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Epididymosomes： transfer of fertility-modulating proteins to the sperm surface

Asian Journal of Andrology 2015年第5期17卷 720-725,I0006页

作者： patricia a martin-deleon Department of Biological Sciences University of Delaware Newark DE 19716 USA

A variety of glycosylphosphatidylinositol （GPI）-linked proteins are acquired on spermatozoa from epididymal luminal fluids （ELF） during sperm maturation. These proteins serve roles in immunoprotection and in key steps of fertilization such as capacitation, acrosomal exocytosis and sperm-egg interactions. Their acquisition on sperm cells is mediated both by membrane vesicles （epididymosomes, EP） which were first reported to dock on the sperm surface, and by lipid carriers which facilitate the transfer of proteins associated with the membrane-free fraction of ELF. While the nonvesicular fraction is more efficient, both pathways are dependent on hydrophobic interactions between the GPI-anchor and the external lipid layer of the sperm surface. More recently proteomic and hypothesis-driven studies have shown that EP from several mammals carry transmembrane （TM） proteins, including plasma membrane Ca^2＋-ATPase 4 （PMCA4）. Synthesized in the testis, PMCA4 is an essential protein and the major Ca^2＋ efflux pump in murine spermatozoa. Delivery of PMCA4 to spermatozoa from bovine and mouse EP during epididymal maturation and in vitro suggests that the docking of EP on the sperm surface precedes fusion, and experimental evidence supports a fusogenic mechanism for TM proteins. Fusion is facilitated by CD9, which generates fusion-competent sites on membranes. On the basis of knowledge of PMCA4＇s interacting partners a number of TM and membrane-associated proteins have been identified or are predicted to be present, in the epididymosomal cargo deliverable to spermatozoa. These Ca^2＋-dependent proteins, undetected in proteomic studies, play essential roles in sperm motility and fertility, and their detection highlights the usefulness of the hypothesis-driven approach.

关键词： epididymal maturation epididymal secretory proteins GPI-linked proteins lipid carrier membrane-associated proteins PMCA4 transmembrane proteins

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Ultrastructural changes and asthenozoospermia in murine spermatozoa lacking the ribosomal protein L29/HIP gene

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Asian Journal of Andrology 2014年第6期16卷 925-926页

作者： Rolands G Aravindan Catherine B Kirn-Safran Michelle A Smith patricia a martin-deleon Department of Biological Sciences University of Delaware NewarkDE 19716 USA.

Dear Editor, We present here the first report linking a specific gene, ribosomal protein L29 （Rp129）, also known as Hip （heparin/heparan sulfate interacting protein）, to the mammalian sperm flagellar morphological anomaly termed the ＂dag＂ defect. In addition, we show that loss of Rp/29 invariably results in low sperm motility with infertility accompanying this abnormality.

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Anatase titanium dioxide nanoparticles in mice： evidence for induced structural and functional sperm defects after short-, but not long-, term exposure

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Asian Journal of Andrology 2015年第2期17卷 261-268,I0009页

作者： Michelle A Smith Rowan Michael Rolands G Aravindan Soma Dash Syed I Shah Deni S Galileo patricia a martin-deleon Department of Biological Sciences University of Delaware Newark DE USA Departments of Physics and Astronomy and of Material Science Engineering University of Delaware Newark DE USA.

锐钛型钛二氧化物纳米颗粒（TNPs）广泛应用在商业领域，并且存在于不同的产品中。为明确更小剂量的锐钛型钛二氧化物纳米颗粒（ATNPs）间隔一定距离进入体内到达阴囊后是否能诱导精子缺陷的发生，雄性成年小鼠持续3天腹腔内注射100％A... 详细信息

