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Cellular mechanisms regulating sperm-zona pellucida interaction

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Asian Journal of Andrology 2011年第1期13卷 88-96页

作者： Andrew T Reid Kate Redgrove R John Aitken brett nixon Reproductive Science Group Discipline of Biological Sciences School of Environmental and Life Sciences University of Newcastle Callaghan NSW 2308 Australia ARC Centre of Excellence in Biotechnology and Development Discipline of Biological Sciences School of Environmental and Life Sciences University of Newcastle CaUaghan NSW 2308 Australia

For mammalian spermatozoa to exhibit the ability to bind the zona pellucida （ZP） they must undergo three distinct phases of maturation, namely, spermatogenesis （testis）, epididymal maturation （epididymis） and capacitation （female reproductive tract）. An impressive array of spermatozoa surface remodeling events accompany these phases of maturation and appear critical for recognition and adhesion of the outer vestments of the oocyte, a structure known as the ZP. It is becoming increasingly apparent that species-specific zona adhesion is not mediated by a single receptor. Instead, compelling evidence now points toward models implicating a multiplicity of receptor-ligand interactions. This notion is in keeping with emerging research that has shown that there is a dynamic aggregation of proteins believed to be important in sperm-ZP recognition to the regions of sperm that mediate this binding event. Such remodeling may in turn facilitate the assembly of a multimeric zona recognition complex （MZRC）. Though formation of MZRCs raises questions regarding the nature of the block to polyspermy, formation and assembly of such a structure would no doubt explain the strenuous maturation process that sperm endure on their sojourn to functional maturity.

关键词： capacitation fertilization spermatozoa sperm-zona pellucida interaction

The 12th International Symposium on Spermatology

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Asian Journal of Andrology 2015年第4期17卷 519-520页

作者： R John Aitken Jim M Cummins brett nixon Priority Research Centre in Reproductive Science Discipline of Biological Sciences and HunterMedical Research Institute University of NewcastleNSW 2308 Australia Division of Veterinary andBiomedical Sciences Murdoch University MurdochWA. Australia.

The 12th International Symposium of Spermatology continued the excellent tradition of this meeting since its inception in 1969 when the first Symposium was held in Italy under the Chairmanship of Professor Baccio Baccetti. This unique Symposium is held every 4 years and serves as a beacon for sperm cell biologists from all over the world, regardless of which species, animal or plant, they are working on. This willingness to embrace the fundamental biology of this distinctive cell type without species limitations is one of the hallmarks of this Symposium. For sperm biologists - it is our Olympics. The meeting in Newcastle, NSW brought together around 300 biologists from more than 22 different countries covering North and South America, Africa, Europe, Asia and Australia. Given the considerable distances and high cost involved in travelling to the East Coast of NSW, this was an outstanding outcome. The Symposium featured a series of 31 plenary lectures culminating in the prestigious Thaddeus Mann Memorial Lecture, which was delivered with typical grace and brilliance by Professor Masaru Okabe.

关键词： International Symposium Spermatology

Role of the epididymis in sperm competition

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Asian Journal of Andrology 2007年第4期9卷 493-499页

作者： Russell C. Jones Jean-Louis Dacheux brett nixon Heath W. Ecroyd Discipline of Biological Sciences University of Newcastle Callaghan 2308 Australia UMR INRA-CNRS 6073 Physiologie de la Reproduction et des Comportements Nouzilly 37380 France Department of Chemistry University of Adelaide Adelaide 5005 Australia

