哺乳动物附睾特异GPx5功能及其调节机制的研究进展

doi:10.16431/j.cnki.1671-7236.2018.09.020

摘要/Abstract

摘要：

精子在附睾中的成熟过程是哺乳动物雄配子获得受精能力的关键。谷胱甘肽过氧化物酶-5（glutathione peroxidase-5，GPx5）作为附睾特异性表达的抗氧化酶具有强抗氧化作用，可调节附睾微环境中的活性氧浓度，保护精子免受脂质过氧化损伤，以维持精子DNA完整性。GPx5还可能对精子活力和顶体反应产生一定影响。GPx5基因的染色体定位及其外显子数存在一定的种间差异，其在不同物种、部位和发育期的表达具有特异性，受雄激素、PEA3因子和ETV4家族等调节。作者就哺乳动物附睾特异GPx5基因的结构与定位、表达特性、功能及其调节机制的研究进展进行综述，以期为进一步研究精子抗氧化机制和提高雄性动物繁殖力提供理论依据。

关键词: 附睾; GPx5基因; 表达特性; 抗氧化; 精子

Abstract:

The sperm maturation in the epididymis is the key to mammalian male gametes gaining fertility capacity.Glutathione peroxidase-5 (GPx5) has a strong antioxidant effect as an antioxidant enzyme specifically expressed in the epididymis,which can regulate the concentration of reactive oxygen species in the epididymis microenvironment and protect spermatozoa from lipid peroxidation to maintain DNA integrity of sperm.GPx5 may also have a certain effect on sperm motility and acrosome reaction.The chromosomal location and the number of exons of GPx5 gene have certain interspecific differences.The expression of GPx5 gene is specific in different species,parts and developmental stages.The gene expression is regulated by factors such as androgen,PEA3 factor and ETV4 family.The authors reviewed the research advance on the structure and location,expression characteristics,function and regulation mechanism of specific GPx5 gene of mammalian epididymis in order to provide theoretical basis for further study on sperm antioxidant mechanism and improving male animal fertility.

Key words: epididymis; GPx5 gene; expression characteristics; anti-oxidation; sperm

中图分类号:

S814.4

栾兆进, 张家新. 哺乳动物附睾特异GPx5功能及其调节机制的研究进展[J]. 《中国畜牧兽医》, 2018, 45(9): 2500-2506.

LUAN Zhaojin, ZHANG Jiaxin. Research Progress on Function and Regulation Mechanism of Specific GPx5 of Mammalian Epididymis[J]. , 2018, 45(9): 2500-2506.

