【肥胖對(duì)女性生殖的影響文獻(xiàn)綜述6800字】

肥胖對(duì)女性生殖的影響文獻(xiàn)綜述目錄TOC\o"1-2"\h\u13600肥胖對(duì)女性生殖的影響文獻(xiàn)綜述 1282971.肥胖導(dǎo)致女性生殖功能紊亂的可能機(jī)制 112797(1)高瘦素血癥 28586（2）胰島素抵抗(IR)和高雄激素血癥(HA) 219035(3)性激素結(jié)合蛋白(SHBG)與性激素活性改變 2148282.肥胖會(huì)引起慢性炎癥、氧化應(yīng)激 2317093.多囊卵巢綜合征(PCOS)的代謝與卵巢表型 3225414.對(duì)卵巢功能的影響 486125.對(duì)卵母細(xì)胞質(zhì)量的影響 476456.對(duì)胚胎的影響 510017.對(duì)子宮內(nèi)膜的影響 5206238.對(duì)女性妊娠結(jié)局的影響 53639.展望 612507參考文獻(xiàn) 7肥胖已經(jīng)從一個(gè)重大健康風(fēng)險(xiǎn)發(fā)展成為一種流行病。針對(duì)亞洲人口肥胖的定義是身體質(zhì)量指數(shù)（BodyMassIndex,BMI）＞28kg/m2。針對(duì)多囊卵巢綜合征（PCOS）患者其肥胖的標(biāo)準(zhǔn)指體重指數(shù)BMI≥25kg/m2，肥胖的特點(diǎn)是脂肪組織和其他代謝器官的脂質(zhì)儲(chǔ)存增加，導(dǎo)致細(xì)胞質(zhì)毒性、炎癥和氧化應(yīng)激。其結(jié)果使代謝功能紊亂，如II型糖尿病、心血管疾病，最終導(dǎo)致生活質(zhì)量下降。重要的是，到2030年，肥胖和超重成年人的比例預(yù)計(jì)將上升到30%。女性肥胖不僅影響新陳代謝，還影響生殖健康，與同年齡段的體重正常女性相比，肥胖女性排卵功能低下及無排卵性不孕的風(fēng)險(xiǎn)更高ADDINZOTERO_ITEMCSL_CITATION{"citationID":"bp7tehh2","properties":{"formattedCitation":"{\\rtf\\super[1]\\nosupersub{}}","plainCitation":"[1]"},"citationItems":[{"id":284,"uris":["/users/local/Yxii24Rh/items/S445VKBC"],"uri":["/users/local/Yxii24Rh/items/S445VKBC"],"itemData":{"id":284,"type":"article-journal","title":"RecurrentIVFfailure:otherfactors","container-title":"FertilityandSterility","page":"1033-1038","volume":"97","issue":"5","source":"PubMed","abstract":"IVFfailureisaproblemforacoupleinthesingularbutcanbeatragedyintheplural.RecurrentIVFfailurehasmultipleknowncausesbutmanywhicharenotroutinelyconsideredaspartoftheposttreatmentanalysis.Thereasonisthereareseveralcausesassociatedwithlifestyleandothercausesrelatedtopre-existingconditionsthathaveonlyatenuousornoapparentconnectiontofertility.Thisarticleexaminestheimpactofobesity,cigarettesmoke,uterineanatomy,bodymassindex,thyroiddysfunction,immunefactors,thehereditaryandacquiredthrombophilias,andembryotransfertechniqueonrecurrentIVFfailure.","DOI":"10.1016/j.fertnstert.2012.03.017","ISSN":"1556-5653","note":"PMID:22464759","shortTitle":"RecurrentIVFfailure","journalAbbreviation":"Fertil.Steril.","language":"eng","author":[{"family":"Penzias","given":"AlanS."}],"issued":{"date-parts":[["2012",5]]},"PMID":"22464759"}}],"schema":"/citation-style-language/schema/raw/master/csl-citation.json"}[1]。