1.Introductionoffishsexreversal
Fishsexreversalmeansthatfishcanchangetheiroriginalsexundercertainconditions, frommaletofemale,orfromfemaletomale,orhavebothsexesatthesametime.The mechanismandreasonofsexreversalinfisharestillnotcompletelyclear,anditmaybe relatedtofactorssuchasgenetics,environment,andhormones.Therearemanyspeciesof fishthathavenaturalorartificiallyinducedsexreversal,suchaseels,groupers,snappers, andtilapias.Fishsexreversalhascertainsignificanceforaquacultureandresource protection.Itcanimproveyieldandquality,andcanalsoincreasegeneticdiversityand adaptability.
2.Whatisthemechanismoffishsexreversal?
Fishrealizesitsreproductivefunctionanddeterminesitsfinalphenotypebycontrollingthe developmentanddifferentiationofgermcellsInthisprocess,hormoneregulationisan importantlink.Hormoneregulationmainlyincludestwosystems,the hypothalamic-pituitary-gonadalaxis(HPGaxis)andthehypothalamic-pituitary-thyroidaxis (HPTaxis).
TheHPGaxisreferstothesecretionofgonadotropin-releasingfactor(GnRH)bythe hypothalamus,whichstimulatesthesecretionofgonadotropin(GTH)bythepituitarygland, andthenactsonthegonadstopromotethesynthesisandsecretionofestrogenand
hormones,aswellastheproliferationandmaturationofgermcells.Estrogenfeedback regulatestheactivityofhypothalamusandpituitarygland,formingadynamicbalance.
TheHPTaxisreferstothesecretionofthyrotropin-releasingfactor(TRH)bythe hypothalamus,whichstimulatesthesecretionofthyroid-stimulatinghormone(TSH)bythe pituitarygland,whichinturnactsonthethyroidgland,promotesthesynthesisand secretionofthyroidhormones,andregulatessystemicmetabolism.Thyroidhormone feedbackregulatestheactivityofhypothalamusandpituitarygland,formingadynamic balance. Whenfishencounterfactorsthatinducesexreversal,theabovetwosystemswillchange, causingtheoriginalmale-femalebalancetobebroken,whichwilltriggeraseriesofgene expression,cellproliferation,tissueremodelingandotherprocesses,andfinallyachievesex change
(1)Whenafishreversesfrommaletofemale,itmaygothroughthefollowingsteps:
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①Degenerationofmalecharacteristics:testisbegantoshrink,spermproduction decreasedorstopped,testicularstromalcellsdecreasedordisappeared,andtestosterone levelsdecreased.
②Inductionoffemalecharacteristics:ovarianprimordiabegintoincrease,oocytesbegin toproliferateorrejuvenate,ovarianstromalcellsbegintoappearorincrease,andestradiol levelsincrease.
③Stablefemalecharacteristics:fullydevelopedovaries,normalovulation,ovulationcycle establishment,stableestradiollevels,etc.
(2)Whenafishreversesfromfemaletomale,itmaygothroughseveralsteps:
①Regressionoffemalecharacteristics:ovariesbegintoshrink,oocytesbegintodecrease ordegenerate,ovarianstromalcellsdecreaseordisappear,andestradiollevelsdecrease, etc.
②Inductionofmalecharacteristics:testicularprimordiabegintoincrease,spermatogonia begintoproliferateorrejuvenate,testicularstromalcellsbegintoappearorincrease,and testosteronelevelsincrease.
③Stablemalecharacteristics:fullydevelopedtestes,normalspermproduction,mating behavior,stabletestosteronelevels,etc.
3.Whyneedtoreversefishsex?
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Thepurposeoffishsexchangeismainlytomaximizethereproductionofoffspringandto enableindividualstoobtainthestimulationofthesex.Andwhyamongvertebrates,only fishundergosexchange?Expertsbelievethattheincreasingdifferentiationamong individualsofhighervertebratesledtothisphenomenon.Nowsciencehasprovedthat exogenoushormonescanalsodenaturefishthatcannotbedenatured.Whetheritislarvae oradultfish,afterpropertreatment,monophyleticorprimarymonophyleticpopulations canbeobtained.Malefisharegenerallyheavierandgrowfasterthanfemalefish.
Therefore,inordertoensurethesupplyoffishmeattothegreatestextent,peopleusesex controltechnologytoincreasetheyieldandvarietyoffishunderthepremiseofensuring thatexogenoushormonesareharmlesstothehumanbody.
4.Howtoreversefishsex?
Themainmeanstoachievefishsexreversalareasfollows:
Exogenoushormoneinduction:Byinjectingorimplantingmaleorfemalehormonesinto fish,thegonadsoffishwillchange,therebychangingtheirsex.Thismethodcanartificially controlthesexratioandreproductivecycleoffishandimprovetheefficiencyof farming.Thecommonexogenoushormonesare17-MethyltestosteroneandLetrozole.
