TSPYL1 regulates steroidogenic gene expression and male factor fertility in mice

Abstract

Abstract Objective To determine the importance of Testis-specific, Y-encoded-like 1 (TSPYL1) in survival and male fertility in mice. Design Experimental prospective study. Setting Research laboratories in University Medical Faculty. Animals We generated Tspyl1 knockout (KO) mouse lines by CRISPR/Cas9. The lines were maintained by pairing heterozygous mice to provide wild-type control and knockout males for comparison. Intervention None. Main Outcome Measures Mendelian ratio, body and testis weight, histology, sperm motility, mating tests, pregnancy outcome, transcript levels of genes for testosterone production and serum testosterone level. Results A variable percentage of Tspyl1 KO mice survived beyond weaning depending on the genetic background. Growth around weaning was retarded in KO mice but testes to body weight ratio remained normal, and complete spermatogenesis was revealed in testis histology. Sperms were collected from the cauda epididymis and significantly less % of sperms were progressively motile (19.6±18.3 %, n= 14 samples) as compared to wild-type (58.9±11.5 %, 11 samples, P < 0.0001). All 11 KO mice tested had defective mounting behaviour. From 11 KO males paired with a total of 88 females, only one litter was born as compared to 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. Conclusions TSPYL1 is critical for survival and reproductive success in mice. TSPYL1 enhances the expression of key steroidogenic genes in the mouse testis.