Hypoxia-induced epigenetic transgenerational miRNAs dysregulation involved in reproductive impairment of ovary

Hypoxia is a potent endocrine disruptor that is posing serious problems to the fish reproductive systems. Our previous studies reported that hypoxia could cause a transgenerational impairment of ovarian development and interfere hatching success in F2 offspring of marine medaka fish (Oryzias melastigma) through epigenetic regu-lation. As part of the epigenetic regulation, we investigated the involvement of microRNAs (miRNAs) in hypoxia-induced transgenerational reproductive impairments. In the present study, we used comparative small RNA sequencing to reveal that hypoxia caused miRNA dysregulation in ovaries of F0 hypoxia group and F2 trans -generational group. We found 4 common dysregulated miRNA in the F0 and F2 generations. Furthermore, in-tegrated miRNA-mRNA analysis, followed by gene ontology enrichment analysis on the hypoxia-dysregulated miRNA-target genes further highlighted the importance of these dysregulated miRNAs in biological processes related to reproduction. More importantly, we identified 3 miRNA-mRNA pairs (novel miRNA-525-DIAPH2, novel miRNA-525-MYOCD, and novel miRNA-525-RAI14) that might play epigenetic roles in hypoxia-induced reproductive impairment. For the first time, our findings suggested the involvement of miRNA in hypoxia-induced reproductive impairments may be inherited via a transgenerational manner.

Automated summary

Hypoxia can cause dysregulation of miRNA in the ovaries, leading to reproductive impairments in fish. Integrated miRNA-mRNA analysis reveals several dysregulated miRNA that are involved in biological processes related to reproduction. Furthermore, the study identifies specific miRNA-mRNA pairs that play a potential epigenetic role in hypoxia-induced reproductive impairments.