Although it is generally understood that the testes recruited kidney ducts for reproductive function during the evolution of vertebrates, little is understood of the biological significance of the adaptation. In the context of the evolution of the mammalian epididymis, this report provides evidence that a major role of the epididymis is to enhance a male＇s chance of achieving paternity in a competitive mating system. A unique example of sperm cooperation in monotremes is used as evidence that the epididymis produces sperm competition proteins to form groups of 100 sperm into bundles that have a forward motility nearly thrice that of individual spermatozoa. As it required 3-h incubation in vitro under capacitation conditions to release motile sperm from the bundles, it is suggested that the monotremes provide an example of capacitation that is quite different from capacitation in higher mammals. It is suggested that variation between species in the intensity of sperm competition could explain the variation that occurs between species in the amount of post-testicular sperm maturation and storage in the epididymis, an explanation of why the human epididymis does not play as important a role in reproduction as the epididymis of most mammals. （Asian J Androl 2007 July; 9： 493-499）

关键词： epididymis sperm maturation sperm storage capacitation sperm competition sperm cooperation

The role of the molecular chaperone heat shock protein A2 （HSPA2） in regulating human sperm-egg recognition

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Asian Journal of Andrology 2015年第4期17卷 568-573页

作者： brett nixon Elizabeth G Bromfield Matthew D Dun Kate A Redgrove Eileen A McLaughlin R John Aitken priority Research Centre in Reproductive Science School of Environmental and Life Sciences Discipline of Biological Sciences University of Newcastle CallaghanNSW 2308 Australia Priority Research Centre in Chemical Biology School of Environmental and Life Sciences Discipline of Biological Sciences University of NewcastleCallaghan NSW 2308 Australia Hunter Cancer Research Alliance School of Biomedical Sciences and Pharmacy Faculty of Health and Medicine NSW Australia

One of the most common lesions present in the spermatozoa of human infertility patients is an idiopathic failure of sperm-egg recognition. Although this unique cellular interaction can now be readily by-passed by assisted reproductive strategies such as intracytoplasmic sperm injection （ICSI）, recent large-scale epidemiological studies have encouraged the cautious use of this technology and highlighted the need for further research into the mechanisms responsible for defective sperm-egg recognition. Previous work in this field has established that the sperm domains responsible for oocyte interaction are formed during spermatogenesis prior to being dynamically modified during epididymal maturation and capacitation in female reproductive tract. While the factors responsible for the regulation of these sequential maturational events are undoubtedly complex, emerging research has identified the molecular chaperone, heat shock protein A2 （HSPA2）, as a key regulator of these events in human spermatozoa. HSPA2 is a testis-enriched member of the 70 kDa heat shock protein family that promotes the folding, transport, and assembly of protein complexes and has been positively correlated with in vitro fertilization （IVF） success. Furthermore, reduced expression of HSPA2 from the human sperm proteome leads to an impaired capacity for cumulus matrix dispersal, sperm-egg recognition and fertilization following both IVF and ICSI. In this review, we consider the evidence supporting the role of HSPA2 in sperm function and explore the potential mechanisms by which it is depleted in the spermatozoa of infertile patients. Such information offers novel insights into the molecular mechanisms governing sperm function.

关键词： egg fertilization heat shock protein A2 molecular chaperone sperm sperm-egg interactions

Proteomic changes in mammalian spermatozoa during epididymal maturation

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Asian Journal of Andrology 2007年第4期9卷 554-564页

作者： R. John Aitken brett nixon Minjie Lin Adam J. Koppers Yun H. Lee Mark A. Baker The ARC Centre of Excellence in Biotechnology and Development University of Newcastle Newcastle NSW 2308Australia Discipline of Biological Sciences University of Newcastle Newcastle NSW 2308 Australia

Epididymal maturation is associated with the activation of a cAMP-induced tyrosine phosphorylation cascade, which is ultimately associated with the expression of capacitation-dependent sperm functions, such as hyperactivated movement and acrosomal exocytosis. As spermatozoa progress through the epididymis they first acquire the capacity to phosphorylate tyrosine on targets on the principal piece, followed by the midpiece. By the time these cells have reached the cauda epididymidis they can phosphorylate the entire tail from neck to endpiece. This particular pattern of phosphorylation is associated with the ontogeny of fully functional spermatozoa that are capable of fertilizing the oocyte. Proteomic analyses indicate that this change is associated with the phosphorylation of several mitochondrial proteins, creation of a mitochondrial membrane potential and activation of mitochondrial free radical generation. At least in rodent species, activation of sperm mitochondria appears to be a particularly important part of epididymal maturation. （Asian J Androl 2007 July; 9： 554-564）

