Ovol1regulates meiotic pachytene progression during spermatogenesis by repressing Id2 expression

Abstract

Previous studies have shown that a targeted deletion of Ovol1(previously known as movo1), encoding a member of the Ovo family of zinc-finger transcription factors, leads to germ cell degeneration and defective sperm production in adult mice. To explore the cellular and molecular mechanism of Ovol1 function, we have examined the mutant testis phenotype during the first wave of spermatogenesis in juvenile mice. Consistent with the detection of Ovol1 transcripts in pachytene spermatocytes of the meiotic prophase, Ovol1-deficient germ cells were defective in progressing through the pachytene stage. The pachytene arrest was accompanied by an inefficient exit from proliferation, increased apoptosis and an abnormal nuclear localization of the G2-M cell cycle regulator cyclin B1, but was not associated with apparent chromosomal or recombination defects. Transcriptional profiling and northern blot analysis revealed reduced expression of pachytene markers in the mutant, providing molecular evidence that pachytene differentiation was defective. In addition,the expression of Id2 (inhibitor of differentiation 2), a known regulator of spermatogenesis, was upregulated in Ovol1-deficient pachytene spermatocytes and repressed by Ovol1 in reporter assays. Taken together, our studies demonstrate a role for Ovol1 in regulating pachytene progression of male germ cells, and identify Id2 as a Ovol1target.

Disruption of the murine dynein light chain gene Tcte3-3 results in asthenozoospermia

“…One of the genes that are down regulated is Tcte3. Interestingly, down regulation of Tcte3 expression already occurs even if apoptosis is minimal (Li et al 2005). Further support for the correlation between Tcte3 and apoptosis comes from studies using ethylene glycol monomethyl ether (EGME).…”

Not all germ cells are created equal: Aspects of sexual dimorphism in mammalian meiosis

“…Similarly, in females, the requirement for regulated and staged progression through prophase I must be balanced with the need to induce the expression of genes that will invoke dictyate arrest, for example. With this is mind, it is surprising that a disproportionate number of mutations affecting gene regulation cause male-specific, rather than femalespecific, meiotic defects (for example, the transcription factor OVOL1; Dai et al 1998, Li et al 2005. One possibility is that female meiosis is not as well-studied as male meiosis because it occurs during embryonic development and is therefore not as accessible for many studies, particularly those involving small-scale biochemical analysis.…”

Transcription and post-transcriptional regulation of spermatogenesis

“…The defects are most pronounced in the testis, where there is massive germ-cell degeneration, accompanied by dramatically reduced sperm cell count and subfertility. Because the loss of germ cells in the adult testes of Ovol1-mutant mice complicates analysis of Ovol1 function in spermatogenesis, recently Li et al (2005) examined Ovol1 function during the first wave of spermatogenesis. They found that germ cells lacking OVOL1 from postnatal mice exhibit poor exit from mitotic proliferation in spermatogonia and approximately 50 per cent of the spermatocytes are incapable of proceeding through the late pachytene stage (figure 2).…”