TSPYL1 regulates steroidogenic gene expression and male factor fertility in mice

Abstract

To determine the importance of testis-specific, Y-encoded-like 1 (TSPYL1) in survival and male factor fertility in mice. Experimental prospective study. Research laboratories in a university medical faculty. We generated Tspyl1 knockout (KO) mouse lines by CRISPR/Cas9. The lines were maintained by pairing heterozygous mice to provide wild-type control and KO males for comparison. None. Mendelian ratio, body and testis weight, histology, sperm motility, mating tests, pregnancy outcome, transcript levels of genes for testosterone production, and serum testosterone level. A variable percentage of Tspyl1 KO mice survived beyond weaning depending on the genetic background. Growth around weaning was retarded in KO mice, but the testes-to-body weight ratio remained normal and complete spermatogenesis was revealed in testis histology. Sperm was collected from the cauda epididymis, and a significantly smaller percentage of sperm was progressively motile (22.3% ± 18.3%, n = 14 samples) compared with wild type (58.9% ± 11.5%, 11 samples). All 11 KO mice tested had defective mounting behavior. From 11 KO males paired with a total of 88 females, only one litter was born, compared with 53 litters sired by 11 age-matched wild-type males. Expression of Star, Cyp11a1, Cyp17a1, Hsd3b6, and Hsd17b3 in the KO testis was significantly reduced, while serum testosterone level was within the normal range. TSPYL1 is critical for survival and reproductive success in mice. TSPYL1 enhances the expression of key steroidogenic genes in the mouse testis.