New insights into the role of the Brdt protein in the regulation of development and spermatogenesis in the mouse

• The testes of Brdt mutant mice aged 8 weeks exhibited complete spermatocyte maturation arrest.
• Weights of testes and accessory glands and testosterone levels of the mutant mice aged 8 weeks were significantly reduced.
• The mutant mice had delayed puberty, with normal levels of testosterone and accessory gland weights at older ages.
• The presence of the BRDT protein was identified in the mice pituitary gland.

The bromodomain testis-specific (BRDT) protein belongs to the bromodomain extra-terminal (BET) family of proteins. It serves as a transcriptional regulator of gene expression during spermatogenesis, and is an essential factor for the normal spermatogenesis process. In this study, we characterized mice of several age groups who lacked the Brdt gene. The testes of Brdt mutant mice aged 8 weeks exhibited complete spermatocyte maturation arrest with a significantly increased number of apoptotic cells. The weights of the testes and accessory glands as well as the testosterone levels of the mutant mice were significantly lower compared to the normal mice. The mutant mice had delayed puberty, with normal levels of testosterone and accessory gland weights at the age of 14 and 28 weeks. The testes of the mutant mice at older ages also exhibited round spermatids. The presence of the BRDT protein was identified in the mice pituitary gland. Microarray analysis of mice pituitaries showed that 28 genes were down-regulated while 26 genes were up-regulated in the absence of the Brdt gene. Our results suggest that in addition to its critical role in the spermatogenesis process, the BRDT protein is also responsible for scheduling male puberty by regulation of the pituitary-gonad axis.