The Effect of Infertility on the Liver Structure, Endocrinology, and Gene Network in Japanese Flounder

SIMPLE SUMMARY: Infertility is a serious disorder that is characterized by the absence of fecundity in an individual. Not only does infertility in human beings affect reproduction, it also impacts hormonal secretion, metabolism, and the immune system. The doubled haploid (DH) that is induced by artificial mitogynogenesis or androgenesis in fish often results in infertility. The causes of infertility and its effects on other organs in the DH Japanese flounder (Paralichthys olivaceus) have not yet been established. Due to many aspects, the reproductive biology of this species is largely unknown or incomplete. Here, we compared the liver structure and hormone levels between fertile and infertile Japanese flounders, constructed ceRNA networks, and performed the integrated analysis of transcriptomics and proteomics. We concluded that gonadal infertility is associated with not only changes in histological structure and hormone secretion, but also changes in metabolism, immunity, and signal transduction networks in the liver. We also identified and characterized the differently expressed non-protein coding transcripts that are involved in liver functions in response to infertility. This study expanded our understanding of the molecular mechanisms of infertility on fish. ABSTRACT: The liver can synthesize vitellogenin, the precursor of vitellin, which is needed for oocyte development and maturation. Here, we investigated the effects of infertility on liver structure, hormone regulation, and gene and protein networks in Japanese flounder (Paralichthys olivaceus). Results showed that the liver of infertile fish had fewer vacuoles and significantly lower serum vitellogenin (VTG) level than in liver of fertile fish. Whole transcriptomics analysis between infertile and fertile groups identified 2076 significantly differentially expressed (DE) mRNAs, 431 DE lncRNAs, 265 DE circRNAs, and 53 DE miRNAs. Proteomics analysis identified 838 DE proteins. Integrated analysis of whole transcriptomics and proteomics revealed 60 significantly DE genes and proteins associated with metabolism, immunity, signal transduction, and steroid biosynthesis. Moreover, non-coding RNA (miRNAs, circRNA, and lncRNA) transcripts involved in metabolism, immunity, and signal transduction in infertile liver were identified. In conclusion, this study shows that gonadal infertility is associated with not only changes in histological structure and hormone secretion but also changes in metabolism, immunity, and signal transduction networks in the liver. These results provide valuable information concerning the mechanism underlying infertility in fish.