Thyroid hormones (THs) are essential for foetal brain development. Because the gestating mother is the main source of THs to the foetus, maternal hypothyroidism and/or premature birth compromise neurological outcomes in the offspring. Respiratory instability and recurrent apneas due to immaturity of the respiratory control network are major causes of morbidity in infants. Inadequate TH supply may be sufficient to delay perinatal maturation of the respiratory control system; however, this hypothesis remains untested. To address this issue, maternal hypothyroidism was induced by adding methimazole (MMI; 0.02% w/v) to the drinking water of pregnant dams from conception to postpartum day 4 (P4). The effect of TH supplementation on respiratory function was tested by injecting levothyroxine (L-T4) in newborns at P1. Respiratory function was assessed by plethysmography (in vivo) and recording of phrenic output from medullary preparations (in vitro). By comparison with controls, TH deficiency increased the frequency of apneas and decreased basal ventilation in vivo and prevented the age-dependent increase in phrenic burst frequency normally observed in vitro. The effects of TH deficiency on GABAergic modulation of respiratory activity were measured by bath application of muscimol (GABA_A agonist) or bicuculline (GABA_A antagonist). The phrenic burst frequency responses to GABAergic agents were consistently greater in preparations from TH deficient pups. L-T4 supplementation reversed part of the respiratory anomalies related to MMI treatment in vitro. We conclude that TH deficiency during the perinatal period is sufficient to delay maturation of the respiratory control network development. Excessive GABAergic inhibition may contribute to this effect.

甲状腺激素 (THs) 对胎儿大脑发育至关重要。由于妊娠母亲是胎儿 THs 的主要来源，因此母体甲状腺功能减退和/或早产会损害后代的神经系统结果。由于呼吸控制网络不成熟导致呼吸不稳定和反复呼吸暂停是婴儿发病的主要原因。TH 供应不足可能足以延迟呼吸控制系统的围产期成熟；然而，这一假设仍未得到检验。为了解决这个问题，通过添加甲巯咪唑（MMI; 0.02% w / v) 从受孕到产后第 4 天 (P4) 的怀孕母猪的饮用水。通过在 P1 时在新生儿中注射左旋甲状腺素 (L-T4) 来测试 TH 补充剂对呼吸功能的影响。呼吸功能是通过体积描记法（评估在体内），并从髓制剂膈输出的记录（在体外）。与对照组相比，TH 缺乏增加了呼吸暂停的频率并降低了体内的基础通气量，并阻止了通常在体外观察到的膈肌爆发频率的年龄依赖性增加。TH 缺乏对呼吸活动的 GABA 能调节的影响通过沐浴应用 muscimol（GABA _A激动剂）或荷包牡丹碱（GABA_一拮抗剂）。在来自 TH 缺陷幼崽的制剂中，对 GABA 能药物的膈突发频率反应始终较大。L-T4 补充剂在体外逆转了与 MMI 治疗相关的部分呼吸异常。我们得出结论，围产期 TH 缺乏足以延迟呼吸控制网络发育的成熟。过度的 GABA 能抑制可能导致这种效果。