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Falling sper. counts twenty year. on： wher. ar. we now？

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Asian Jour.al of Andr.logy 2013年第2期15卷 204-207,I0006页

作者： r.john aitken Pr.or.ty r.sear.h Centr. in r.pr.ductive Science Discipline of Biological sciences University of Newcastle NSW 2308 Australia

Poor.semen quality is an attr.bute of the human condition that we shar.with our.closest pr.mate ancestor. and may be par. of our.evolutionar. inher.tance. This char.cter.stic may also r.flect the lack of selection pr.ssur. on male fer.ility in advanced societies that have gone thr.ugh the demogr.phic tr.nsition. In the futur., such tr.nds may be fur.her.exacer.ated by the widespr.ad use of Ar., which will impair.the elimination of low fecundity genotypes fr.m the human gene pool. Envir.nmental pollutants may also be influencing male fer.ility, however. neither.the chemical identity of these factor. nor.their.mechanism-of-action ar. fully under.tood.

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Apoptosis and DNA damage in human sper.atozoa

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Asian Jour.al of Andr.logy 2011年第1期13卷 36-42页

作者： r.john aitken Adam J Kopper. Ar. Centr. of Excellence in Biotechnology and Development Priority Research Centre in Reproductive Science Discipline of Biological Sciences School of Environmental and Life Sciences University of Newcastle Callaghan NSW 2308 Australia Depar.ment of Anatomy and Developmental Biology School of Biomedical Sciences Monash University Clayton VIC 3800 Australia

DNA damage is fr.quently encounter.d in sper.atozoa of subfer.ile males and is cor.elated with a r.nge of adver.e clinical outcomes including impair.d fer.ilization, disr.pted pr.implantation embr.onic development, incr.ased r.tes of miscar.iage and an enhanced r.sk of disease in the pr.geny. The etiology of DNA fr.gmentation in human sper.atozoa is closely cor.elated with the appear.nce of oxidative base adducts and evidence of impair.d sper.iogenesis. We hypothesize that oxidative str.ss impedes sper.iogenesis, r.sulting in the gener.tion of sper.atozoa with poor.y r.modelled chr.matin. These defective cells have a tendency to default to an apeptotic pathway associated with motility loss, caspase activation, phosphatidylser.ne exter.or.zation and the activation of fr.e r.dical gener.tion by the mitochondr.a. The latter.induces lipid per.xidation and oxidative DNA damage, which then leads to DNA fr.gmentation and cell death. The physical ar.hitectur. of sper.atozoa pr.vents any nucleases activated as a r.sult of this apoptotic pr.cess fr.m gaining access to the nuclear.DNA and inducing its fr.gmentation. It is for.this r.ason that a major.ty of the DNA damage encounter.d in human sper.atozoa seems to be oxidative. Given the impor.ant r.le that oxidative str.ss seems to have in the etiology of DNA damage, ther. should be an impor.ant r.le for.antioxidants in the tr.atment of this condition. If oxidative DNA damage in sper.atozoa is pr.viding a sensitive r.adout of systemic oxidative str.ss, the implications of these findings could str.tch beyond our.immediate goal of tr.ing to minimize DNA damage in sper.atozoa as a pr.lude to assisted conception ther.py.

关键词： apoptosis DNA damage oxidative str.ss sper.atozoa

Sper. cell biology： cur.ent per.pectives and futur. pr.spects

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Asian Jour.al of Andr.logy 2011年第1期13卷 3-5页

作者： r.john aitken r.lf r.Henkel Discipline of Biological Sciences University of Newcastle Newcastle NSW 2308 Australia Depar.ment of Medical Biosdences University of the Western Cape Bellville 7535 South Africa

Major.advances in biomolecular.techniques as well as in the sensitivity and accur.cy of mass spectr.meter. ar. tr.nsfor.ing the scientific landscape by fueling unpr.cedented advances in analytical biochemistr.--the ＇... 详细信息

关键词： Sper. cell biology per.pectives

Cellular.mechanisms r.gulating sper.-zona pellucida inter.ction

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Asian Jour.al of Andr.logy 2011年第1期13卷 88-96页

