Am J Physiol Heart Circ Physiol. 2025 Nov 26. doi: 10.1152/ajpheart.00644.2025. Online ahead of print.
ABSTRACT
Adverse conditions within the embryonic environment can alter embryogenesis, programming systemic physiological changes that may manifest as disease states in adult life. The process of developmental programming represents an important factor underlying cardiometabolic diseases, many of which are leading causes of death globally. Importantly, there is evidence that males are less tolerant to certain environmental perturbations during embryogenesis, mirrored by sex differences in the incidence of certain cardiometabolic diseases. Understanding sex differences in programmed responses in mammalian models is complicated by maternal compensation and placental factors. Avian models offer a valuable comparable system in which such effects are not present. Here, we investigate the influence of developmental hypoxia and hypothermia in programming cardiovascular structure and function in the domestic chicken (Gallus gallus domesticus). In agreement to mammalian studies, adult males but not females show pathological mitochondrial morphology and respiratory capacity, ventricular hypertrophy and reduced body weight programmed by embryonic hypothermia and hypoxia. Notably, adult males but not females incubated under combined hypoxia and hypothermia display reduced left ventricle size, more spherical mitochondria and a reduction in mitochondrial complex IV activity in cardiomyocytes. Adult females incubated under hypothermic conditions show higher protein levels of mitochondrial complex V and do not display the same level of telomere shortening in comparison to males incubated under identical conditions. These data not only represent novel findings in birds but demonstrate the utility of the avian model for understanding sex differences in developmental stress responses, revealing common responses among endothermic amniotes.
PMID:41297037 | DOI:10.1152/ajpheart.00644.2025