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

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.

The potential regulatory role of the lncRNA-miRNA-mRNA axis in teleost fish

“…The liver is essential for fish fertility because it can synthesize vitelline and the precursor of vitelline, which is required for oocyte development and maturation ( 53 , 85 ). Compared with fertile fish livers, sterile fish livers were found to have fewer vacuoles and significantly lower serum vitellogenin levels in P. olivaceus ( 86 ). Moreover, ncRNAs (mRNAs, lncRNAs, circular RNAs, and miRNAs) were differentially expressed in infertile and fertile individuals P. olivaceus ).…”

“…The lncRNA-miRNA-mRNA ceRNA network was constructed with 92 lncRNAs, 14 mRNAs, and 4 miRNAs, which included the identified potentially functional ncRNAs in steroid biosynthesis pathways, such as pol-miR-133-3p, pol-miR-221-3p, XLOC_008437, XLOC_015293, and XLOC_019323. Among the target genes, armadillo repeat-containing protein 6 (ARMC6), propionyl-CoA carboxylase alpha chain (PCCA), tetratricopeptide repeat, ankyrin repeat and coiled-coil containing 2 (TANC2), transposable DNA element 5 (TNR5), and matrix metalloproteinase 28 (MMP28) were associated mainly with metabolism (fat and glycerophospholipid), signal transduction (complement and coagulation cascades), and immunity (RIG-I-like receptor signaling pathway) ( 86 ). These results indicate that fish infertility is related not only to histological structure, hormone secretion, and the steroid biosynthesis pathway but also to liver metabolism, immunity, and signal transduction, which may all be regulated by ncRNAs and their ceRNA network.…”