作者： Andr.w T r.id Kate r.dgr.ve r.john aitken Br.tt Nixon r.pr.ductive Science Gr.up Discipline of Biological Sciences School of Environmental and Life Sciences University of Newcastle Callaghan NSW 2308 Australia Ar. Centr. 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 sper.atozoa to exhibit the ability to bind the zona pellucida （ZP） they must under.o thr.e distinct phases of matur.tion, namely, sper.atogenesis （testis）, epididymal matur.tion （epididymis） and capacitation （female r.pr.ductive tr.ct）. An impr.ssive ar.ay of sper.atozoa sur.ace r.modeling events accompany these phases of matur.tion and appear.cr.tical for.r.cognition and adhesion of the outer.vestments of the oocyte, a str.ctur. known as the ZP. It is becoming incr.asingly appar.nt that species-specific zona adhesion is not mediated by a single r.ceptor. Instead, compelling evidence now points towar. models implicating a multiplicity of r.ceptor.ligand inter.ctions. This notion is in keeping with emer.ing r.sear.h that has shown that ther. is a dynamic aggr.gation of pr.teins believed to be impor.ant in sper.-ZP r.cognition to the r.gions of sper. that mediate this binding event. Such r.modeling may in tur. facilitate the assembly of a multimer.c zona r.cognition complex （MZr.）. Though for.ation of MZr.s r.ises questions r.gar.ing the natur. of the block to polysper.y, for.ation and assembly of such a str.ctur. would no doubt explain the str.nuous matur.tion pr.cess that sper. endur. on their.sojour. to functional matur.ty.

关键词： capacitation fer.ilization sper.atozoa sper.-zona pellucida inter.ction

Advantages of using the Cr.SPr.Cas9 system of genome editing to investigate male r.pr.ductive mechanisms using mouse models

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Asian Jour.al of Andr.logy 2015年第4期17卷 623-627页

作者： Samantha AM Young r.john aitken Masahito Ikawa Pr.or.ty r.sear.h Centr. in r.pr.ductive Science Discipline of Biological Sciences Faculty of Scienceand IT University of Newcastle Callaghan NSWAustralia Animal r.sour.e Centr. for.InfectiousDiseases Research Institute for Microbial DiseasesOsaka University Suita Osaka Japan.Correspondence: Prof. M Ikawa

Gene disr.ption technology has long been beneficial for.the study of male r.pr.ductive biology. However. because of the time and cost involved, this technology was not a viable method except in specialist labor.tor.es. The advent of the Cr.SPr.Cas9 system ofgene disr.ption has usher.d in a new er. of genetic investigation. Now, it is possible to gener.te gene-disr.pted mouse models in ver. tittle time and at ver. little cost. 1his Highlight ar.icle discusses the application of this technology to study the genetics of male fer.ility and looks at some of the futur. uses of this system that could be used to r.veal the essential and nonessential genetic components of male r.pr.ductive mechanisms.

关键词： Advantages investigate mechanisms

The 12th Inter.ational Symposium on Sper.atology

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Asian Jour.al of Andr.logy 2015年第4期17卷 519-520页

作者： r.john aitken Jim M Cummins Br.tt Nixon Pr.or.ty r.sear.h Centr. in r.pr.ductive Science Discipline of Biological Sciences and HunterMedical Research Institute University of NewcastleNSW 2308 Australia Division of Veter.nar. andBiomedical Sciences Murdoch University MurdochWA. Australia.

The 12th Inter.ational Symposium of Sper.atology continued the excellent tr.dition of this meeting since its inception in 1969 when the fir.t Symposium was held in Italy under.the Chair.anship of Pr.fessor.Baccio Baccetti. This unique Symposium is held ever. 4 year. and ser.es as a beacon for.sper. cell biologists fr.m all over.the wor.d, r.gar.less of which species, animal or.plant, they ar. wor.ing on. This willingness to embr.ce the fundamental biology of this distinctive cell type without species limitations is one of the hallmar.s of this Symposium. For.sper. biologists - it is our.Olympics. The meeting in Newcastle, NSW br.ught together.ar.und 300 biologists fr.m mor. than 22 differ.nt countr.es cover.ng Nor.h and South Amer.ca, Afr.ca, Eur.pe, Asia and Austr.lia. Given the consider.ble distances and high cost involved in tr.velling to the East Coast of NSW, this was an outstanding outcome. The Symposium featur.d a ser.es of 31 plenar. lectur.s culminating in the pr.stigious Thaddeus Mann Memor.al Lectur., which was deliver.d with typical gr.ce and br.lliance by Pr.fessor.Masar. Okabe.

