Prenatal iron deficiency causes sex‐dependent mitochondrial dysfunction and oxidative stress in fetal rat kidneys and liver

• DOI: 10.1096/fj.201701080r
• Publication Date: 2018-01-19T13:23:15Z
• Authors: Andrew G. Woodman; Richard Mah; Danae Keddie; Ronan M. N. Noble; Sareh Panahi; Ferrante S. Gragasin; Hélène Lemieux; Stephane L. Bourque
• Keywords: Male; 0301 basic medicine; Sex Characteristics; Mitochondria, Liver; Iron Deficiencies; Kidney; Rats; 3. Good health; Pregnancy Complications; Rats, Sprague-Dawley; Oxidative Stress; 03 medical and health sciences; Fetus; Liver; Pregnancy; Animals; Female

Prenatal iron deficiency alters fetal developmental trajectories, which results in persistent changes in organ function. Here, we studied the effects of prenatal iron deficiency on fetal kidney and liver mitochondrial function. Pregnant Sprague-Dawley rats were fed partially or fully iron-restricted diets to induce a state of moderate or severe iron deficiency alongside iron-replete control rats. We assessed mitochondrial function via high-resolution respirometry and reactive oxygen species generation via fluorescence microscopy on gestational d 21. Hemoglobin levels were reduced in dams in the moderate (-31%) and severe groups (-54%) compared with controls, which was accompanied by 55% reductions in fetal hemoglobin levels in both moderate and severe groups versus controls. Male iron-deficient kidneys exhibited globally reduced mitochondrial content and respiration, as well as increased cytosolic superoxide and decreased NO. Female iron-deficient kidneys exhibited complex II down-regulation and increased mitochondrial oxidative stress. Male iron-deficient livers exhibited reduced complex IV respiration and increased cytosolic superoxide, whereas female liver tissues exhibited no alteration in oxidant levels or mitochondrial function. These findings indicate that prenatal iron deficiency causes changes in mitochondrial content and function as well as oxidant status in a sex- and organ-dependent manner, which may be an important mechanism that underlies the programming of cardiovascular disease.-Woodman, A. G., Mah, R., Keddie, D., Noble, R. M. N., Panahi, S., Gragasin, F. S., Lemieux, H., Bourque, S. L. Prenatal iron deficiency causes sex-dependent mitochondrial dysfunction and oxidative stress in fetal rat kidneys and liver.