Aguilera Nicole, Salas-Pérez Francisca, Ortíz Macarena, Álvarez Daniela, Echiburú Bárbara, Maliqueo Manuel
Laboratorio de Endocrinología y Metabolismo, Facultad de Medicina Occidente, Universidad de Chile, Santiago, Chile.
Instituto de Ciencias de la Salud, Universidad de O'Higgins, Rancagua, Chile.
Anim Reprod. 2022 Apr 22;19(1):e20210134. doi: 10.1590/1984-3143-AR2021-0134. eCollection 2022.
Rodent models in rats, mice, and guinea pigs have been extremely helpful to gain insight into pregnancy physiology and pathologies-related. Moreover, they have allowed understanding the mechanism that links an adverse intrauterine environment with the origin of adult disease. In this regard, the effects of diverse maternal conditions, such as undernutrition, obesity, hypoxia, and hyperandrogenism on placental function and its long-term consequences for the offspring, have been widely analyzed through rodents models involving dietary manipulations, modifications in environmental oxygen, surgical and pharmacological procedures that reduce uteroplacental blood flow and administrations of exogenous testosterone and dihydrotestosterone (DHT) mimicking maternal androgen excess. Both in human and in rodent models, these interventions induce modifications of placental morphology, transport of glucose, amino acid, and fatty acids, steroid synthesis, and signaling pathways control placental function. These changes are associated with the increase of pro-inflammatory and oxidative stress markers. For its part, offspring exhibit alterations in organs involved in metabolic control such as the hypothalamus, adipose tissue, liver, skeletal muscle, and pancreas altering the intake and preferences for certain foods, the metabolism of glucose and lipid, and hormonal function leading to fat accumulation, insulin resistance, fatty liver, dyslipidemia, and elevated glucose levels. Therefore, the present review discusses the evidence emerging from rodent models that relate maternal nutrition, hypoxia, and androgen exposure to the maternal mechanisms that lead to fetal programming and their metabolic consequences in postnatal life.
大鼠、小鼠和豚鼠的啮齿动物模型对于深入了解妊娠生理学及相关病理状况极为有用。此外，它们还使人们能够理解将不良宫内环境与成人疾病起源联系起来的机制。在这方面，通过啮齿动物模型，广泛分析了各种母体状况（如营养不足、肥胖、缺氧和高雄激素血症）对胎盘功能及其对后代的长期影响，这些模型涉及饮食操控、环境氧气改变、减少子宫胎盘血流量的手术和药理学程序，以及给予外源性睾酮和双氢睾酮（DHT）以模拟母体雄激素过多的情况。在人类和啮齿动物模型中，这些干预都会引起胎盘形态、葡萄糖、氨基酸和脂肪酸转运、类固醇合成以及控制胎盘功能的信号通路的改变。这些变化与促炎和氧化应激标志物的增加有关。就后代而言，其参与代谢控制的器官（如下丘脑、脂肪组织、肝脏、骨骼肌和胰腺）会出现改变，从而改变对某些食物的摄入和偏好、葡萄糖和脂质的代谢以及激素功能，导致脂肪堆积、胰岛素抵抗、脂肪肝、血脂异常和血糖水平升高。因此，本综述讨论了啮齿动物模型中出现的证据，这些证据将母体营养、缺氧和雄激素暴露与导致胎儿编程的母体机制及其对产后生活的代谢后果联系起来。
