Heat-shock protein HSPA4 is required for progression of spermatogenesis
Heat-shock protein HSPA4 is required for progression of spermatogenesis
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DOI：
10.1530/rep-11-0023
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发表时间：
2011-07-01
期刊：
影响因子：
3.8
通讯作者：
Adham, Ibrahim M.
中科院分区：
文献类型：
--
作者：
Held, Torsten;Barakat, Amal Z.;Adham, Ibrahim M.
热休克蛋白110（HSP 110）家族成员在ATP水解循环中作为哺乳动物和酵母HSP 70分子伴侣的核苷酸交换因子（NEF）。在这项研究中，我们描述了小鼠HSP 110家族成员HSPA 4在睾丸发育过程中的表达模式以及HSPA 4缺乏对男性生育力的影响。HSPA 4在所有检测的组织中普遍表达。在生殖腺的产前和产后发育过程中，HSPA 4在体细胞和生殖细胞中都有表达，但在产前生殖腺的生殖细胞中表达量更高。对Hspa 4缺陷小鼠的分析显示，所有在杂交C57 BL/6 Jx 129/Sv遗传背景上的纯合子小鼠都明显健康。虽然HSPA 4早在E13.5在雄性性腺中表达，但Hspa 4（-/-）和对照同窝仔之间缺乏组织学差异表明Hspa 4缺乏不会损害生殖母细胞或其向精原细胞的发育。值得注意的是，越来越多的Hspa 4缺陷的男性表现出受损的生育能力，而女性是生育能力。与野生型同窝小鼠相比，不育的Hspa 4缺陷小鼠的精子总数及其活力显著降低。幼年Hspa 4（-/-）小鼠粗线期精母细胞大多数不能完成第一次减数分裂前期而发生凋亡。此外，下调转录水平的基因已知表达的精母细胞在后期阶段的前期I和后减数分裂精子细胞导致建议，大多数生精细胞的发展是在后期阶段的减数分裂前期I。这些结果提供了证据表明，HSPA 4是正常精子发生所必需的。生殖（2011年）142 133-144
Heat-shock protein 110 (HSP110) family members act as nucleotide exchange factors (NEF) of mammalian and yeast HSP70 chaperones during the ATP hydrolysis cycle. In this study, we describe the expression pattern of murine HSPA4, a member of the HSP110 family, during testis development and the consequence of HSPA4 deficiency on male fertility. HSPA4 is ubiquitously expressed in all the examined tissues. During prenatal and postnatal development of gonad, HSPA4 is expressed in both somatic and germ cells; however, expression was much higher in germ cells of prenatal gonads. Analyses of Hspa4-deficient mice revealed that all homozygous mice on the hybrid C57BL/6Jx129/Sv genetic background were apparently healthy. Although HSPA4 is expressed as early as E13.5 in male gonad, a lack of histological differences between Hspa4(-/-) and control littermates suggests that Hspa4 deficiency does not impair the gonocytes or their development to spermatogonia. Remarkably, an increased number of the Hspa4-deficient males displayed impaired fertility, whereas females were fertile. The total number of spermatozoa and their motility were drastically reduced in infertile Hspa4-deficient mice compared with wild-type littermates. The majority of pachytene spermatocytes in the juvenile Hspa4(-/-) mice failed to complete the first meiotic prophase and became apoptotic. Furthermore, down-regulation of transcription levels of genes known to be expressed in spermatocytes at late stages of prophase I and post-meiotic spermatids leads to suggest that the development of most spermatogenic cells is arrested at late stages of meiotic prophase I. These results provide evidence that HSPA4 is required for normal spermatogenesis. Reproduction (2011) 142 133-144