Decreased piRNAs in Infertile Semen Are Related to Downregulation of Sperm MitoPLD Expression.

Decreased piRNAs in Infertile Semen Are Related to Downregulation of Sperm MitoPLD Expression.
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不育精液中 piRNA 的减少与精子 MitoPLD 表达的下调有关

DOI:
10.3389/fendo.2021.696121
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发表时间:
2021
影响因子:
5.2
通讯作者:
Gao F
Gao F
中科院分区:
医学2区
文献类型:
--
作者:
Hong Y;Wu Y;Zhang J;Yu C;Shen L;Chen H;Chen L;Zhou X;Gao F

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目前,男性不育的分子机制仍然知之甚少。我们先前的研究表明,PIWI相互作用RNA(piRNA)在不育患者的精浆中下调,可以作为男性不育的分子生物标志物。然而,piRNA失调的来源和机制仍然不清楚。在这项研究中,我们发现外泌体以高浓度存在于人精浆中,并证实piRNA主要存在于精浆的外泌体部分中。此外,我们发现,与正常精子男性相比,弱精子症患者的外泌体中piRNA显著减少。通过系统地筛选正常精子症男性和弱精子症患者精子中的皮尔纳谱,我们发现piRNA在不育期间减少。最后,我们研究了精子中piRNA生物发生所必需的一些蛋白质的表达,因此确定了精子皮尔纳和MitoPLD蛋白水平之间的紧密相关性,表明MitoPLD功能的丧失可能导致精子中皮尔纳积累的严重缺陷。总之,本研究鉴定了弱精子症患者精子中piRNA和MitoPLD蛋白的平行减少,这可以提供关于精子运动性的病理生理学线索。
Currently, the molecular mechanisms underlining male infertility are still poorly understood. Our previous study has demonstrated that PIWI-interacting RNAs (piRNAs) are downregulated in seminal plasma of infertile patients and can serve as molecular biomarkers for male infertility. However, the source and mechanism for the dysregulation of piRNAs remain obscure. In this study, we found that exosomes are present in high concentrations in human seminal plasma and confirmed that piRNAs are predominantly present in the exosomal fraction of seminal plasma. Moreover, we showed that piRNAs were significantly decreased in exosomes of asthenozoospermia patients compared with normozoospermic men. By systematically screening piRNA profiles in sperms of normozoospermic men and asthenozoospermia patients, we found that piRNAs were parallelly reduced during infertility. At last, we investigated the expression of some proteins that are essential for piRNAs biogenesis in sperms and therefore identified a tight correlation between the levels of spermatozoa piRNA and MitoPLD protein, suggesting that the loss-of-function of MitoPLD could cause a severe defect of piRNA accumulation in sperms. In summary, this study identified a parallel reduction of piRNAs and MitoPLD protein in sperms of asthenozoospermia patients, which may provide pathophysiological clues about sperm motility.
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