关键词： epididymis mitochondria spermatozoa tyrosine phosphorylation

Knockout of glutathione peroxidase 5 down-regulates the piRNAs in the caput epididymidis of aged mice

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Asian Journal of Andrology 2020年第6期22卷 590-601页

作者： Chen Chu Lu Yu Joelle Henry-Berger Yan-Fei Ru Ayhan Kocer Alexandre Champroux Zhi-Tong Li Miao He Sheng-Song Xie Wu-Bin Ma Min-Jie Ni Zi-Mei Ni Yun-Li Guo Zhao-Liang Fei Lan-Tao Gou Qiang Liu Samanta Sharma Yu Zhou Mo-Fang Liu Charlie Degui Chen Andrew L Eamens brett nixon Yu-Chuan Zhou Joel R Drevet Yong-Lian Zhang State Key Laboratory of Molecular Biology Shanghai Key Laboratory of Molecular AndrologyCAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China Genetics Reproduction and Development Laboratory CNRS UMR 6293-INSERM U1103-Universite Clermont AuvergneClermont-Ferrand 63001France Institute of Neuroscience State Key Laboratory of NeuroscieneeShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031China Key Laboratory of Agricultural Animal Genetics Breedingand Reproduction of the Ministry of Education and Key Laboratory of Swine Genetics and Breeding of the Ministry of AgricultureHuazhong Agricultural UniversityWuhan 430070China Department of Cellular and Molecular Medicine University of CaliforniaSan DiegoLa JollaCA 92093-0651USA Department of Anatomy Histology and EmbryologyShanghai Jiao long University School of MedicineShanghai Key Laboratory of Reproductive MedicineShanghai 200025China department of Cancer Biology Dana-Farber Cancer InstituteBostonMA 02215USA Department of Genetics Harvard Medical SchoolBostonMA 02115USA Priority Research Centre for Reproductive Sciences School of Environmental and Life SciencesThe University of NewcastleCallaghanNSW 2308Australia.

The mammalian epididymis not only plays a fun dame ntal role in the maturati on of spermatozoa,but also provides protecti on agai nst various *** foremost among these is the threat posed by oxidative stress,which arises from an imbalance in reactive oxygen species and can elicit damage to cellular lipids,proteins,and nucleic *** mice,the risk of oxidative damage to spermatozoa is mitigated through the expression and secretion of glutathione peroxidase 5(GPX5)as a major luminal scavenger in the proximal caput epididymidal ***,the loss of GPX5^-/-mediated protection leads to impaired DNA integrity in the spermatozoa of aged Gpx57 *** explore the underlying mechanism,we have conducted transcriptomic analysis of caput epididymidal epithelial cells from aged(13 months old)Gpx5^-/-m *** analysis revealed the dysregulation of several thousand epididymal mRNA transcripts,in eluding the downregulation of a subgroup of piRNA pathway gen es,in aged Gpx5^-/-*** agreeme nt with these fin dings,we also observed the loss of piRNAs,which potentially bind to the P-element-induced wimpy testis(PlWI)-like proteins PIWIL1 and *** absence of these piRNAs was correlated with the elevated mRNA levels of their putative gene targets in the caput epididymidis of Gpx5^-/-***,the oxidative stress response genes tend to have more targeting piRNAs,and many of them were among the top increased genes upon the loss of GPX5^-/-.Taken together,our findings suggest the existence of a previously uncharacterized somatic piRNA pathway in the mammalian epididymis and its possible invoIvement in the aging and oxidative stress-mediated responses.

关键词： epididymis GPX5 oxidative stress piRNA PIWI-interacting RNA small noncoding RNA