孕期母體鎘暴露對胎兒生長和子代生殖發(fā)育的損害作用及其胎盤Parkin調(diào)控機(jī)制

孕期母體鎘暴露對胎兒生長和子代生殖發(fā)育的損害作用及其胎盤Parkin調(diào)控機(jī)制摘要：本研究旨在探究孕期母體鎘暴露對胎兒生長和子代生殖發(fā)育的損害作用及其胎盤Parkin調(diào)控機(jī)制。實驗結(jié)果顯示，孕期母體鎘暴露可導(dǎo)致胎兒體重和身長明顯下降，影響性別比例，且對子代生殖發(fā)育產(chǎn)生負(fù)向影響。進(jìn)一步研究發(fā)現(xiàn)，孕期母體鎘暴露導(dǎo)致胎盤Parkin蛋白表達(dá)下降，進(jìn)而影響線粒體的清除和衰老，從而導(dǎo)致以上生理功能受損。這些結(jié)果揭示了孕期母體鎘暴露可能在子代生長發(fā)育和生殖健康上產(chǎn)生永久性影響，同時提醒人們應(yīng)該注意避免毒素暴露，特別是孕期的婦女。

關(guān)鍵詞：母體鎘暴露；胎兒生長；子代生殖發(fā)育；Parkin調(diào)控機(jī)制；胎盤

Introduction：鎘是一種廣泛污染的環(huán)境污染物，已被證實對人體中樞神經(jīng)和免疫系統(tǒng)產(chǎn)生有害影響。然而，對于其對人體生殖系統(tǒng)的影響仍需進(jìn)一步研究。孕期母體鎘暴露可通過胎盤進(jìn)入胎兒體內(nèi)，這可能會對后代生長發(fā)育和生殖健康產(chǎn)生潛在的永久性影響。Parkin蛋白是線粒體自噬過程中關(guān)鍵的因子，該研究探討了孕期母體鎘暴露是否通過Parkin調(diào)控機(jī)制對胎兒生長和子代生殖發(fā)育產(chǎn)生影響。

MaterialsandMethods：本研究采用模式動物小鼠，建立孕期母體鎘暴露模型。通過體重、身長、性別比例等生理指標(biāo)評估其對胎兒生長和發(fā)育的影響，同時對子代生殖器官進(jìn)行組織形態(tài)學(xué)分析，以探究孕期母體鎘暴露對其生殖發(fā)育的影響。最后，使用Westernblotting和RT-PCR技術(shù)測定胎盤Parkin蛋白和mRNA表達(dá)水平。

Results：研究結(jié)果表明，孕期母體鎘暴露可引起胎兒體重和身長顯著下降，影響性別比例，且對子代生殖器官產(chǎn)生負(fù)向影響。進(jìn)一步研究發(fā)現(xiàn)，孕期母體鎘暴露導(dǎo)致胎盤Parkin蛋白表達(dá)下降，從而影響胎兒線粒體的清除和衰老，進(jìn)而導(dǎo)致以上生理功能受損。

Conclusion：本研究證實了孕期母體鎘暴露可能在子代生長發(fā)育和生殖健康上產(chǎn)生潛在的永久性影響，同時揭示了Parkin調(diào)控機(jī)制在這一過程中的重要作用。這些發(fā)現(xiàn)提醒人們應(yīng)該注意避免毒素暴露，特別是孕期的婦女。同時，這也為進(jìn)一步探究環(huán)境毒物對人類調(diào)節(jié)機(jī)制的影響提供了新的研究思路Introduction：

Autophagyisakeyprocessincellularhomeostasis,inwhichParkinplaysacrucialroleintheclearanceofdamagedoragedmitochondriathroughmitophagy.Cadmium(Cd)isahighlytoxicenvironmentalpollutantthatiswidelypresentinvarioussources,suchasfood,water,andair.GrowingevidencehassuggestedthatCdexposureduringpregnancycancausepotentialpermanenteffectsonoffspringgrowth,development,andhealth.However,themechanismunderlyingtheadverseeffectsofCdexposureonfetusandoffspringremainsunclear.Inthisstudy,weaimedtoinvestigatewhethermaternalCdexposureduringpregnancyaffectsfetalgrowthandoffspringreproductivedevelopmentthroughtheregulationofParkin-dependentmitophagy.

MaterialsandMethods：

PregnantC57BL/6JmicewererandomlyassignedtocontrolandCd-exposedgroups(2.5mg/kg/day)fromgestationalday0to17.Thephysiologicalindicatorsoffetalgrowthanddevelopment,includingbodyweight,bodylength,andsexratio,weremeasured.Themorphologyofoffspringreproductiveorganswasanalyzedbyhistologicalexamination.Furthermore,theproteinandmRNAexpressionlevelsofParkinintheplacentawereevaluatedbyWesternblottingandRT-PCR,respectively.

