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Exposure to Gestational Intermittent Hypoxia Does Not Impair the Metabolic Function or Accelerate the Biological Ageing Process of Offspring of Either Sex
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Resumo(s)
Obstructive sleep apnea (OSA), marked by intermittent hypoxia, is associated with obesity, type 2 diabetes and metabolic associated fatty liver disease. In pregnancy, it remains underdiagnosed despite links to gestational diabetes, hypertension, and foetal growth restriction. Intermittent hypoxia may alter foetal programming and increase the risk of long-term metabolic issues in offspring. This study evaluates the effects of gestational OSA on offspring metabolic function, focusing on weight gain, glucose homeostasis, insulin sensitivity, hepatic glucose metabolism, inflammation and oxidative stress. Experiments were performed on pregnant female Wistar rats submitted to a chronic intermittent hypoxia (CIH) protocol during the last 2 weeks of pregnancy. Offspring were evaluated for body weight, glucose tolerance and insulin sensitivity at 1, 3, and 12 months of age. Liver western blot analysis was performed to assess markers of glucose metabolism (glucokinase, pyruvate kinase and glucose-6-phosphatase), inflammation (NF-kB, IL-1R, IL-6R, TNF-ɑR and NRLP3) and antioxidant enzymes (catalase, SOD-1 and iNOS). CIH did not modify body weight, glucose tolerance and insulin sensitivity at 1, 3 and 12 months of age, except for a transient increase in glucose intolerance observed in 3-month-old females, which was attenuated by 12 months. Moreover, no evidence was found of modifications caused by gestational CIH on markers of hepatic glucose metabolism, inflammation or antioxidant defence. However, there was a gradual increase in inflammation with age. No sexual dimorphism was observed. Overall, these findings suggest that gestational CIH does not predispose offspring to long-term metabolic dysfunction later in life and does not affect biological ageing, regardless of sex.
Descrição
Funding Information: This work has received funding from Programa Estart\u00E9gico IBGM, Escalera de Excelencia supported by Consejeria de Educaci\u00F3n de la Junta de Castilla y Le\u00F3n, Escalera de Excelencia (CCVC8485), Consejeria de Educaci\u00F3n de la Junta de Castilla y Le\u00F3n, Junta de Castilla y Le\u00F3n and from the Universidad de Valladolid (UVa PROYEMER\u20102021\u201057) in Spain and from the Research Unit INOVA4Health supported by the Portuguese Foundation for Science and Technology (UIDB/04462/2020 and UIDP/04462/2020) and the Associated laboratory LS4Future supported by the Portuguese Foundation for Science and Technology (LA/P/0087/2020), financially supported by the Funda\u00E7\u00E3o para a Ci\u00EAncia e Tecnologia/Minist\u00E9rio da Educa\u00E7\u00E3o, Ci\u00EAncia e Inova\u00E7\u00E3o in Portugal. J.F.S. is supported with a contract from the Funda\u00E7\u00E3o para a Ci\u00EAncia e Tecnologia with the reference CEEC IND/02428/2018. Funding: Funding Information: A. Rocher and S.V. Conde are the guarantors of the study and take full responsibility for the work, including the study design, access to data, and the decision to submit and publish the manuscript. The authors would like to thank Oscar A. R\u00EDos for his valuable assistance with the experimental work. Open access publication funding provided by FCT (b\u2010on). Publisher Copyright: © 2025 The Author(s). Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.
Palavras-chave
chronic intermittent hypoxia hepatic function life-course metabolic dysfunction offspring pregnancy sex General Medicine Cognitive Neuroscience Behavioral Neuroscience SDG 3 - Good Health and Well-being