To investigate the long-term effects of prenatal diazepam (DZ) exposure on Sprague-Dawley rat offspring.
• To assess the occurrence of neoplastic and non-neoplastic lesions in DZ-exposed rat progenies.
• To explore potential mechanisms linking DZ exposure to developmental abnormalities and immune system alterations.

Main Methods:

• Pregnant Sprague-Dawley rats were administered daily subcutaneous injections of diazepam (DZ) or vehicle during the last 5 days of gestation.
• Offspring were monitored for up to 20 months for neoplastic and non-neoplastic lesions.
• Plasma immunoglobulin G (IgG) levels, white blood cell counts, and hematocrit values were analyzed.

Main Results:

• DZ-exposed rats showed a significantly higher incidence of neoplasms (13/52), including mammary fibroadenomas and uterine sarcoma, compared to controls (0/44).
• Non-neoplastic lesions, infections, and arteriosclerosis were significantly more prevalent in the DZ-exposed group.
• DZ-exposed rats exhibited lower plasma IgG titres, higher white blood cell counts, and lower hematocrit values.

Conclusions:

• Prenatal diazepam (DZ) exposure is associated with an increased risk of developing neoplasms in rat offspring.
• DZ exposure may impair immune system function, indicated by altered IgG levels and blood cell counts.
• Suppression of peripheral benzodiazepine receptor ontogenesis could explain the teratogenic effects of prenatal DZ exposure.