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Mycophenolate mofetil exposure on embryonic and fetal ear development in rats during pregnancy
Qian Chen1, Yang Zhang1, Youqi Luo1
1Department of Plastic and Cosmetic Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Insights
Mycophenolate mofetil (MMF) exposure during pregnancy caused dose-dependent microtia in rat offspring, affecting ear development and survival. This study establishes a drug-induced microtia model for further research into its pathogenesis.
Area of Science:
- Developmental biology
- Teratology
- Pharmacology
Background:
- Microtia, a congenital ear anomaly, lacks a fully understood pathogenesis.
- Investigating drug-induced models can elucidate developmental defects.
Purpose of the Study:
- To explore the pathogenesis of microtia by establishing a drug-induced model.
- To assess the effects of mycophenolate mofetil (MMF) on embryonic and fetal ear development in rats.
Main Methods:
- Pregnant Sprague-Dawley rats were administered varying doses of MMF (50, 100, 200 mg/kg) or a control solution.
- Embryos and fetuses were evaluated for development, survival, and specific ear morphology at different gestational and postnatal stages.
- Histological analysis examined chondrocyte proliferation, differentiation, and collagen type II expression.
Main Results:
- MMF exposure resulted in a dose-dependent decrease in embryonic and fetal survival and ear development.
- Significant developmental abnormalities were observed in the first and second branchial arches, skull, and auditory vesicles.
- MMF impacted chondrocyte biology and collagen type II expression, crucial for cartilage formation.
Conclusions:
- Mycophenolate mofetil induces microtia and other developmental defects in a dose-dependent manner in rats.
- MMF likely interferes with cranial neural crest cell migration and proliferation, leading to microtia.
- This study provides a valuable animal model for investigating microtia pathogenesis.
