Testis

Molecular Characterization of Heat Shock-like Factor Encoded on the Human Y Chromosome, and Implications for Male Infertility

Abstract
Azoospermia and oligospermia are major causes of male infertility. Some genes located on the Y chromosome are suggested as candidates for them. Recently, HSFY, which is similar to the HSF (heat shock transcription factor) family, has been mapped on the human Y chromosome as multi-copies. However, newly available sequence data deposited on NCBI shows that only the HSFY gene located on Yq has a long open reading frame containing a HSF-type DNA binding domain. HSFY is similar to LW-1 on the human X chromosome and a murine HSFY-like sequence (mHSFYL), 4933413G11Rik, on the mouse chromosome 1. LW-1 and mHSFYL have 53% and 70% homology to HSFY for amino acid sequences of their presumed DNA-binding domains, respectively. Comparison of the presumed DNA binding domains unveiled that the three HSF-like factors, HSFY, LW-1 and mHSFYL belong to a different class than conventional HSFs. When we screened for deletions on the Yq of males suffering from infertility, we found that HSFY was involved in interstitial deletions on the Y chromosomes for two azoospermic males who had DBY, USP9Y and DAZ but did not have RBMY located on the AZFb. Expression analysis of HSFY, LW-1 and mHSFYL unveiled that they are expressed predominantly in testis. Furthermore, immunnohistochemistry of HSFY in testis showed that its expression is restricted to both Sertoli cells and spermatogenic cells, and that it exhibits a stage-dependent translocation from the cytoplasm to the nucleus in spermatogenetic cells during spermatogenesis. These results may suggest that deletion of HSFY is involved in azoospermia or oligospermia.

Key words: Testis • Spermatogenesis

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