The difference in expression of long noncoding RNAs in rat semen induced by high-fat diet was associated with metabolic pathways.

BACKGROUND: Obesity, a common metabolic disease, is a known cause of male infertility due to its associated health risk. Long noncoding RNAs (lncRNAs) have also been reported to be associated with male reproductive diseases; however, their role in the association between high-fat diet-induced obesity (DIO) and male reproduction remains unclear.

METHODS: We used microarray analysis to compare the expression levels of lncRNAs and mRNAs in the spermatozoa of rats with DIO and normal rats. We selected a few lncRNAs that were obviously up-regulated or down-regulated, and then used RT-PCR to verify the accuracy of their expression. We then performed a functional enrichment analysis of the differentially expressed mRNAs using gene ontology and pathway analysis. Finally, target gene predictive analysis was used to explore the relationship between lncRNAs and mRNAs.

RESULTS: The results revealed a statistically significant difference in the fasting blood glucose level in rats with DIO and control rats. We found that 973 lncRNAs and 2,994 mRNAs were differentially expressed in the sperm samples of the DIO rats, compared to the controls. GO enrichment analysis revealed 263 biological process terms, 39 cellular component terms, and 40 molecular function terms (p < 0.01) in the differentially expressed mRNAs. The pathway analysis showed that metabolic pathways were most enriched in protein-coding genes.

DISCUSSION: To the best of our knowledge, this is the first report to show differences in the expression levels of lncRNAs and mRNAs in the sperms of rats with DIO and normal rats, and to determine the expression profile of lncRNAs in the sperm of rats with DIO. Our results have revealed a number of lncRNAs and pathways associated with obesity-induced infertility, including metabolic pathways. These pathways could be new candidates that help cope with and investigate the mechanisms behind the progression of obesity-induced male infertility.