关键词： Inter.ational Symposium Sper.atology

The r.le of the molecular.chaper.ne heat shock pr.tein A2 （HSPA2） in r.gulating human sper.-egg r.cognition

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Asian Jour.al of Andr.logy 2015年第4期17卷 568-573页

作者： Br.tt Nixon Elizabeth G Br.mfield Matthew D Dun Kate A r.dgr.ve Eileen A McLaughlin r.john aitken pr.or.ty r.sear.h Centr. in r.pr.ductive Science School of Environmental and Life Sciences Discipline of Biological Sciences University of Newcastle CallaghanNSW 2308 Australia Pr.or.ty r.sear.h Centr. in Chemical Biology School of Environmental and Life Sciences Discipline of Biological Sciences University of NewcastleCallaghan NSW 2308 Australia Hunter.Cancer.r.sear.h Alliance School of Biomedical Sciences and Pharmacy Faculty of Health and Medicine NSW Australia

One of the most common lesions pr.sent in the sper.atozoa of human infer.ility patients is an idiopathic failur. of sper.-egg r.cognition. Although this unique cellular.inter.ction can now be r.adily by-passed by assisted r.pr.ductive str.tegies such as intr.cytoplasmic sper. injection （ICSI）, r.cent lar.e-scale epidemiological studies have encour.ged the cautious use of this technology and highlighted the need for.fur.her.r.sear.h into the mechanisms r.sponsible for.defective sper.-egg r.cognition. Pr.vious wor. in this field has established that the sper. domains r.sponsible for.oocyte inter.ction ar. for.ed dur.ng sper.atogenesis pr.or.to being dynamically modified dur.ng epididymal matur.tion and capacitation in female r.pr.ductive tr.ct. While the factor. r.sponsible for.the r.gulation of these sequential matur.tional events ar. undoubtedly complex, emer.ing r.sear.h has identified the molecular.chaper.ne, heat shock pr.tein A2 （HSPA2）, as a key r.gulator.of these events in human sper.atozoa. HSPA2 is a testis-enr.ched member.of the 70 kDa heat shock pr.tein family that pr.motes the folding, tr.nspor., and assembly of pr.tein complexes and has been positively cor.elated with in vitr. fer.ilization （IVF） success. Fur.her.or., r.duced expr.ssion of HSPA2 fr.m the human sper. pr.teome leads to an impair.d capacity for.cumulus matr.x disper.al, sper.-egg r.cognition and fer.ilization following both IVF and ICSI. In this r.view, we consider.the evidence suppor.ing the r.le of HSPA2 in sper. function and explor. the potential mechanisms by which it is depleted in the sper.atozoa of infer.ile patients. Such infor.ation offer. novel insights into the molecular.mechanisms gover.ing sper. function.

关键词： egg fer.ilization heat shock pr.tein A2 molecular.chaper.ne sper. sper.-egg inter.ctions

Phosphor.lation of Izumo1 and its r.le in male nfer.ility

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Asian Jour.al of Andr.logy 2015年第5期17卷 708-710,I0005页

作者： Samantha AM Young john aitken Mar. A Baker pr.or.ty r.sear.h Centr. in r.pr.ductive Science Discipline of Biological Sciences Faculty of Science and IT University of Newcastle Callaghan NSW Australia Animal r.sour.e Centr. for.Infectious Diseases Research Institute for Microbial Diseases Osaka University Suita Osaka Japan

Izumol is a testis-specific gene pr.duct, whose function is essential for.sper.-egg fusion. Thr.ughout its lifespan, Izumol is posttr.nslationally modified, being both N-linked glycosylated on its extr.cellular.domain and phosphor.lated on the intr.cellular.C-ter.inal tail. Within the caput r.gions of the r.t epididymis, two phosphor.lation events have been documented. However. as sper. pass thr.ugh the epididymis, this cytoplasmic por.ion of Izumol has been shown to contain up to seven phosphor.lation sites. r.mar.ably, in the r.t, in cor.elation with these events, Izumol under.oes sub-cellular.r.-location, moving fr.m the head/tail r.gions of the sper.atozoa, to a pr.dominantly equator.al segment location once they have r.ached the caudal end of the epididymis.

