Involvement of the Bromodomain Testis-Specific (Brdt) Gene in Mice Spermatogenesis

Shimi Barda 1,2 Leah Yogev 1 Gedalia Paz 1 Haim Yavetz 1 Ofer Lehavi 1 Ron Hauser 1 Yael Salemnick 1 Haim Breitbart 2 Sandra Edith Kleiman 1
1Institute for the Study of Fertility, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center
2The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University

Introduction:The bromodomain testis-specific (BRDT) protein is a regulator of both meiotic divisions and post-meiotic chromatin remodeling. A recent study that used a model of knockout mice reported that complete absence of Brdt gene caused severe fertility impairment with complete arrest at the meiotic stage.

Aim:To assess the involvement of Brdt gene in the spermatogenesis process and its impact on the hormonal regulation of the reproductive system.

Materials & Methods:Brdt knockout mice were acquired from the International Knockout Mouse Consortium. Testicular biopsies were evaluated by RT-PCR, TUNEL and immunohistochemical staining. Testosterone in plasma was measured by ELISA.Gene expression levels differences between normal and mutant mice were assessed by microarray analysis.

Results:The testis of Brdt mutant mice aged 8 weeks exhibited complete spermatocyte maturation arrest with a significantly increased number of apoptotic cells. Their testosterone levels were significantly lower than those of the normal mice. Microarray analysis of the mice testis showed that 2083 genes were down regulated while 259 genes were up regulated in the absence of Brdt gene. However, at the age of 14 weeks, testosterone levels of the mutant mice were higher than those measured at the age of 8 weeks and similar to the testosterone levels of normal mice at the same age group. The testis of mutant mice aged 14 weeks exhibited round spermatids.

Conclusions:Brdt gene may have an impact on the hormonal reproductive axis, in addition to its essential role in the regulation of male germ cell differentiation.









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