Skeletal development following heat exposure in the rat

Area of Science:

• Developmental biology
• Toxicology
• Teratology

Background:

• Heat stress during pregnancy is a potential risk factor for adverse developmental outcomes.
• Understanding the precise temperature thresholds and timing for teratogenic effects is crucial for risk assessment.

Purpose of the Study:

• To determine the temperature-response relationship for heat-induced skeletal and other defects in rat pups.
• To investigate the effects of maternal heat exposure on gestation day 10.

Main Methods:

• Pregnant rats were exposed to controlled heat stress at gestation day 10.
• Core body temperature was monitored using rectal probes and telemetric procedures.
• Offspring were examined for malformations at postnatal day 3, with a second experiment using anesthetized dams for reduced stress.

Main Results:

• Maternal core body temperatures of 41-41.9°C resulted in >90% malformed pups and a 25% reduction in live pups.
• Temperatures of 42°C or higher were lethal to maternal rats.
• Anesthetized dams exposed to 42-42.5°C showed similar pup defects, indicating stress reduction did not alter outcomes significantly.
• Skeletal defects primarily affected the axial skeleton, including ribs and vertebrae, correlating with somite development stage.

Conclusions:

• Maternal heat exposure at gestation day 10 is a potent teratogen, inducing significant skeletal abnormalities in rat offspring.
• A clear temperature threshold exists for teratogenic effects, with temperatures >41°C posing a high risk.
• The timing of heat exposure relative to embryonic development, specifically somite formation, influences the type and severity of defects.