Gestational hypoxia elicits long-term cardiovascular dysfunction in female guinea pigs

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BackgroundGestational 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. MethodsPregnant 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. Key findingsGH 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. SignificanceGH 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.