Vacuolar‐ATPase isoform a2 regulates macrophages and cytokine profile necessary for normal spermatogenesis in testis

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: pregnancy loss;    Tgf‐;    β;    Nos2;    a2NTD;   

DOI  :  10.1189/jlb.3A1113-593RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

a2Visrequiredformaturationofsperm.Thedecreasedexpressionofa2Vatthefeto‐maternalinterphasecausespoorpregnancyoutcome.Thepresentstudyexaminedtheroleofa2Vinspermatogenesisandinflammatorynetworkinthetestis.Asingledoseofanti‐a2VmouseIgGormouseIgGisotype(3μg/animal)wasinjectedi.p.intomalemiceonalternatedaysfor10days.Anti‐a2V‐treatedmalesexhibitseveredeficienciesofspermatogenesis,whichisindicatedbythepresenceoflessnumbersofpostmeioticcells.Spermcountsandspermmotilitywerereducedsignificantlyinanti‐a2V‐treatedmales.Thereleaseofthecleaveda2NTDwassignificantlylowerinanti‐a2V‐treatedtestes.TheTMswereidentifiedasM2‐likemacrophages,andthispopulationandtheexpressionofvariouscytokines/chemokines(Tgf‐β,Il‐6,Nos2,Tnf,Lif,Mcp1,Ccl5)weredecreasedsignificantlyinanti‐a2V‐treatedtestiscomparedwithcontroltestis.Moreover,thecleaveda2NTDactsasakeymediatorofTMsandsignificantlyup‐regulatesthesecretionoftesticularcytokines/chemokines,whichareassociatedwithnormalspermatogenesis.Whentheseanti‐a2V‐treatedmaleswereusedformatingwithnormalfemales,thenumberofimplantationsiteswasdecreasedsignificantlyinthefemalesmatedwithanti‐a2V‐treatedmalesthanthefemalesmatedwithcontrolmales.Theseobservationssuggestthata2Vplaysacrucialroleinspermatogenesisbyregulatingtesticularimmuneresponses,anditsinhibitioninmalesleadstopoorpregnancyoutcomeinfemales...

【 授权许可】

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