雖然通過促排卵治療可以克服無排卵性不孕，但與體重正常女性相比，肥胖女性對(duì)促性腺激素的反應(yīng)性降低，此種情況下，會(huì)導(dǎo)致卵母細(xì)胞的一個(gè)回收下降，進(jìn)而導(dǎo)致其細(xì)胞質(zhì)量也會(huì)出現(xiàn)一定程度的下降，另外還會(huì)增加著床前胚胎發(fā)育異常的一個(gè)風(fēng)險(xiǎn)，導(dǎo)致可能出現(xiàn)一定程度的流程ADDINZOTERO_ITEMCSL_CITATION{"citationID":"1fq1v9374h","properties":{"formattedCitation":"{\\rtf\\super[2]\\nosupersub{}}","plainCitation":"[2]"},"citationItems":[{"id":286,"uris":["/users/local/Yxii24Rh/items/EGSK783W"],"uri":["/users/local/Yxii24Rh/items/EGSK783W"],"itemData":{"id":286,"type":"article-journal","title":"Obesityandreproductivefunction:areviewoftheevidence","container-title":"CurrentOpinioninObstetrics&Gynecology","page":"455-460","volume":"26","issue":"6","source":"PubMed","abstract":"PURPOSEOFREVIEW:Overthelastdecade,theevidencelinkingobesitytoimpairedreproductivefunctionhasgrown.Inthisarticle,wereviewthisevidenceanddiscusstheunderlyingpathophysiology.\nRECENTFINDINGS:Obesewomenarelesslikelythannormal-weightwomentoachievepregnancy.Femaleobesityadverselyaffectsreproductivefunctionthroughalterationsinthehypothalamic-pituitary-ovarianaxis,oocytequality,andendometrialreceptivity.Itisunclearwhichmechanismcontributesthemosttosubfecundity,anditislikelyacumulativeprocess.Emergingdatahighlightthecontributionofmaleobesitytoimpairedreproductivefunctionandthatcoupleobesityhassynergisticadverseeffects.Oncepregnant,obesewomenareathigherriskforadversepregnancyoutcomes.Weightlossimprovesreproductivepotentialinobesepatients.Asobesewomensurpass35yearsofage,agemaybemoreimportantthanbodymassindexindeterminingreproductivepotential.\nSUMMARY:Obstetriciangynecologistsneedtobeawareofthenegativeimpactofobesityonreproductivefunctionsothattheyappropriatelycounseltheirpatients.Furtherworkisneededtoclarifytheunderlyingpathophysiologyresponsibleforadverseeffectsofobesityonreproductionsothatnoveltreatmentapproachesmaybedeveloped.","DOI":"10.1097/GCO.0000000000000113","ISSN":"1473-656X","note":"PMID:25254319","shortTitle":"Obesityandreproductivefunction","journalAbbreviation":"Curr.Opin.Obstet.Gynecol.","language":"eng","author":[{"family":"Klenov","given":"VioletE."},{"family":"Jungheim","given":"EmilyS."}],"issued":{"date-parts":[["2014",12]]},"PMID":"25254319"}}],"schema":"/citation-style-language/schema/raw/master/csl-citation.json"}[2]，因此目前研究熱點(diǎn)在于如何逆轉(zhuǎn)肥胖女性不孕。1.肥胖導(dǎo)致女性生殖功能紊亂的可能機(jī)制肥胖是由于人體內(nèi)的脂肪堆積導(dǎo)致的，而人體內(nèi)的脂肪組織可以分為兩種，一種是白色脂肪，另一種是棕色脂肪，這兩種脂肪在人體的分布具有一定的區(qū)域性，從目前的研究來看，白色的脂肪組織主要分布在一些具有活躍的內(nèi)分泌、自分泌、以及旁分泌的組織器官中，在激素分泌方面，其能夠分泌一些瘦素、脂聯(lián)素以及相關(guān)的因子或者白介素等多方面，而這些激素與細(xì)胞因子能夠干擾女性的生殖系統(tǒng)，肥胖患者能夠通過這些組織來分泌這些激素，關(guān)于肥胖影響其機(jī)制，可能存在以下幾種機(jī)制。(1)高瘦素血癥瘦素(leptin)作為肥胖基因的蛋白產(chǎn)物，其能夠與受體結(jié)合進(jìn)而發(fā)揮其對(duì)應(yīng)的作用，而這種受體主要存在于人的下丘腦、大腦、肝臟、腎、心肺等組織內(nèi)。其在影響下丘腦以及相關(guān)影響物質(zhì)方面有著橋梁作用，并且在女性的青春期的發(fā)展中有著重要的作用，這種作用主要是由于瘦素達(dá)到一定水平后，其青春期才能更好的發(fā)展。