Maternal hypothyroidism is an important problem of modern healthcare and is reported to increase the risk of cardiovascular diseases in the offspring later in life. However, it is unclear whether hypothyroidism during pregnancy causes vascular damage in the fetal period. We established the prenatal hypothyroidism rat model and collected the fetuses at the 21th day of gestation (GD21). Thyroid hormone concentrations in maternal and offspring blood serum were assessed by enzyme-linked immunosorbent assay (ELISA). The thoracic aortas of the fetuses were isolated for microvessel functional testing and histochemical stainings. qPCR and Western blot were performed to access mRNA and protein expression. We found that the concentrations of thyroid hormones in the serum of pregnant rats and fetuses were significantly suppressed at GD21. The responses of the fetal thoracic aortas to SNP were significantly attenuated in the PTU group. However, no statistical difference was found between the two groups when treated with either inhibitor (ODQ) or activator (BAY58–2667) of sGC. The production of O₂⁻• in the arterial wall was significantly increased in hypothyroid fetuses. Moreover, the level of NADPH oxidase (NOX) was increased, while superoxide dismutase 2 (SOD2) was down-regulated in the PTU group, ultimately contributing to the increased production of superoxide. Additionally, decreased SNP-mediated vasodilation found in fetal vessels was improved by either NOX inhibitor (Apocynin) or SOD mimic (Tempol). These results indicate that increased oxidative stress is probably the cause of the diminished diastolic effect of exogenous NO in the thoracic artery of prenatal hypothyroidism exposed fetuses.

母亲甲状腺功能减退症是现代医疗保健的一个重要问题，据报道会增加后代患心血管疾病的风险。然而，尚不清楚怀孕期间的甲状腺功能减退是否会导致胎儿期的血管损伤。我们建立了产前甲状腺功能减退症大鼠模型，并在妊娠第21天（GD21）收集胎儿。通过酶联免疫吸附试验（ELISA）评估母体和后代血清中的甲状腺激素浓度。分离胎儿的胸主动脉用于微血管功能测试和组织化学染色。进行 qPCR 和蛋白质印迹以获取 mRNA 和蛋白质表达。我们发现妊娠大鼠和胎儿血清中甲状腺激素的浓度在 GD21 时显着抑制。PTU组胎儿胸主动脉对SNP的反应明显减弱。然而，当用 sGC 的抑制剂 (ODQ) 或激活剂 (BAY58-2667) 治疗时，两组之间没有发现统计学差异。O的生产₂ ^- • 在甲减胎儿的动脉壁明显增加。此外，PTU 组的 NADPH 氧化酶 (NOX) 水平升高，而超氧化物歧化酶 2 (SOD2) 下调，最终导致超氧化物的产生增加。此外，NOX 抑制剂 (Apocynin) 或 SOD 模拟物 (Tempol) 改善了在胎儿血管中发现的 SNP 介导的血管舒张减少。这些结果表明，氧化应激增加可能是产前甲状腺功能减退暴露胎儿胸动脉中外源性 NO 舒张作用减弱的原因。