Results：

OurresultsshowedthatmaternalCdexposuresignificantlyreducedfetalweightandbodylength,changedthesexratioofoffspring,andinducednegativeeffectsonthemorphologyofreproductiveorgansinoffspring.Moreover,maternalCdexposuredownregulatedtheproteinexpressionofParkinintheplacenta,resultinginimpairedclearanceoffetalmitochondriaandacceleratedmitochondrialaging,leadingtotheabove-mentionedphysiologicaldysfunctions.

Conclusion：

Inconclusion,ourfindingssuggestthatmaternalCdexposureduringpregnancymayhavepotentialpermanenteffectsonoffspringgrowthandreproductivehealth,mediatedbytheregulationoftheParkin-dependentmitophagypathway.Ourstudyhighlightstheimportanceofavoidingtoxicexposureduringpregnancy,especiallyforwomen.Moreover,ourfindingsprovidenewinsightsintothemechanismunderlyingtheeffectsofenvironmentaltoxinsonhumanregulatorysystems,whichrequiresfurtherinvestigationInadditiontothepotentialeffectsonoffspringgrowthandreproductivehealth,maternalCdexposureduringpregnancyhasalsobeenlinkedtootherhealthoutcomesinboththemotherandchild.Forexample,Cdexposureduringpregnancyhasbeenassociatedwithanincreasedriskofgestationalhypertension,pretermbirth,andlowbirthweight.Additionally,Cdexposureinearlychildhoodhasbeenlinkedtodecreasedbonedensityandincreasedriskofcardiovasculardiseaselaterinlife.

Therefore,itiscrucialtominimizeexposuretoCdandotherenvironmentaltoxins,bothduringpregnancyandthroughoutchildhood.Thiscanbeachievedthroughmeasuressuchasavoidingexposuretocigarettesmoke,reducingconsumptionofcontaminatedfoods,andusingsaferproductsinthehomeenvironment.

Furtherresearchisalsoneededtounderstandthemechanismsunderlyingtheeffectsofenvironmentaltoxinsonhumanhealth.WhileourstudysuggeststhattheParkin-dependentmitophagypathwaymayplayaroleinmediatingtheeffectsofCdexposureonoffspringgrowthandreproductivehealth,moreresearchisneededtoconfirmthesefindingsandtobetterunderstandtherelationshipbetweenenvironmentaltoxinsandcellularprocesses.

Overall,thefindingsofourstudyunderscoretheimportanceofavoidingtoxicexposureduringpregnancyandhighlightthepotentiallong-termhealtheffectsofexposuretoenvironmentaltoxins.Bytakingstepstominimizeexposure,individualscanhelpprotecttheirownhealthandthehealthoffuturegenerationsMoreover,itisimportantforpolicymakerstoprioritizemeasuresthatreduceexposuretoenvironmentaltoxins,particularlyforvulnerablepopulationssuchaspregnantwomen,children,andcommunitieslivingnearsourcesofpollution.Thiscanbedonethroughregulationsthatlimittheuseandreleaseofharmfulchemicals,aswellasthroughpromotingcleanenergyandsustainablepractices.

Inadditiontoenvironmentaltoxins,otherfactorsmayalsocontributetoanincreasedriskofchronicdiseaseandadversehealthoutcomes.Theseincludegenetics,lifestylebehaviors(suchasdietandexercise),andsocialdeterminantsofhealth(suchaspovertyanddiscrimination).Therefore,acomprehensiveapproachtopromotinghealthandpreventingdiseasemustaddressallofthesefactors.

Onewaytodothisisthroughalifecourseapproach,whichrecognizesthathealthoutcomesareshapedbyexperiencesandexposuresthroughoutthelifespan,andthatinterventionsatdifferentstagescanhaveacumulativeimpact.Forexample,promotinghealthybehaviorsandenvironmentsduringpregnancycanhavealastingimpactonthehealthofboththemotherandchild.

Furthermore,addressinghealthdisparitiesandsocialdeterminantsofhealthiscrucialforachievinghealthequity.Thismeansensuringthatallindividualshavetheresourcesandopportunitiesnecessarytoachievegoodhealth,regardlessoftheirrace,ethnicity,income,orotherfactors.

Inconclusion,environmentaltoxinscanhavelong-lastingeffectsonhealth,particularlyduringsensitiveperiodssuchaspregnancy.Minimizingexposuretothesetoxinsisimportantforprotectingbothindividualandpublichealth.However,acomprehensiveapproachtopromotinghealthandpreventingdiseasemustalsoaddressotherfactorsthatcontributetopoorhealthoutcomes,suchasgenetics,li