参考文献

[1] 杨红文,金丹.哺乳动物Gpx基因家族进化选择和功能分歧研究[J].重庆师范大学学报(自然科学版),2012,29(2):36-41.YANG H W,JIN D.Evolutionary selection and functional divergence of Gpx gene family in mammals[J].Journal of Chongqing Normal University(Natural Science Edition),2012,29(2):36-41.(in Chinese)
[2] GHYSELINCK N B,DUFAURE J P.A mouse cDNA sequence for epididymal androgen regulated proteins related to glutathione peroxidase[J].Nucleic Acids Research,1990,18(23):7144.
[3] CHABORY E,DAMON C,LENOIR A,et al.Mammalian glutathione peroxidases control acquisition and maintenance of spermatozoa integrity[J].Journal of Animal Science,2010,88(4):1321-1331.
[4] RAY P D,HUANG B W,TSUJI Y.Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling[J].Cellular Signalling,2012,24(5):981-990.
[5] GHYSELINCK N B,DUFAURE I,LAREYRE J J,et al.Structural organization and regulation of the gene for the androgen-dependent glutathione peroxidase-like protein specific to the mouse epididymis[J].Molecular Endocrinology,1993,7(2):258-272.
[6] VERNET P,RIGAUDIERE N,GHYSELINCK N,et al.In vitro expression of a mouse tissue specific glutathione-peroxidase-like protein lacking the selenocysteine can protect stably transfected mammalian cells against oxidative damage[J]. Biochemistry and Cell Biology,1996,74(1):125.
[7] DREVET J R.The antioxidant glutathione peroxidase family and spermatozoa:A complex story[J].Molecular & Cellular Endocrinology,2006,250(1-2):70-79.
[8] PUGLISI R,MACCARI I,PIPOLO S,et al.The nuclear form of glutathione peroxidase 4 is associated with sperm nuclear matrix and is required for proper paternal chromatin decondensation at fertilization[J].Journal of Cellular Physiology,2012,227(4):1420-1427.
[9] NOBLANC A,PELTIER M,DAMONSOUBEYRAND C,et al.Epididymis response partly compensates for spermatozoa oxidative defects in snGPx4 and GPx5 double mutant mice[J].PLoS One,2012,7(6):e38565.
[10] CHABORY E,DAMON C,LENOIR A,et al.Epididymis seleno-independent glutathione peroxidase 5 maintains sperm DNA integrity in mice[J].Journal of Clinical Investigation,2009,119(7):2074-2085.
[11] LAHTI P P,SHARIATMADARI R,PENTTINEN J K,et al.Evaluation of the 5'-flanking regions of murine glutathione peroxidase five and cysteine-rich secretory protein-1 genes for directing transgene expression in mouse epididymis[J].Biology of Reproduction,2001,64(4):1115-1121.
[12] 郭笑,陈冬雪,韩笑,等.人谷胱甘肽过氧化物酶的生物信息学分析[J].北华大学学报(自然科学版),2016,17(6):750-755.GUO X,CHEN D X,HAN X,et al.Bioinformatics analysis of human glutathione peroxidase[J].Journal of Beihua University (Natural Science),2016,17(6):750-755.(in Chinese)
[13] HALL L,WILLIAMS K,PERRY A C,et al.The majority of human glutathione peroxidase type 5(GPX5) transcripts are incorrectly spliced:Implications for the role of GPX5 in the male reproductive tract[J].Biochemical Journal,1998,333(1):5-9.
[14] BERTANI G R,MARKLUND S,HU Z L,et al.Rapid communication:Mapping of the glutathione-peroxidase-5(GPx5) gene to pig chromosome 7[J].Journal of Animal Science,1999,77(10):2855.
[15] VAIMAN M,CHARDON P,ROTHSCHILD M F.Porcine major histocompatibility complex[J]. Revue Scientifique et Technique,1998,17(1):95-107.
[16] 赵金凤,张冬杰,谷溪,等.猪GPx5基因、FUT1基因和NCOA1基因的多态性分析[J].华北农学报,2008,23(4):69-71.ZHAO J F,ZHANG D J,GU X,et al.Analysis of polymorphism on GPx5,FUT1 and NCOA1 gene in swine(pig)[J].Acta Agriculturae Boreali-Sinica,2008,23(4):69-71.(in Chinese)
[17] 张春香,郭云雁,白元生,等.绵羊GPx5基因克隆、生物信息学分析及表达特性的研究[J].畜牧兽医学报,2014,45(7):1075-1083.ZHANG C X,GUO Y Y,BAI Y S,et al.Clone,bioinformatics analysis and expression characteristics of ovine GPx5[J].Acta Veterinaria et Zootechnica Sinica,2014,45(7):1075-1083.(in Chinese)
[18] 张蕊.哺乳动物细胞HEK293-F瞬时表达人IL-4[D].天津:南开大学,2012.ZHANG R.Mammalian cells HEK293-F transiently express human IL-4[D].Tianjin:Nankai University,2012.(in Chinese)
