TSPYL1 regulates steroidogenic gene expression and male factor fertility in mice

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OBJECTIVE: To determine the importance of testis-specific, Y-encoded-like 1 (TSPYL1) in survival and male factor fertility in mice. DESIGN: Experimental prospective study. SETTING: Research laboratories in a 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 KO males for comparison. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Mendelian ratio, body and testis weight, histology, sperm motility, mating tests, pregnancy outcome, transcript levels of genes for testosterone production, and serum testosterone level. RESULT(S): 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. CONCLUSION(S): TSPYL1 is critical for survival and reproductive success in mice. TSPYL1 enhances the expression of key steroidogenic genes in the mouse testis.

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