锐钛型钛二氧化物纳米颗粒（TNPs）广泛应用在商业领域，并且存在于不同的产品中。为明确更小剂量的锐钛型钛二氧化物纳米颗粒（ATNPs）间隔一定距离进入体内到达阴囊后是否能诱导精子缺陷的发生，雄性成年小鼠持续3天腹腔内注射100％ATNP（2．5或5mg／kg），然后在注射后1周、2周、3周或5周（长时间暴露）或者是注射后24小时、48小时或120小时（短时间暴露）处死。透射电镜表明在注射后120小时收集到的阴囊脂肪组织中，附睾组织和附睾液均出现炎症反应。在注射后120小时和3周后，睾丸组织间质间隙增大。利用末端脱氧核糖核酸转移酶介导的缺口末端标记技术发现在注射后的雄鼠体内阳性（即凋亡）精子（P=0．002）和间质细胞（P=O．04）数目均显著增加。与对照组相比，短时间暴露而不是长时间暴露的附睾尾部精子鞭毛异常、过量胞浆残余（ERC）的发生率增加，精子无顶体反应的发生率增加（呈剂量依赖性）。ERC与无顶体反应是否存在相关性目前尚不清楚。与对照组相比，暴露120小时组快速运动精子数量和线粒体膜电位均显著下降（P〈0．05），同时，活性氧水平显著增加（P〈0．00001）。这些结果表明在注射后4．8天，ANTP能够引发不育的精子结构和功能的异常，并且通过氧化应激造成DNA的损伤。同时，在暴露后的10天到5周末检测到精子的异常，这表明精子的这种异常是暂时性的。

关键词：胞浆小滴氧化应激精子活动缺陷无顶体反应

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Prohibitin(PHB)interacts with AKT in mitochondria to coordinately modulate sperm motility

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Asian Journal of Andrology 2020年第6期22卷 583-589页

作者： Xiao-Hui Li Ran-Ran Chai Guo-Wu Chen Ling-Fei Zhang Wen-Jing Tan-Tai Hui-Juan Shi patricia a martin-deleon Wai-Sum O Hong Chen Department of Anatomy Histology and EmbryologyKey Laboratory of Medical Imaging Computing and Computer Assisted Intervention of ShanghaiSchool of Basic Medical SciencesShanghai Medical CollegeFudan UniversityShanghai 200032China Shanghai Ji'Ai Genetics and IVF Institute Obstetrics and Gynecology HospitalInstitute of Reproduction and DevelopmentFudan UniversityShanghai 200011China Key Lab of Reproduction Regulation of NPFPC-Shanghai Institute of Planned Parenthood Research Fudan University Reproduction and Development InstitutionShanghai 200032China Department of Biological Sciences University of DelawareNewarkDE 19716-2590USA School of Biomedical Sciences The University of Hong KongHong Kong SARChina

Prohibitin(PHB),an evoluti on arily con served mitochondrial inner membra ne protein,is highly expressed in cells that require strong mitoch on drial ***,we dem on strated that the deleti on of Phb in spermatocytes results in impaired mitochondrial *** addition,PHB expression in the mitochondrial sheath of human sperm has a significantly negative correlation with mitochondrial reactive oxygen species levels,but a positive one with mitochondrial membrane potential and sperm *** results suggest that mitochondrial PHB expression plays a role in sperm ***,the mechanism of PHB-mediated regulation of sperm motility remai ns unk ***,we dem on strate for the first time that PHB interacts with protei n kinase B(AKT)and exists in a complex with phospho-PHB(pT258)and phospho-AKT in the mitochondrial sheath of murine sperm,as determined using colocalization and coimmunoprecipitation *** blocking AKT activity using wortmannin(a phosphatidylinositol 3-kinase[PI3K]inhibitor),murine sperm have significantly(P<0.05)decreased levels of phospho-PHB(pT258)and the total and progressive ***,significantly(P<0.05)lower levels of phospho-PI3K P85 subunit a+γ(pY199 and pY46)and phospho-AKT(pS473;pT308)are found in sperm from infertile asthenospermic and oligoasthenospermic men compared with no rmospermic subjects,which suggest a reduced activity of the PI3K/AKT pathway in these in fertile ***,these sperm from infertile subjects also have a significantly(P<0.05)lower level of phospho-PHB(pT258).Collectively,our findings suggest that the interaction of PHB with AKT in the mitochondrial sheath is critical for sperm motility,where PHB phosphorylation(pT258)level and PI3K/AKT activity are key regulatory factors.

关键词： male in fertility prohibitin(PHB) protein kinase B(AKT) sperm motility

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