在肥胖患者中，瘦素水平是處于一個(gè)升高的狀態(tài)，歸結(jié)原因在于肥胖患者會(huì)存在瘦素抵抗現(xiàn)象，當(dāng)肥胖患者體內(nèi)瘦素升高之初，其體內(nèi)的下丘腦神經(jīng)肽也會(huì)對(duì)應(yīng)的增加，而這種神經(jīng)肽的增加則會(huì)影響GnRH的分泌，并且這種影響呈現(xiàn)一個(gè)抑制作用，另外對(duì)于處于升高的瘦素還能夠直接對(duì)下丘腦的GnRH達(dá)到一個(gè)抑制作用，我們可以認(rèn)為這可能就是肥胖患者體內(nèi)會(huì)出現(xiàn)瘦素后，導(dǎo)致其在體內(nèi)的一個(gè)內(nèi)分泌系統(tǒng)的紊亂[3,4]。另有研究指出這種瘦素能夠?qū)︻w粒細(xì)胞以及卵泡細(xì)胞或者類固醇的合成過程起到抑制作用，也可通過從下游手段方面，通過瘦素的一個(gè)生成因子，反向影響從而對(duì)卵巢功能起到一個(gè)抑制作用。（2）胰島素抵抗(IR)和高雄激素血癥(HA)肥胖患者能夠?qū)е麦w內(nèi)的一個(gè)胰島素敏感性的下降，主要是由于在其能夠影響胰島素的受體密度，這樣一來，就會(huì)導(dǎo)致患者出現(xiàn)胰島素抵抗的現(xiàn)象。另外通過相關(guān)的動(dòng)物實(shí)驗(yàn)證明，瘦素對(duì)于胰島素在體內(nèi)的一個(gè)轉(zhuǎn)運(yùn)過程起到一個(gè)抑制或者削弱的作用，以上過程均證明分肥胖在對(duì)于胰島素抵抗有促進(jìn)作用，但是這個(gè)不良影響則會(huì)導(dǎo)致患者出現(xiàn)高胰島素血癥。從現(xiàn)有的知識(shí)體系來理解高胰島素血癥又會(huì)刺激卵巢以及腎上腺素的一個(gè)合成作用，而其實(shí)際的影響機(jī)制可能是胰島素能夠增加LH受體數(shù)目并且其能通過對(duì)應(yīng)的酶來刺激腎上腺素的一個(gè)分泌；另外過量的胰島素還能夠促進(jìn)卵巢濾泡囊腫的生成過程，進(jìn)而影響相關(guān)激素的分泌，最終的一個(gè)結(jié)果就是卵泡閉鎖或者無排卵的一個(gè)情況出現(xiàn)[5,6]。(3)性激素結(jié)合蛋白(SHBG)與性激素活性改變談到SHBG方面名主要是在肥胖患者的血液循環(huán)中，其含量降低，且這種蛋白是水平的降低還能夠與血胰島素、雄激素、以及胰島素生長因子之間的濃度呈現(xiàn)一個(gè)負(fù)相關(guān)。當(dāng)雄激素與胰島素水平增高時(shí)，其主要是通過對(duì)肝臟的一個(gè)作用，來達(dá)到降低SHBG的分泌。作為性激素的一個(gè)載體，SHBG對(duì)于雄激素以及E2的一個(gè)生物活性方面均有重要的影響，甚至可以說是一個(gè)決定性因素。在正常情況下，女性的百分之八十的睪酮能夠與性激素結(jié)合蛋白結(jié)合，而在雌二醇中，有38%的含量同樣與相關(guān)蛋白結(jié)合。在肥胖患者的體內(nèi)，這種結(jié)合蛋白是處于一個(gè)較低水平，此時(shí)雄激素和雌二醇的生物利用度則會(huì)出現(xiàn)不同程度的一個(gè)上升過程，這種有效的上升過程，能夠?qū)ο虑鹉X垂體軸產(chǎn)生抑制作用，因此會(huì)導(dǎo)致高雄激素體征的出現(xiàn)[7]。2.肥胖會(huì)引起慢性炎癥、氧化應(yīng)激慢性炎癥的定義是不受控制的和持續(xù)的趨化因子和細(xì)胞因子的合成和分泌。這可能是由于組織損傷后未解決的炎癥引起的ADDINZOTERO_ITEMCSL_CITATION{"citationID":"1fq1v9374h","properties":{"formattedCitation":"{\\rtf\\super[2]\\nosupersub{}}","plainCitation":"[2]"},"citationItems":[{"id":286,"uris":["/users/local/Yxii24Rh/items/EGSK783W"],"uri":["/users/local/Yxii24Rh/items/EGSK783W"],"itemData":{"id":286,"type":"article-journal","title":"Obesityandreproductivefunction:areviewoftheevidence","container-title":"CurrentOpinioninObstetrics&Gynecology","page":"455-460","volume":"26","issue":"6","source":"PubMed","abstract":"PURPOSEOFREVIEW:Overthelastdecade,theevidencelinkingobesitytoimpairedreproductivefunctionhasgrown.Inthisarticle,wereviewthisevidenceanddiscusstheunderlyingpathophysiology.\nRECENTFINDINGS:Obesewomenarelesslikelythannormal-weightwomentoachievepregnancy.Femaleobesityadverselyaffectsreproductivefunctionthroughalterationsinthehypothalamic-pituitary-ovarianaxis,oocytequality,andendometrialreceptivity.Itisunclearwhichmechanismcontributesthemosttosubfecundity,anditislikelyacumulativeprocess.Emergingdatahighlightthecontributionofmaleobesitytoimpairedreproductivefunctionandthatcoupleobesityhassynergisticadverseeffects.Oncepregnant,obesewomenareathigherriskforadversepregnancyoutcomes.Weightlossimprovesreproductivepotentialinobesepatients.Asobesewomensurpass35yearsofage,agemaybemoreimportantthanbodymassindexindeterminingreproductivepotential.