Influenceofenvironmentalfactors:Bychangingthetemperature,light,density,nutrition andotherconditionsoffishlife,itaffectsthehormonelevelandgeneexpressioninthefish, therebyinducingitssexreversal.Thismethodismorenatural,butlesscontrollableand predictable.
Genemanipulation:byeditingortransferringthechromosomesorgenesoffish,making themhavespecificsex-determininggenesormissingsomekeygenes,soastorealizetheir sexreversal.Thisapproachcancreatenewstrainsandtraits,butistechnicallydifficultand mayhavesafetyandethicalconcerns.
5.Whatinfluencedthefishsexreversal?
Thegeneticsexdeterminationmechanismmeansthatthesexdifferentiationdirectionof animalsisnotaffectedbyexternalenvironmentalfactors,andisdeterminedbythegenetic genesonthesexchromosomes.Thesex-determininggeneitselfdoesnotparticipateinthe differentiationofsex,butcanonlycontrolits“determinationprocess”andinitiateaseries ofsexdifferentiationevents.Thegeneticsexdeterminationprocessisaseriesofcomplex
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biochemicalprocessesinteracting,whichultimatelyleadtothedeterminationand differentiationofsexcells.Somecomponentsorcombinationsofcomponentsinthe pathwaymaybecomethedominantfactorsaffectingthedirectionofsexdetermination.
(2)Temperature
Duringthehatchingprocessoffisheggs,therewillbeaspecialperiodcalledthe temperaturesensitiveperiod(temperaturesensitiveperiod,TSP).Duringthetemperature sensitiveperiod,artificiallyraisingorloweringthetemperaturecanignoretheinfluenceof geneticfactorstochangethedirectionofsexdifferentiationandsexratio.Thereareeven genderreversals.Forexample,Niletilapiaentersatemperature-sensitiveperiod9days afterfertilizationDuringthisperiod,acertainproportionofhereditaryfemaleswillrevert tophysiologicalmalesiftreatedatahightemperatureof36°CVASAimmunohistochemical stainingshowedthatthegonadsofNiletilapiatreatedwithhightemperaturechanged fromovariantypetotesticulartypeat21-39daysafterfertilization;thegonadsof hereditaryfemalestreatedwithhightemperatureat99daysafterfertilizationchangedinto truetestes.
(3)Genoushormones
Fishsexhasstrongplasticity,andartificiallychangingtheexternalenvironmentcanalso reversethesexoffishphenotype.Therearetwomainmethodsofartificiallyinducingsex reversalinfish,oneisaddingexogenoushormonestodirectlychangehormonelevelsto inducesexreversal.Commondrugsinclude17-methyltestosterone((17-MT),
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11-ketotestosterone(11-KT),17-estradiol(E2),etc.Thesecondistoaddinhibitordrugsto interferewithhormonesandreceptorsinthebodyincombination,reducetheleveloffish sexhormones,suchasaromataseinhibitorsandsoon.
6.Whatarethecommonlyusedhormonesforfishsexreversal?
(1)17-Methyltestosteronepowder?
Whatis17-Methyltestosteronepowder
17-Methyltestosteronealsoknownas17-alpha-Methyltestosterone,17a-MT,methyltestor as17α-methylandrost-4-en-17β-ol-3-one,isasynthetic,orallyactiveandrogenic-anabolic steroid(AAS)and17α-methylatedderivativeoftestosteronethatisusedtotreatmaleswith androgendeficiency.Itbearsclosestructuralsimilaritytotestosterone,buthasamethyl groupattheC17αpositioninordertoincreaseoralbioavailability.Duetoefficient aromatizationintothepotentestrogenmethylestradiol,17-MethyltestosteronePowderhas relativelyhighestrogenicityandhencepotentialsideeffectssuchasgynecomastia.
Whatis17-Methyltestosteronepowderusedfor?
①Medicaluse:17alpha-MethyltestosteronePowderisorhasbeenusedinthetreatment ofdelayedpuberty,hypogonadism,cryptorchidism,anderectiledysfunctioninmales,and inlowdosestotreatmenopausalsymptoms(specificallyforosteoporosis,hotflashes,and toincreaselibidoandenergy),postpartumbreastpainandengorgement,andbreastcancer inwomen.
②Non-medicaluse:MethyltestosteronePowderisusedforphysiqueand performance-enhancingpurposesbycompetitiveathletes,bodybuilders,andpowerlifters, althoughitisnotcommonlyusedrelativetootherAASforsuchpurposes.
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③Aquacultureuse:MT(17α-Methyltestosterone)isacommonlyusedexogenous androgen.Studieshaveshownthat100%maleratecanbeobtainedbyusing50ug/gMTto treatfemaleOreochromisniloticus;using400ug/mlofMTtotreathatchingOncorhynchus tshawytschacanget100%malerate;fertilizedCyprinuscarpioweretreatedwith5ug/mlof MTsoakingmethodfor75hoursandthenfedwith50mg/kgofMTeverydayfor40to70 days,and100%maleoffspringcouldbeobtained.
