Chronic fetal hypoxia and antenatal Vitamin C exposure differentially regulate molecular signalling in the lung of female lambs in early adulthood

慢性胎儿缺氧和产前维生素 C 暴露对成年早期母羔肺中的分子信号传导有差异调节

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作者:Erin V McGillick, Sandra Orgeig, Beth J Allison, Kirsty L Brain, Melanie R Bertossa, Stacey L Holman, Ashley S Meakin, Michael D Wiese, Youguo Niu, Nozomi Itani, Katie L Skeffington, Christian Beck, Kimberly J Botting-Lawford, Janna L Morrison #, Dino A Giussani #

Conclusion

There are differential effects of antenatal Vitamin C on molecular markers in the lungs of female lambs from normoxic and hypoxic pregnancy in early adulthood.

Methods

Chronically catheterised pregnant sheep were exposed to normoxia (N; n = 20) or hypoxia (H; n = 18; 10% O2) ± maternal daily i. v. saline (N = 11; H = 8) or Vitamin C (VC; NVC = 9; HVC = 10) from 105 to 138 days (term, ∼145 days). Lungs were collected from female lambs 9 months after birth (early adulthood). Lung tissue expression of genes and proteins regulating oxidative stress, mitochondrial function, hypoxia signalling, glucocorticoid signalling, surfactant maturation, inflammation and airway remodelling were measured.

Results

Chronic fetal hypoxia upregulated lung expression of markers of prooxidant, surfactant lipid transport and airway remodelling pathways in early adulthood. Antenatal Vitamin C normalized prooxidant and airway remodelling markers, increased endogenous antioxidant, vasodilator and inflammatory markers, and altered regulation of hypoxia signalling and glucocorticoid availability.

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