LncRNA8276 primes cell-cell adhesion for regulation of spermatogenesis

Human sperm concentration and motility have dropped dramatically (50%) in the past few decades, and environmental factors are involved in this decline. Long non-coding RNAs (lncRNA) have been discovered to be involved in many cellular processes including spermatogenesis.

This investigation aimed to explore the role of lncRNA8276 in murine spermatogenesis.

The expression of lncRNA8276 was modified by knockdown or overexpression in mouse testes and spermatogonial stem cells (C18-4 cell line). Sperm quality was determined in the F0 and F1 generations of mice. Furthermore, the underlying mechanisms were studied through gene expression and/or protein expression of spermatogenesis-related genes and cell junction-related genes by different methods.

In the current investigation, we discovered that sperm lncRNA8276 was decreased by NH₃ /H₂ S in three generations (F0, F1, and F2) of mouse sperm. In vivo testicular knockdown of lncRNA8276 led to a decline in sperm concentration and motility in both F0 (muF0) and F1 (muF1) generations Moreover, knockdown lncRNA8276 decreased the gene and protein levels of important genes related to cell-cell junctions and spermatogenesis. The data were further confirmed in mouse spermatogonia stem cell line C18-4 cells through knockdown of lncRNA8276.

Our study suggests that lncRNA8276 may be involved in cell-cell junction formation in the mouse testis to regulate spermatogenesis. It may be a target for the modification of spermatogenesis and male fertility, or male contraception. This investigation offers a potential therapeutic strategy for male infertility.