\nSUMMARY:Obstetriciangynecologistsneedtobeawareofthenegativeimpactofobesityonreproductivefunctionsothattheyappropriatelycounseltheirpatients.Furtherworkisneededtoclarifytheunderlyingpathophysiologyresponsibleforadverseeffectsofobesityonreproductionsothatnoveltreatmentapproachesmaybedeveloped.","DOI":"10.1097/GCO.0000000000000113","ISSN":"1473-656X","note":"PMID:25254319","shortTitle":"Obesityandreproductivefunction","journalAbbreviation":"Curr.Opin.Obstet.Gynecol.","language":"eng","author":[{"family":"Klenov","given":"VioletE."},{"family":"Jungheim","given":"EmilyS."}],"issued":{"date-parts":[["2014",12]]},"PMID":"25254319"}}],"schema":"/citation-style-language/schema/raw/master/csl-citation.json"}[8]。另外，環(huán)境壓力(如過敏原)、代謝異常(如微生物群變化)或組織內(nèi)持續(xù)壞死的細(xì)胞死亡(如肥胖脂肪細(xì)胞)可誘導(dǎo)新生炎癥反應(yīng)ADDINZOTERO_ITEMCSL_CITATION{"citationID":"1fq1v9374h","properties":{"formattedCitation":"{\\rtf\\super[2]\\nosupersub{}}","plainCitation":"[2]"},"citationItems":[{"id":286,"uris":["/users/local/Yxii24Rh/items/EGSK783W"],"uri":["/users/local/Yxii24Rh/items/EGSK783W"],"itemData":{"id":286,"type":"article-journal","title":"Obesityandreproductivefunction:areviewoftheevidence","container-title":"CurrentOpinioninObstetrics&Gynecology","page":"455-460","volume":"26","issue":"6","source":"PubMed","abstract":"PURPOSEOFREVIEW:Overthelastdecade,theevidencelinkingobesitytoimpairedreproductivefunctionhasgrown.Inthisarticle,wereviewthisevidenceanddiscusstheunderlyingpathophysiology.\nRECENTFINDINGS:Obesewomenarelesslikelythannormal-weightwomentoachievepregnancy.Femaleobesityadverselyaffectsreproductivefunctionthroughalterationsinthehypothalamic-pituitary-ovarianaxis,oocytequality,andendometrialreceptivity.Itisunclearwhichmechanismcontributesthemosttosubfecundity,anditislikelyacumulativeprocess.Emergingdatahighlightthecontributionofmaleobesitytoimpairedreproductivefunctionandthatcoupleobesityhassynergisticadverseeffects.Oncepregnant,obesewomenareathigherriskforadversepregnancyoutcomes.Weightlossimprovesreproductivepotentialinobesepatients.Asobesewomensurpass35yearsofage,agemaybemoreimportantthanbodymassindexindeterminingreproductivepotential.