During gestation, the mother is the main source of thyroid hormones for the foetus. Thus, hypothyroidism during pregnancy and/or preterm birth compromise thyroid hormone supply for the foetus. Maternal hypothyroidism increases risk of preterm birth and both conditions are associated with respiratory distress in infants. Since thyroid hormones are essential for normal brain development, it is plausible that maternal thyroid hormone deficiency plays a role in respiratory disorders related to neurological immaturity in the newborn; however, this hypothesis is yet to be tested. Here, we used methimazole treatment (MMI; 0.05% v/w) from the onset of pregnancy until two weeks postpartum to induce thyroid hormone deficiency in rat pups. At 14-15 days of age, we used plethysmography to measure breathing at rest and in response to hypoxia (12% O2, 20 min) in intact pups. We then used a urethane/chloralose anesthetised preparation to measure cardiorespiratory inhibition induced by laryngeal chemoreflex stimulation. In intact pups, basal breathing did not differ between groups but the breathing frequency response to hypoxia of MMI-treated pups was lower than controls. Following anesthesia, breathing frequency of MMI pups was 60% lower than controls; following laryngeal chemoreflex stimulation, the drop in O2 saturation that was 82% greater in MMI-treated pups than controls. Inactivation of GABAA receptors (bicuculline; 0.5 mg/kg) raised the frequency of anesthetised MMI pups but not control. We conclude that gestational thyroid hormone deficiency interferes with the respiratory and autonomic control systems of the offspring. Thyroid hormone supplementation could alleviate cardiorespiratory disorders in newborn, especially those born preterm.
Keywords: Control of breathing; Development; Hypoxic ventilatory response; Laryngeal chemoreflex; Thyroid hormones.
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