活性氧介導(dǎo)的AKAP1降解在1-NP誘導(dǎo)線粒體分裂增加致睪酮合成障礙中的作用

活性氧介導(dǎo)的AKAP1降解在1-NP誘導(dǎo)線粒體分裂增加致睪酮合成障礙中的作用摘要：睪酮合成是雄性性激素的關(guān)鍵步驟，其異常合成導(dǎo)致男性不育和一系列代謝性疾病。本文探討了活性氧介導(dǎo)的AKAP1降解在1-NP誘導(dǎo)線粒體分裂增加致睪酮合成障礙中的作用。本研究使用大鼠睪丸原代細(xì)胞模型，并利用1-NP模擬典型的污染物表觀遺傳學(xué)調(diào)節(jié)環(huán)境的影響。結(jié)果發(fā)現(xiàn)，1-NP處理的原代睪丸細(xì)胞線粒體增多，導(dǎo)致氧化應(yīng)激和活性氧水平增加。這進(jìn)一步導(dǎo)致了AKAP1的降解，從而破壞了睪酮生物合成的正常進(jìn)程。同時(shí)，本研究還發(fā)現(xiàn)了線粒體5號(hào)基因與AKAP1的互作關(guān)系。因此，本研究深化了我們對(duì)睪酮合成紊亂的動(dòng)力學(xué)和環(huán)境暴露的機(jī)制的認(rèn)識(shí)。

關(guān)鍵詞：睪酮合成；活性氧；AKAP1；1-NP；線粒體分裂

Abstract:Testosteronesynthesisisacriticalstepinmalehormonebiosynthesis,anditsabnormalsynthesisresultsinmaleinfertilityandarangeofmetabolicdiseases.Thisarticleexplorestheroleofreactiveoxygenspecies-mediatedAKAP1degradationinincreasedmitochondrialfission-inducedtestosteronesynthesisdisordersin1-NP.Thisstudyusedarattesticularprimarycellmodelandused1-NPtosimulatetheeffectsoftypicalpollutantsonepigeneticregulationoftheenvironment.Theresultsshowedthattheprimarytesticularcellstreatedwith1-NPincreasedthenumberofmitochondria,resultinginincreasedoxidativestressandreactiveoxygenspecieslevels.ThisfurtherledtothedegradationofAKAP1,disruptingthenormalprocessoftestosteronebiosynthesis.Inaddition,thisstudyalsodiscoveredtheinteractionbetweenmitochondrial5thgeneandAKAP1.Therefore,thisstudydeepensourunderstandingofthedynamicsoftestosteronesynthesisdisordersandthemechanismsofenvironmentalexposure.

Keywords:testosteronesynthesis;reactiveoxygenspecies;AKAP1;1-NP;mitochondrialfissioInrecentyears,theincreaseinenvironmentalexposurehasbecomeamajorconcernforpublichealthduetoitsadverseeffectsonhumanreproductivehealth.Ithasbeenreportedthatexposuretopollutants,suchas1-nitropyrene(1-NP),canleadtodisordersintestosteronesynthesisinmales,whichinturnaffectsmalereproductivehealth.However,theunderlyingmechanismsofhowexposureto1-NPdisruptstestosteronesynthesisremainunclear.

ThestudyconductedbyChenetal.shedslightonthepotentialmechanismofhowenvironmentalexposureaffectstestosteronesynthesis.Thestudydemonstratedthatexposureto1-NPcausedanincreaseinreactiveoxygenspecieslevels,whichresultedinthedegradationofAKAP1,akeyregulatoroftestosteronebiosynthesis.ThedegradationofAKAP1leadstoadisruptionofthenormalprocessoftestosteronesynthesis,whichultimatelyresultsintestosteronesynthesisdisorders.

Furthermore,thestudydiscoveredtheinteractionbetweenmitochondrial5thgeneandAKAP1.Mitochondrialfissionplaysavitalroleintheregulationoftestosteronebiosynthesis,andithasbeensuggestedthatexposureto1-NPdisruptsmitochondrialdynamics.Thestudyshowedthatexposureto1-NPcausedanincreaseinmitochondrialfission,whichfurtherledtoadecreaseintestosteronesynthesis.

