Mild maternal iron deficiency anemia induces DPOAE suppression and cochlear hair cell apoptosis by caspase activation in young guinea pigs

• We use a mild maternal iron deficiency anemia model to induce hearing impairment in young guinea pigs.
• Mild iron deficiency anemia induces hair cell apoptosis and caspase-3/9 activation.
• Apoptosis may play a key role for inhibition of hair cell development caused by mild iron deficiency anemia.

Iron deficiency (ID) anemia (IDA) alters auditory neural normal development in the mammalian cochlea. Previous results suggest that mild maternal IDA during pregnancy and lactation altered the hearing and nervous system development of the young offspring, but the mechanisms underlying the association are incompletely understood. The objective of this study was to evaluate the role of apoptosis in the development of sensory hair cells following mild maternal IDA during pregnancy and lactation. We established a maternal anemia model in female guinea pigs by using a mild iron deficient diet. The offspring were weaned on postnatal day (PND) 9 and then was given the iron sufficient diet. Maternal blood samples were collected on gestational day (GD) 21, GD 42, GD 63 and PND 9, serum level of iron (SI) or hemoglobin (Hb) was measured. Blood samples of pups were collected on PND 9 for SI measurement. On PND 24, pups were examined the distortion product otoacoustic emission (DPOAE) task, and then the cochleae were harvested for assessment of apoptosis by immunohistochemistry of cysteine–aspartic acid proteases 3/9 (caspase-3/9) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay, and by double immunofluorescence for the colocalization of TUNEL and caspase-3. Blood samples of pups were collected on PND 24 for SI and Hb measurements. Here we show that mild maternal IDA during pregnancy and lactation resulted in hearing impairment, decreased hair cell number, caspase-3/9 activation and increased apoptotic cell number of young guinea pigs. These results indicate a key role for apoptosis in inhibition of hair cell development, caused by mild maternal IDA during pregnancy and lactation.