[19] GRAUGNARD D E,PIANTONI P,BIONAZ M,et al.Adipogenic and energy metabolism gene networks in longissimus lumborum during rapid post-weaning growth in Angus and Angus×Simmental cattle fed high-starch or low-starch diets[J].BMC Genomics,2009,10:142.
[20] SCHWAAB V,LAREYRE J J,VERNET P,et al.Characterization,regulation of the expression and putative roles of two glutathione peroxidase proteins found in the mouse epididymis[J]. Journal of Reproduction and Fertility Supplement,1998,53(1):157-162.
[21] ZHANG T,CHABORY E,BRITAN A,et al.GPX5,the selenium-independent glutathione peroxidase-encoding single copy gene is differentially expressed in mouse epididymis[J].Reproduction Fertility & Development,2008,20(5):615.
[22] OKAMURA N,IWAKI Y,HIRAMOTO S,et al.Molecular cloning and characterization of the epididymis-specific glutathione-like protein in porcine epididymal fluid[J]. Biochimica et Biophysica Acta General Subjects,1997,1336(1):99-109.
[23] MANASKOVA-POSTLEROVA P,DAVIDOVA N,JONAKOVA V.Biochemical and binding characteristics of boar epididymal fluid proteins[J].Journal of Chromatography B Analytical Technologies in the Biomedical & Life Sciences,2011,879(1):100-106.
[24] 栗瑞兰,张通,范晓梅,等.GPx5在成年绵羊附睾中的表达与蛋白定位[J].中国农业科学,2015,48(24):4989-4995.LI R L,ZHANG T,FAN X M,et al.Study on expression of glutathione peroxidase type-5(GPx5) and protein localization in epididymis of adult sheep[J].Scientia Agricultura Sinica,2015,48(24):4989-4995.(in Chinese)
[25] 张建新,王茜,荀文娟,等.GPxs家族基因在山羊不同组织和睾丸不同发育时期的表达特性研究[J].畜牧兽医学报,2011,42(5):650-657.ZHANG J X,WANG Q,GOU W J,et al.The expression of glutathione peroxidases family genes in different tissues and testes at different stages of male goats[J].Acta Veterinaria et Zootechnica Sinica,2011,42(5):650-657.(in Chinese)
[26] 张春香,张国林,郭丽娜,等.基于高通量转录组测序的山羊睾丸和附睾头差异表达基因分析[J].畜牧兽医学报,2014,45(3):391-401.ZHANG C X,ZHANG G L,GUO L N,et al.Study on differentially expressed genes between caprine testis and epididymis caput based on transcriptomes with high-throughput RNA-Seq technology[J].Acta Veterinaria et Zootechnica Sinica,2014,45(3):391-401.(in Chinese)
[27] KOZIOROWSKA-GILUN M,GILUN P,FRASER L,et al.Antioxidant enzyme activity and mRNA expression in reproductive tract of adult male european bison (Bison bonasus,Linnaeus 1758)[J].Reproduction in Domestic Animals,2013,48(1):7-14.
[28] GRIGNARD E,MORIN J,VERNET P,et al.GPx5 orthologs of the mouse epididymis-restricted and sperm-bound selenium-independent glutathione peroxidase are not expressed with the same quantitative and spatial characteristics in large domestic animals[J].Theriogenology,2005,64(4):1016.
[29] VERNET P,FAURE J,DUFAURE J,et al.Tissue and developmental distribution,dependence upon testicular factors and attachment to spermatozoa of GPx5,a murine epididymis-specific glutathione peroxidase[J].Molecular Reproduction & Development,1997,47(1):87.
[30] 乌亚罕,史振丹,乌丽雅苏,等.GPx5基因在绵羊附睾上的时空表达特性[J].西北农林科技大学学报(自然科学版),2017,45(4):1-10.WU Y H,SHI Z D,WU L Y S,et al.Temporal and spatial expression of GPx5 gene in sheep epididymis[J].Journal of Northwest A & F University(Natural Science Edition),2017,45(4):1-10.(in Chinese)
[31] 范晓梅,栗瑞兰,张通,等.GPx5在内蒙古绒山羊附睾中的表达[J].中国农业大学学报,2017,22(10):84-90.FAN X M,LI R L,ZHANG T,et al.Expression of GPx5 in the epididymis of Inner Mongolia cashmere goats[J].Journal of China Agricultural University,2017,22(10):84-90.(in Chinese)
[32] AITKEN R J.Gpx5 protects the family jewels[J].Journal of Clinical Investigation,2009,119(7):1849.
[33] VERNET P,ROCK E,MAZUR A,et al.Selenium-independent epididymis-restricted glutathione peroxidase 5 protein (GPx5) can back up failing Se-dependent GPxs in mice subjected to selenium deficiency[J].Molecular Reproduction & Development,1999,54(4):362.
[34] 王咏梅.自由基与谷胱甘肽过氧化物酶[J].解放军药学学报,2005,21(5):369-371.WANG Y M.Free radicals and glutathione peroxi-dase[J].Pharmaceutical Journal of Chinese People's Liberation Army,2005,21(5):369-371.(in Chinese)
