Molecular Characterization of Heat Shock-Like Factor Encoded on the Human Y Chromosome, and Implications for Male Infertility1

生物 Y染色体 遗传学 基因 支持细胞 无精子症 分子生物学 无精子症因子 男性不育 打开阅读框 热冲击系数 精子发生 热休克蛋白 肽序列 不育 热休克蛋白70 内分泌学 怀孕
作者
Toshikatstu Shinka,Yoko Sato,Gang Chen,Takushi Naroda,Keigo Kinoshita,Yukiko Unemi,Keiko Tsuji,Kazunori Toida,Teruaki Iwamoto,Yutaka Nakahori
出处
期刊:Biology of Reproduction [Oxford University Press]
卷期号:71 (1): 297-306 被引量:79
标识
DOI:10.1095/biolreprod.103.023580
摘要

Azoospermia and oligospermia are major causes of male infertility. Some genes located on the Y chromosome are suggested as candidates. Recently, HSFY, which is similar to the HSF (heat shock transcription factor) family, has been mapped on the human Y chromosome as multicopies. However, newly available sequence data deposited at 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, immunhistochemistry 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.
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