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Human sperm anatomy: ultrastructural localization of 1α,25-dihydroxyvitamin D3 receptor and its possible role in the human male gamete

机译:人体精子解剖:1α,25-二羟基维生素D3受体的超微结构定位及其在人类雄配子中的可能作用

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摘要

Previous studies have suggested that 1α,25-dihydroxyvitamin D3[1,25(OH)2D3] has a role in reproductive function. Gonadal insufficiencies were observed as a result of 1,25(OH)2D3 deficiency and in 1,25(OH)2D3 receptor (VDR) null mutant mice. To study human sperm anatomy at the molecular level, we first evaluated the ultrastructural localization of VDR by immunogold electron microscopy using a monoclonal antibody against amino acids 344–424 of human VDR, in normozoospermic samples. Intriguingly, VDR was associated predominantly with the cell nucleus. In fact, it is known that VDR is a transcription factor, and that in vitamin-D-depleted animals, VDR is largely localized in the cell nucleus. To assess the significance of VDR in the male gamete, we investigated the role of 1,25(OH)2D3/VDR in sperm survival and capacitation. Our results revealed that the action of 1,25(OH)2D3 depended on its concentration because although lower doses induced cholesterol efflux, protein phosphorylation and sperm survival, a higher concentration seemed to be ineffective or did not show an increased effect. These results increase our knowledge of human sperm anatomy at the molecular level and suggest that 1,25(OH)2D3/VDR may have an important role in sperm survival and the acquisition of fertilizing ability.
机译:先前的研究表明1α,25-二羟基维生素D3 [1,25(OH)2D3]在生殖功能中起作用。 1,25(OH)2D3缺乏和1,25(OH)2D3受体(VDR)空突变小鼠中观察到性腺功能不全。为了在分子水平上研究人类精子的解剖结构,我们首先使用抗人VDR氨基酸344–424的单克隆抗体通过免疫金电子显微镜对正常精子样本中VDR的超微结构定位进行了评估。有趣的是,VDR主要与细胞核相关。实际上,已知VDR是转录因子,并且在维生素D缺乏的动物中,VDR主要位于细胞核中。为了评估VDR在雄性配子中的重要性,我们研究了1,25(OH)2D3 / VDR在精子存活和获能中的作用。我们的结果表明1,25(OH)2D3的作用取决于其浓度,因为尽管较低的剂量会引起胆固醇外流,蛋白质磷酸化和精子存活,但较高的浓度似乎无效或未显示出增加的作用。这些结果增加了我们在分子水平上对人类精子解剖学的了解,并表明1,25(OH)2D3 / VDR可能在精子存活和获得受精能力中起重要作用。

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