Parental uveitis causes elevated hair loss in offspring of C57BL/6J mice

Our previous study demonstrated that parental uveitis in a susceptible population can cause hair loss and increase the susceptibility to experimental autoimmune uveitis (EAU) in offspring. However, it is unclear whether parental uveitis affects the development of offspring in an EAU-moderate-susceptible population. Herein, moderate-susceptible C57BL/6J mice were immunized with inter-photoreceptor retinoid binding protein (IRBP) 651-670 to develop EAU and were kept together for mating. Gross examination and histopathological changes of the offspring gestated with parental uveitis were observed to evaluate the impact of parental uveitis on the development of the offspring. Differentially expressed genes (DEGs) were screened by RNA sequencing in the affected skin and eyeball of the offspring on postnatal day 27. Adult offspring were injected 75 μg IRBP_651-670 to evaluate their susceptibility to EAU. Gross examination in the offspring revealed hair loss on postnatal days 11-31. Histopathological observation showed increased melanin granules and hair follicles of skin in the affected offspring with hair loss. Gene Ontology (GO) analysis in the skin revealed differential expression of genes involved in the mitotic cell cycle, response to endogenous stimulus, hair follicle development, and hair cycle. The DEGs in the skin were predominately associated with the cell cycle and peroxisome proliferator-activated receptor (PPAR) signaling pathway. The GO enrichment analysis in the eyeball showed differential expression of genes involved in the nervous system development, camera-type eye photoreceptor cell differentiation, neuron projection morphogenesis, axon development, and calcium-induced calcium release activity; enriched pathways included the circadian entrainment and glutamatergic synapses. No increased susceptibility to EAU in offspring gestated from parental remitting EAU was observed at a low-dose 75 μg IRBP induction. These results suggested that parental uveitis in a moderate-susceptible population could affect the skin development and DEG profiles of skin and eyeball related to the response to endogenous stimulus, the PPAR signaling pathway, and glutamatergic synapse, which provides the molecular evidence to explain the influence of parental uveitis on offspring development.