(2)Letrozolepowder
WhatisLetrozolepowder?
LetrozolePowderisananti-estrogenandoneofthemostpotentAromataseInhibitorItis commonlysoldunderthebrandnameFemaraamongothersNowItisusedbymany bodybuildersduringpostcycletherapy(PCT)andcomplementsotheranabolicsteroidsor prohormones.LetrozolePowderhelpsthebodygetbacktoitsnormalstageandstabilize thehormonallevels.
WhatisLetrozolepowderusedfor?
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①Treatingbreastcancer:LetrozolePowderisamedicineusedfortreatingbreastcancer.It canalsohelppreventbreastcancercomingback.Itismainlyprescribedforwomenwho havebeenthroughthemenopauseandhaveatypeofcancercalled“hormone-dependent” breastcancer
②InduceandIncreaseOvulation:LetrozolePowderencouragestheovariestoovulateby producingmorenaturalstimulationFemaraPowderimprovesovulationbyblocking estrogenproduction,whichcausesthebodytoreleasehigherthannormallevelsof follicle-stimulatinghormone(FSH).TheadditionallevelsofFSHstimulateovarianfollicle(s) todevelopandmatureintheovary.Forwomenwhodon’tovulateregularlyorwhohave PolycysticOvarianSyndrome(PCOS),theincreasedamountsofFSHcanhelptoproduce maturefollicle(s)andegg(s),soovulationcanoccur.
③Achievingfishsexreversal:Studieshaveshownthataromataseisakeyenzymeinvolved intheregulationoffishsexdifferentiation,andthesexdeterminationoffishcanbe changedbyregulatingtheexpressionofaromatase.Aromataseinhibitors(AI)canreduce theactivityofaromatase,blockthepathwayoftestosteroneandothermalehormonesinto estrogens,andchangetheratioofmalehormonestoestrogensinthebody,thereby inducingmasculinizationoffish.Letrozole(LZ)isacommonlyusedaromataseinhibitor, whichcanachievesexcontroloffishbyinhibitingaromataseactivity,andhasimportant applicationvalueinaquaculture.
17-Methyltestosteroneandletrozolecanbesoldindifferentforms,forexample,raw materials,tablets,pills,etc.Currently,therearemanymanufacturersandsuppliers
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supplying17-methyltestosteroneandLetrozole,butthe17-methyltestosteroneand letrozoletheysellareindifferentforms.Herearesomeinformationofthemanufacturer andsupplierof17-Methyltestosteroneandletrozoleforyourreference.
①AdvaCare:adifferentkindofpharmaceuticalandhealthcareproductscompany.AdvaCare canprovide17-Alpha-MethyltestosteroneandLetrozoletablets.ThedoseofMTis5mg,and thespecificationis10tabletsperbox;thedoseofletrozoleis2.5mg,andthespecificationis10 tabletsperbox.
③KabirLifeSciences:awell-knownplatformforobtaininghigh-qualitypharmaceutical productsthroughavarietyofservices,suchaspharmaceuticalmanufacturing,PCD franchise,andexportingtheirproductsinternationally.Theycanprovide 17-MethyltestosteroneandLetrozoleintablets,theexactspecificationscanbefoundonthe order.
*Precaution:Itisimportanttonotethattheuseandsaleofthesesubstancesisheavily regulated,andobtainingthemwithoutavalidprescriptionisillegalandpotentially dangerous.Individualsseekingtouse17-methyltestosteroneandletrozoleformedical purposesshouldconsultalicensedhealthcareprofessionalwhocanprovideguidanceon theappropriateuseandsourcesofthesedrugs.Itisimportanttofollowallsafetyandlegal guidelinestoavoidpotentiallyharmfulconsequences.
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【Reference】
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[2]WeilSJ,VendolaK,ZhouJ,AdesanyaOO,WangJ,OkaforJ,etal.AndrogenReceptor GeneExpressioninthePrimateOvary:CellularLocalization,Regulation,andFunctional CorrelationsJClinEndocrinolMetab(1998)83:2479–85doi:101210/jcem8374917
[3]Cytogenetictoxicityandgonadaleffectsof17α-methyltestosteroneinAstyanax bimaculatus(Characidae)andOreochromisniloticus(Cichlidae).
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[4]FranksS,AdamsJ,MasonH,PolsonD.OvulatoryDisordersinWomenWithPolycystic OvarySyndrome.ClinObstetGynaecol(1985)12:605–32.doi: 10.1016/S0306-3356(21)00138-2
[5]LackofgenotoxicityinAstyanaxbimaculatusandOreochromisniloticusof 17α-methyltestosteroneusedinfishhatcheriestoproducemalemonosex populations.Rivero-WendtCL,Miranda-VilelaAL,FerreiraMF,AmorimFS,daSilvaVA, LouvandiniH,GrisoliaCK.GenetMolRes.2013Oct24;12(4):5013-22.doi: 10.4238/2013.October.24.14.PMID:24301763
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