Mycophenolate mofetil exposure on embryonic and fetal ear development in rats during pregnancy.

Abstract

To explore the pathogenesis of microtia, in this study, the different concentrations of mycophenolate mofetil (MMF) exposure on the development of rat embryonic and fetal ears, in order to establish a drug-induced microtia model, and provide a basis for further exploring the pathogenesis of microtia. The pregnant rat model was established in this study, 56 pregnant SD rats were randomly divided into 4 groups: control group and MMF (50, 100, and 200 mg/kg) group. Solutions were administered to the rats by oral gavage at gestation day (GD) 9 and GD 10 8:00 a.m, once a day. On GD 10.5 and GD 14.5, embryos were evaluated for neural crest development. On GD 20.5, fetuses were evaluated for overall survival and development with particular focus on ear development via morphologic, skeletal, and histologic investigation. Some animals were allowed to deliver their litters and offspring were evaluated on postnatal day 18 for ear development. A total of 56 pregnant rats, 14 in each group, were included in the study. As a result, depending on MMF dose increase, in experimental groups, it was determined that the statistically significant the development of the first and second branchial arches and derived tissues of the embryo, overall survival, ear development, and length and weight of fetuses. Imaging of MMF groups revealed statistically significant differences in the development of the skull and auditory vesicles of MMF treated fetuses. Histologically, MMF affected the proliferation and differentiation of chondrocytes and the expression of type II collagen. Mycophenolate mofetil can lead to the hypoplasia of rat embryos, fetuses, and auricle in a dose-dependent. MMF may affect the migration and proliferation of cranial neural crest cells, and then lead to microtia. MMF may induce the establishment of an animal model of microtia.