[35] TAYLOR A,ROBSON A,HOUGHTON B C,et al.Epididymal specific,selenium-independent GPx5 protects cells from oxidative stress-induced lipid peroxidation and DNA mutation[J].Human Reproduction,2013,28(9):2332-2342.
[36] GHARAGOZLOO P,GUTIERREZ-ADAN A,CHAMPROUX A,et al.A novel antioxidant formulation designed to treat male infertility associated with oxidative stress:Promising preclinical evidence from animal models[J].Human Reproduction,2016,31(2):252-262.
[37] BARRANCO I,TVARIJONAVICIUTE A,PEREZ-PATINO C,et al.Glutathione peroxidase 5 is expressed by the entire pig male genital tract and once in the seminal plasma contributes to sperm survival and in vivo fertility[J].PLoS One,2016,11(9):e0162958.
[38] VILAGRAN I,CASTILLO-MARTIN M,PRIETO-MARTINEZ N,et al.Triosephosphate isomerase (TPI) and epididymal secretory glutathione peroxidase (GPx5) are markers for boar sperm quality[J].Animal Reproduction Science,2016,165:22.
[39] D'AMOURS O,FRENETTE G,BOURASSA S,et al.Proteomic markers of the functional sperm population in bovines 1.Comparison of low-and high-density spermatozoa following cryopreservation[J].Journal of Proteome Research,2018,17(1):177-188.
[40] WILLIAMS K,FRAYNE J,HALL L.Expression of extracellular glutathione peroxidase type 5(GPx5) in the rat male reproductive tract[J].Molecular Human Reproduction,1998,4(9):841.
[41] PERRY A C,JONES R,NIANG L S,et al.Genetic evidence for an androgen-regulated epididymal secretory glutathione peroxidase whose transcript does not contain a selenocysteine codon[J].Biochemical Journal,1992,285(3):863-870.
[42] CHAUVIN T R,GRISWOLD M D.Androgen-regulated genes in the murine epididymis[J].Biology of Reproduction,2004,71(2):560-569.
[43] RIGAUDIÈRE N,GHYSELINCK N B,FAURE J,et al.Regulation of the epididymal glutathione peroxidase-like protein in the mouse:Dependence upon androgens and testicular factors[J].Molecular & Cellular Endocrinology,1992,89(1-2):67-77.
[44] LAREYRE J J,CLAESSENS F,ROMBAUTS W,et al.Characterization of an androgen response element within the promoter of the epididymis-specific murine glutathione peroxidase 5 gene[J].Molecular & Cellular Endocrinology,1997,129(1):33-46.
[45] HINTON B T,LAN Z J,RUDOLPH D B,et al.Testicular regulation of epididymal gene expression[J].Journal of Reproduction & Fertility Supplement,1998,53(53):47.
[46] DREVET J R,LAREYRE J J,SCHWAAB V,et al.The PEA3 protein of the Ets oncogene family is a putative transcriptional modulator of the mouse epididymis-specific glutathione peroxidase gene GPx5[J].Molecular Reproduction & Development,2015,49(2):131-140.
[47] BJÖRKGREN I,SAASTAMOINEN L,KRUTSKIKH A,et al.Dicer1 ablation in the mouse epididymis causes dedifferentiation of the epithelium and imbalance in sex steroid signaling[J].PLoS One,2012,7(6):e38457.
[48] YANG L,FOX S A,KIRBY J L,et al.Putative regulation of expression of members of the Ets variant 4 transcription factor family and their downstream targets in the rat epididymis[J].Biology of Reproduction,2006,74(4):714-720.
[49] KOLASA A,MARCHLEWICZ M,ADLER G,et al.Expression of E-SOD,GPx5 mRNAs and immunoexpression of Cu/ZnSOD in epididymal epithelial cells of finasteride-treated rats[J]. Andrologia,2008,40(5):303-311.
[50] CHOI Y J,CHO S K,HWANG K C,et al.Nm23-M5 mediates round and elongated spermatid survival by regulating GPx-5 levels[J].FEBS Letters,2009,583(8):1292-1298.
[51] MAREMANDA K P,KHAN S,JENA G B.Role of zinc supplementation in testicular and epididymal damages in diabetic rat:Involvement of Nrf2,SOD1,and GPx5[J].Biological Trace Element Research,2016,173(2):452.
[52] PODDER B,SONG H Y,KIM Y S.Naringenin exerts cytoprotective effect against paraquat-induced toxicity in human bronchial epithelial BEAS-2B cells through NRF2 activation[J].Journal of Microbiology and Biotechnology,2014,24(5):605-613.