lncRNA Impaired Male Fertility by Interfering with Sexual Behaviors in Mice.

Long non-coding (lnc) RNAs exhibit tissue-specific expression characteristics and have been shown to be involved in the regulation of various biological processes. The testis is one of the organs with the most abundant lncRNAs. However, the functions of many testis-specific or -enriched lncRNAs in male fertility remain undisclosed. In this study, we screened lncRNA () to investigate its roles in spermatogenesis and male fertility using knockout (KO) mice. We found that mainly acted as an intact lncRNA rather than a small protein, being highly expressed in various spermatogenic cells, which suggests its potential involvement in spermatogenesis. Unexpectedly, the deletion of did not impact spermatogenesis or sperm functions. Intriguingly, two-thirds of the male KO were infertile, which was ascribed to the lack of sexual behaviors rather than abnormalities in spermatogenesis or sperm functions. Further results reveal that, compared with wild-type mice, free testosterone content in serum was significantly reduced in the KO infertile (KO-I) mice, whereas it was remarkably elevated in the testes. Correspondingly, , a key gene that promotes testosterone synthesis, was dramatically upregulated. and which are responsible for testosterone metabolism, were downregulated in the testes. In addition, the expression of sex hormone-binding globulin was observably elevated in the testes of KO-I mice, which might partially explain the decrease in testosterone in the serum. These results suggest that disruptions in testosterone synthesis and metabolism might contribute to the loss of libido in KO-I mice. Our findings expand the understanding of lncRNA function and provide novel insights into the role of lncRNAs in male fertility, particularly in relation to hormonal turnover disorders that mediate sexual behavior defects.