title: Mild Maternal Iron Deficiency Anemia Induces Hearing Impairment Associated with Reduction of Ribbon Synapse Density and Dysregulation of VGLUT3, Myosin VIIa, and Prestin Expression in Young Guinea Pigs.
abstract: Mild maternal iron deficiency anemia (IDA) adversely affects the development of cochlear hair cells of the young offspring, but the mechanisms underlying the association are incompletely understood. The aim of this study was to evaluate whether mild maternal IDA in guinea pigs could interrupt inner hair cell (IHC) ribbon synapse density and outer hair cell motility of the offspring. Here, we established a dietary restriction model that allows us to study quantitative changes in the number of IHC ribbon synapses and hearing impairment in response to mild maternal IDA in young guinea pig. The offspring were weaned on postnatal day (PND) 9 and then were given the iron-sufficient diet. On PND 24, pups were examined the hearing function by auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) measurements. Then, the cochleae were harvested for assessment of the number of IHC ribbon synapses by immunofluorescence, the morphology of cochlear hair cells, and spiral ganglion cells (SGCs) by scanning electron microscope and hematoxylin-eosin staining, the location, and expression of vesicular glutamate transporter (VGLUT) 3, myosin VIIa, and prestin by immunofluorescence and blotting. Here, we show that mild maternal IDA in guinea pigs induced elevated ABR threshold shifts, declined DPOAE level shifts, and reduced the number of ribbon synapses, impaired the morphology of cochlear hair cells and SGCs in offsprings. In addition, downregulation of VGLUT3 and myosin VIIa, and upregulation of prestin were observed in the cochlea of offsprings from mild maternal IDA in guinea pigs. These data indicate that mild maternal IDA in guinea pigs induced hearing impairment in offsprings, and this deficit may be attributed to the reduction of ribbon synapse density and dysregulation of VGLUT3, myosin VIIa, and prestin.
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, China. yufei@mail.cmu.edu.cn.
authors.forename: Fei
authors.initials: F
authors.lastname: Yu
authors.affiliation: Department of Otolaryngology, First Affiliated Hospital of China Medical University, No. 155, Nanjing North Street, Heping District, Shenyang, 110001, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Hao
authors.affiliation: Department of Otolaryngology, First Affiliated Hospital of China Medical University, No. 155, Nanjing North Street, Heping District, Shenyang, 110001, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, China.
authors.forename: Wenyue
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
mesh_terms: D000161:Acoustic Stimulation; D000367:Age Factors; D018798:Anemia, Iron-Deficiency / Q000150:complications*; D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem; D005260:Female; D006168:Guinea Pigs; D006199:Hair Cells, Auditory, Inner / Q000166:cytology; D034381:Hearing Loss / Q000209:etiology* / Q000473:pathology*; D008297:Male; D000081412:Myosin VIIa; D009218:Myosins / Q000378:metabolism*; D017084:Otoacoustic Emissions, Spontaneous; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D011571:Psychoacoustics; D013136:Spiral Ganglion / Q000166:cytology / Q000648:ultrastructure; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D015854:Up-Regulation / Q000502:physiology; D050496:Vesicular Glutamate Transport Proteins / Q000378:metabolism*
chemical_list: C000631455:MYO7A protein, human; D000081412:Myosin VIIa; C460879:SLC17A8 protein, human; D050496:Vesicular Glutamate Transport Proteins; D009218:Myosins
keywords: Hair cell; Iron deficiency anemia; Ribbon synapse