Testicular expression of long non–coding RNAs is affected by curative GnRHa treatment of cryptorchidism

BACKGROUND: Cryptorchidism is a frequent endocrinopathy in boys that has been associated with an increased risk of developing testicular cancer and infertility. The condition is curable by combined surgery and hormonal treatment during early pre-pubertal stages using gonadotropin releasing hormone agonist (GnRHa). However, whether the treatment also alters the expression of testicular long non-coding RNAs (lncRNAs) is unknown. To gain insight into the effect of GnRHa on testicular lncRNA levels, we re-analyzed an expression dataset generated from testicular biopsies obtained during orchidopexy for bilateral cryptorchidism. RESULTS: We identified EGFR-AS1, Linc-ROR, LINC00221, LINC00261, LINC00282, LINC00293, LINC00303, LINC00898, LINC00994, LINC01121, LINC01553, and MTOR-AS1 as potentially relevant for the stimulation of cell proliferation mediated by GnRHa based on their direct or indirect association with rapidly dividing cells in normal and pathological tissues. Surgery alone failed to alter the expression of these transcripts. CONCLUSION: Given that lncRNAs can cooperate with chromatin-modifying enzymes to promote epigenetic regulation of genes, GnRHa treatment may act as a surrogate for mini-puberty by triggering the differentiation of Ad spermatogonia via lncRNA-mediated epigenetic effects. Our work provides additional molecular evidence that infertility and azoospermia in cryptorchidism, resulting from defective mini-puberty cannot be cured with successful orchidopexy alone.