A New Deletion of the Mouse Y Chromosome Long Arm Associated With the Loss ofSstyExpression, Abnormal Sperm Development and Sterility

Abstract

The mouse Y chromosome carries 10 distinct genes or gene families that have open reading frames suggestive of retained functionality; it has been assumed that many of these function in spermatogenesis. However, we have recently shown that only two Y genes, the testis determinant Sry and the translation initiation factor Eif2s3y, are essential for spermatogenesis to proceed to the round spermatid stage. Thus, any further substantive mouse Y-gene functions in spermatogenesis are likely to be during sperm differentiation. The complex Ssty gene family present on the mouse Y long arm (Yq) has been implicated in sperm development, with partial Yq deletions that reduce Ssty expression resulting in impaired fertilization efficiency. Here we report the identification of a more extensive Yq deletion that abolishes Ssty expression and results in severe sperm defects and sterility. This result establishes that genetic information (Ssty?) essential for normal sperm differentiation and function is present on mouse Yq.

Promoter ChIP-chip analysis in mouse testis reveals Y chromosome occupancy by HSF2

“…2 A). These stages contain round spermatids (21), and our findings are in accordance with those of previous studies showing that Ssty, Sly, and Slx transcripts are present only during spermatogenesis, predominantly in round spermatids (2,20,22,23). Importantly, the Hsf2 expression coincided with transcription of the multicopy genes in stages containing round spermatids (II-VIII) (Fig.…”

“…3B). Our results show that in addition to the similar alterations in Ssty2, Sly, and Slx expression, the Hsf2 Ϫ/Ϫ head abnormalities were equivalent to the flattened sperm head phenotype of the XY RIII qdel mutant (23,25,26). The Hsf2 Ϫ/Ϫ sperm head anomaly (Fig.…”

“…2 A) (2-4, 20, 22, 23), where the chromatin undergoes a substantial remodeling process (27). The MSYq resident genes have been proposed to have a role in chromatin remodeling (2,23), indicating that HSF2 could, through direct regulation of Ssty2 and/or Sly, be involved in chromatin remodeling during spermatogenesis. Deletions in the MSYq region have emerged as the most common genetic cause for spermatogenic failures in the human population worldwide, resulting in oligo-or azoospermia (30).…”

“…2B). Moreover, XY RIII qdel mutant mice display abnormalities in the sperm heads (23,25,26), which has been interpreted to reflect incorrect chromatin organization in the nucleus (2,25). We examined the Hsf2 Ϫ/Ϫ sperm morphology by assessing the degree of sperm abnormalities in hematoxylin-stained sperm smears from WT and Hsf2 Ϫ/Ϫ males.…”

Transcription and post-transcriptional regulation of spermatogenesis

“…Interestingly, some of its target genes (Ssty2 and Sly) are part of multi-copy gene clusters in the malespecific region of the long arm of the mouse Y chromosome (MSYq) that are expressed exclusively during spermatogenesis. Previous studies have shown that deletion of the MSYq region results in sperm head defects and impaired fertility in mice (Toure et al 2004). Likewise, Hsf2 mutant mice are hypofertile and have a high proportion of sperm with head defects.…”