Paz Adolfo A, Jiménez Tamara A, Ibarra-Gonzalez Julieta, Astudillo-Maya Cristian, Beñaldo Felipe A, Figueroa Esteban G, Llanos Aníbal J, Gonzalez-Candia Alejandro, Herrera Emilio A
Laboratorio de Función y Reactividad Vascular, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Instituto de Ciencias de la Salud, Universidad de O'Higgins, Rancagua, Chile.
Life Sci. 2025 Jan 15;361:123282. doi: 10.1016/j.lfs.2024.123282. Epub 2024 Nov 29.
Gestational hypoxia (GH) has been implicated in the developmental programming of cardiovascular diseases (CVDs) in the offspring, with most studies focusing on males, conversely, the effects on female cardiovascular health remain understudied. We aimed to investigate the impact of GH on the cardiovascular system of female guinea pig offspring from the early postnatal period to adulthood.
Pregnant guinea pigs were subjected to normoxic or hypoxic conditions from gestational day 30 until delivery (∼70 days). Female offspring were monitored with biometric parameters and peripheral vascular function (ultrasound) from birth to one year old. In addition, we assessed cardiovascular structure, oxidative stress, inflammatory state (IHC, qPCR, and immunoblot assays), and thoracic aorta reactivity (wire-myography) at one year of age.
GH increased heart rate and peripheral pulsatility index. At one year old, GH-exposed females exhibited cardiac remodeling, characterized by increased left ventricular luminal area and coronary artery muscle occupation. Furthermore, GH increased aortic vascular wall, intima-media thickness and contractile capacity. This was accompanied by reduced endothelium-dependent vasodilation and enhanced oxidative stress. Additionally, GH increased collagen deposition and oxidative stress in the right ventricle, accompanied by reduced antioxidant enzymes expression and reduced inflammatory mediator levels.
GH exerts long-lasting effects on the cardiovascular health of female guinea pig offspring, contributing to cardiac remodeling, vascular dysfunction, oxidative stress, and inflammatory changes. These findings highlight the importance of GH as a risk factor for developing CVDs in female offspring and emphasize the need for sex-specific interventions to mitigate adverse long-term gestational effects.
妊娠期缺氧（GH）与后代心血管疾病（CVD）的发育编程有关，大多数研究集中在雄性，相反，对雌性心血管健康的影响仍未得到充分研究。我们旨在研究妊娠期缺氧对雌性豚鼠后代从出生后早期到成年期心血管系统的影响。
怀孕的豚鼠在妊娠第30天至分娩（约70天）期间处于常氧或缺氧条件下。对雌性后代从出生到一岁进行生物特征参数和外周血管功能（超声）监测。此外，我们在一岁时评估了心血管结构、氧化应激、炎症状态（免疫组化、定量聚合酶链反应和免疫印迹分析）以及胸主动脉反应性（线肌张力测定法）。
妊娠期缺氧增加了心率和外周搏动指数。一岁时，暴露于妊娠期缺氧的雌性表现出心脏重塑，其特征是左心室腔面积增加和冠状动脉肌肉占有率增加。此外，妊娠期缺氧增加了主动脉血管壁、内膜中层厚度和收缩能力。这伴随着内皮依赖性血管舒张功能降低和氧化应激增强。此外，妊娠期缺氧增加了右心室的胶原蛋白沉积和氧化应激，同时抗氧化酶表达减少，炎症介质水平降低。
妊娠期缺氧对雌性豚鼠后代的心血管健康产生长期影响，导致心脏重塑、血管功能障碍、氧化应激和炎症变化。这些发现突出了妊娠期缺氧作为雌性后代患心血管疾病风险因素的重要性，并强调需要进行针对性别的干预措施以减轻妊娠期不良长期影响。