Inconclusion,thisstudyprovidesimportantinsightsonthemechanismsofhowenvironmentalexposureaffectstestosteronesynthesis.Thestudyhighlightstheimportanceofreducingenvironmentalexposuretopollutants,suchas1-NP,tosafeguardmalereproductivehealth.FurtherstudiesareneededtofullyunderstandthecomplexmechanismsofhowenvironmentalexposureaffectstestosteronebiosynthesisInadditiontoreducingenvironmentalexposuretopollutants,therearealsootherwaystosupportmalereproductivehealthandtestosteroneproduction.Oneimportantfactorismaintainingahealthydietandlifestyle.Researchhasshownthatadiethighinprocessedfoods,saturatedfats,andsugarcannegativelyimpacttestosteronelevelswhileadietrichinfruits,vegetables,andwholefoodscanpromotetestosteroneproduction.

Exerciseisalsoimportantforsupportingtestosteroneproduction.Studieshavefoundthatresistancetrainingandhigh-intensityintervaltrainingcanincreasetestosteronelevelsinmen.Adequatesleepandstressmanagementarealsoimportantfactorsinsupportingahealthyendocrinesystemandtestosteroneproduction.

Finally,itisimportanttonotethattestosteronesupplementationshouldonlybeconsideredincasesofdiagnosedtestosteronedeficiencyandunderthesupervisionofahealthcareprovider.Themisuseoftestosteronesupplementationcanleadtoserioushealthcomplications,suchasanincreasedriskofheartdiseaseandprostatecancer.

Inconclusion,thestudyontheeffectsof1-NPontestosteronesynthesishighlightstheimportanceofreducingenvironmentalexposuretopollutantsinordertosafeguardmalereproductivehealth.However,therearealsolifestylefactorsthatcansupporthealthytestosteroneproduction.FurtherresearchisneededtofullyunderstandthecomplexmechanismsthatregulatetestosteronebiosynthesisandtodevelopeffectivestrategiesforpromotingmalereproductivehealthTestosteroneisavitalhormonethatplaysacrucialroleinmalereproductivehealth,aswellasoverallphysicalandmentalwellbeing.Lowtestosteronelevelscanleadtoarangeofhealthissues,suchasreducedmusclemass,decreasedbonedensity,erectiledysfunction,andincreasedriskofdepressionandcardiovasculardisease.Althoughagingisanaturalcausefordecliningtestosteronelevelsinmen,environmentalandlifestylefactorscanalsocontributetothisphenomenon.

Oneofthemostconcerningenvironmentalfactorsthataffectmalereproductivehealthisexposuretoendocrine-disruptingchemicals(EDCs),suchasphthalates,bisphenolA(BPA),andpolycyclicaromatichydrocarbons(PAHs).Thesechemicalsarecommonlyfoundinplastics,foodpackaging,personalcareproducts,andairpollution.Theycaninterferewiththebody'shormonalbalanceandnegativelyimpacttheproductionandmetabolismoftestosterone.

StudieshavefoundthatexposuretoEDCs,particularlyduringcriticalperiodsofdevelopmentsuchasgestationandpuberty,canleadtoimpairedspermatogenesis,reducedtesticularvolume,andalteredspermqualityandmotility.Inaddition,EDCscanalsoinhibittheproductionofkeyenzymesandtransportersinvolvedintestosteronesynthesis,suchascytochromeP450aromataseandsteroidogenicacuteregulatoryprotein(StAR).

Forexample,onestudyinvestigatedtheeffectsofexposureto1-Nitropyrene(1-NP),acommonPAH,ontestosteronesynthesisinratLeydigcells.Theresultsshowedthat1-NPexposuresignificantlydecreasedtheexpressionofStARandothersteroidogenicgenes,leadingtodecreasedtestosteroneproduction.ThissuggeststhatexposuretoairpollutioncontainingPAHscouldpotentiallyinhibittestosteronebiosynthesisinhumansaswell.

InadditiontoreducingexposuretoEDCs,thereareseverallifestylefactorsthatcansupporthealthytestosteroneproduction.Theseincludemaintainingahealthyweight,adoptingabalancedandnutrient-richdiet,engaginginregularexercise,managingstressandgettingsufficientsleep.

Studieshaveshownthatoverweightandobesemenhavelowertestosteronelevelsthantheirleancounterparts,andlosingweightcanhelpincreasetestosteroneproduction.Eatingadietrichinzinc,vitaminD,magnesium,andothermicronutrientsthatareessentialfortestosteronesynthesis,canalsosupporthealthytestosteronelevels.Engaginginstrengthtrainingandhigh-intensityintervaltraining(HIIT)canstimulatetestosteroneproduction,whilechronicstressandsleepdeprivationcanlowertestosteronelevels.

Inconclusion,environmentalandlifestylefactorscangreatlyinfluencemalereproductivehealthandtestosteronelev