关键词： epididymis Izumol LC-MS phosphor.lation pr.teomics

r.modeling of the plasma for.sper.-egg r.cognition： pr.teins membr.ne in pr.par.tion r.les of acr.somal

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Asian Jour.al of Andr.logy 2015年第4期17卷 574-582页

作者： Nongnuj Tanphaichitr.Kessir. Kongmanas Hathair.t Kr.evaisayawan Ar.or.r.d Saewu Clar.ssa Sugeng Jason Fer.andes Puneet Souda Jonathan B Angel Kym F Faull r.john aitken Julian Whitelegge Daniel Har.y Tr.sh Ber.er.Mar. Baker Chr.nic Disease Pr.gr.m Ottawa Hospital ResearchInstitute Ottawa Ontario Canada Depar.ment ofObstetr.cs and Gynaecology University of OttawaOntario Canada Depar.ment of Biochemistr. Microbiology and Immunology University of OttawaOntario Canada Depar.ment of Anatomy Faculty ofMedical Sciences Naresuan University PhitsanulokThailand Division of Infectious Diseases OttawaHospital - General Campus Ottawa Ontario Canada Pasar.w Mass Spectr.metr. Labor.tor. Universityof California Los Angeles California USA TheAr. Centr. of Excellence in Biotechnology andDevelopment School of Environmental and LifeSciences University of Newcastle Callaghan NewSouth Wales Australia Depar.ment of Cell Biologyand Biochemistr. Health Sciences Center Texas TechUniversity Texas USA Depar.ment of Animal ScienceUniver.ity of Califor.ia Davis California USA

The inter.ction of sper. with the egg＇s extr.cellular.matr.x, the zona pellucida （ZP） is the fir.t step of the union between male and female gametes. The molecular.mechanisms of this pr.cess have been studied for.the past six decades with the r.sults obtained being both inter.sting and confusing. In this ar.icle, we descr.be our.r.cent wor., which attempts to addr.ss two lines of questions fr.m pr.vious studies. Fir.t, because ther. ar. numer.us ZP binding pr.teins r.por.ed byvar.ous r.sear.her., how do these pr.teins act together.in sper.-ZP inter.ction？ Second, why do a number.of acr.somal pr.teins have ZP affinity？ Ar. they involved mainly in the initial sper.-ZP binding or.r.ther.in anchor.ng acr.some r.acting/r.acted sper.atozoa to the ZP？ Our.studies r.veal that a number.of ZP binding pr.teins and chaper.nes, extr.cted fr.m the anter.or.sper. head plasma membr.ne, coexist as high molecular.weight （HMW） complexes, and that these complexes in capacitated sper.atozoa have pr.fer.ntial ability to bind to the ZP. Zonadhesin （ZAN）, known as an acr.somal pr.tein with ZP affinity, is one of these pr.teins in the HMW complexes. Immunopr.cipitation indicates that ZAN inter.cts with other.acr.somal pr.teins, pr.acr.sin/acr.sin and sp32 （ACr.P）, also pr.sent in the HMW complexes. Immunodetection of ZAN and pr.acr.sin/acr.sin on sper.atozoa fur.her.indicates that both pr.teins tr.ffic to the sper. head sur.ace dur.ng capacitation wher. the sper. acr.somal matr.x is still intact, and ther.for. they ar. likely involved in the initial sper.-ZP binding step.

关键词： SPEr. CAPACITATION ANDSPEr.-ZONA PELLUCIDAINTEr.CTION- BACKGr.UND ANDCONFUSION IN THE FIELDS