\nSUMMARY:Obstetriciangynecologistsneedtobeawareofthenegativeimpactofobesityonreproductivefunctionsothattheyappropriatelycounseltheirpatients.Furtherworkisneededtoclarifytheunderlyingpathophysiologyresponsibleforadverseeffectsofobesityonreproductionsothatnoveltreatmentapproachesmaybedeveloped.","DOI":"10.1097/GCO.0000000000000113","ISSN":"1473-656X","note":"PMID:25254319","shortTitle":"Obesityandreproductivefunction","journalAbbreviation":"Curr.Opin.Obstet.Gynecol.","language":"eng","author":[{"family":"Klenov","given":"VioletE."},{"family":"Jungheim","given":"EmilyS."}],"issued":{"date-parts":[["2014",12]]},"PMID":"25254319"}}],"schema":"/citation-style-language/schema/raw/master/csl-citation.json"}[9]。肥胖能夠?qū)β涯讣?xì)胞有一個(gè)損傷的過程，探究其機(jī)制主要是其存在一個(gè)脂毒性。通過飲食能夠得到較多的脂肪酸，這種未能及時(shí)消耗掉的脂肪酸會(huì)議甘油三酯的形式存到對(duì)應(yīng)的脂肪細(xì)胞中，在脂肪細(xì)胞中它們似乎不會(huì)引起細(xì)胞損傷[10]。然而，當(dāng)這種能力被持續(xù)的飲食過量所壓倒時(shí)，脂肪酸會(huì)在其他組織中積累并產(chǎn)生毒性作用，這被稱為脂毒性[11]。肥胖患者其血液循環(huán)中過多的甘油三酯儲(chǔ)存在脂肪細(xì)胞中，導(dǎo)致脂肪細(xì)胞肥大，最終因缺氧導(dǎo)致脂肪細(xì)胞壞死并誘導(dǎo)釋放單核細(xì)胞趨化蛋白（MCP-1）和煙酰胺磷酸核糖基轉(zhuǎn)移酶（NAMPT），并在其釋放后募集循環(huán)中的巨噬細(xì)胞和T細(xì)胞向脂肪組織中浸潤。隨后巨噬細(xì)胞分泌促炎細(xì)胞因子并激活NF-kB信號(hào)通路產(chǎn)生更多的促炎細(xì)胞因子。當(dāng)這些過多的促炎細(xì)胞因子進(jìn)入血液循環(huán)中時(shí)，它們會(huì)作用于其它組織中引發(fā)炎癥反應(yīng)，同時(shí)也包含了卵巢組織ADDINZOTERO_ITEMCSL_CITATION{"citationID":"20g5s8aho3","properties":{"formattedCitation":"{\\rtf\\super[6]\\nosupersub{}}","plainCitation":"[6]"},"citationItems":[{"id":294,"uris":["/users/local/Yxii24Rh/items/U5XGWQGA"],"uri":["/users/local/Yxii24Rh/items/U5XGWQGA"],"itemData":{"id":294,"type":"article-journal","title":"Obesity-DependentIncreasesinOocytemRNAsAreAssociatedWithIncreasesinProinflammatorySignalingandGutMicrobialAbundanceofLachnospiraceaeinFemaleMice","container-title":"Endocrinology","page":"1630-1643","volume":"157","issue":"4","source":"PubMed","abstract":"RNAsstoredinthemetaphaseII-arrestedoocyteplayimportantrolesinsuccessfulembryonicdevelopment.TheirabundanceisdefinedbytranscriptionalactivityduringoocytegrowthandselectivedegradationoftranscriptsduringLH-inducedoocytematuration.OurpreviousstudiesdemonstratedthatmRNAabundanceisincreasedinmatureovulatedoocytescollectedfromobesehumansandmiceandthereforemaycontributetoreducedoocytedevelopmentalcompetenceassociatedwithmetabolicdysfunction.Inthecurrentstudymousemodelsofdiet-inducedobesitywereusedtodeterminewhetherobesity-dependentincreasesinproinflammatorysignalingregulateovarianabundanceofoocyte-specificmRNAs.Theabundanceofoocyte-specificBnc1,Dppa3,andPou5f1mRNAsaswellasmarkersofproinflammatorysignalingweresignificantlyincreasedinovariesofobesecomparedwithleanmicewhichweredepletedoffullygrownpreovulatoryfollicles.Chromatin-immunoprecipitationanalysesalsodemonstratedincreasedassociationofphosphorylatedsignaltransducerandactivatoroftranscription3withthePou5f1promoterinovariesofobesemicesuggestingthatproinflammatorysignalingregulatestranscriptionofthisgeneintheoocyte.Thececummicrobialcontentofleanandobesefemalemicewassubsequentlyexaminedtoidentifypotentialrelationshipsbetweenmicrobialcompositionandproinflammatorysignalingintheovary.MultivariateAssociationwithLinearModelsidentifiedsignificantpositivecorrelationsbetweencecumabundanceofthebacterialfamilyLachnospiraceaeandovarianabundanceofTnfaaswellasDppa3,Bnc1,andPou5f1mRNAs.Together,thesedatasuggestthatdiet-inducedchangesingutmicrobialcompositionmaybecontributingtoovarianinflammationwhichinturnaltersovariangeneexpressionandultimatelycontributestoobesity-dependentreductioninoocytequalityanddevelopmentofinfertilityinobesepatients.","DOI":"10.1210/en.2015-1851","ISSN":"1945-7170","note":"PMID:26881311\nPMCID:PMC4816731","journalAbbreviation":"Endocrinology","language":"eng","author":[{"family":"Xie","given":"Fang"},{"family":"Anderson","given":"ChristopherL."},{"family":"Timme","given":"KelseyR."},{"family":"Kurz","given":"ScottG."},{"family":"Fernando","given":"SamodhaC."},{"family":"Wood","given":"JenniferR."}],"issued":{"date-parts":[["2016",4]]},"PMID":"26881311"}}],"schema":"/citation-style-language/schema/raw/master/csl-citation.json"}[12]。另外慢性炎癥會(huì)引起氧化應(yīng)激反應(yīng)，這主要是因?yàn)樵诼匝装Y中產(chǎn)生的活性氧成分較多，其遠(yuǎn)遠(yuǎn)超過了細(xì)胞抗氧化的能力，因此其能夠?qū)е掳l(fā)生一系列的氧化應(yīng)激反應(yīng)。從目前的種類來看，其主要種類有兩種，這兩種都是由多種細(xì)胞器組成，涉及到線粒體、內(nèi)質(zhì)網(wǎng)以及相關(guān)的酶等ADDINZOTERO_ITEMCSL_CITATION{"citationID":"20g5s8aho3","properties":{"formattedCitation":"{\\rtf\\super[6]\\nosupersub{}}","plainCitation":"[6]"},"citationItems":[{"id":294,"uris":["/users/local/Yxii24Rh/items/U5XGWQGA"],"uri":["/users/local/Yxii24Rh/items/U5XGWQGA"],"itemData":{"id":294,"type":"article-journal","title":"Obesity-DependentIncreasesinOocytemRNAsAreAssociatedWithIncreasesinProinflammatorySignalingandGutMicrobialAbundanceofLachnospiraceaeinFemaleMice","container-title":"Endocrinology","page":"1630-1643","volume":"157","issue":"4","source":"PubMed","abstract":"RNAsstoredinthemetaphaseII-arrestedoocyteplayimportantrolesinsuccessfulembryonicdevelopment.TheirabundanceisdefinedbytranscriptionalactivityduringoocytegrowthandselectivedegradationoftranscriptsduringLH-inducedoocytematuration.OurpreviousstudiesdemonstratedthatmRNAabundanceisincreasedinmatureovulatedoocytescollectedfromobesehumansandmiceandthereforemaycontributetoreducedoocytedevelopmentalcompetenceassociatedwithmetabolicdysfunction.Inthecurrentstudymousemodelsofdiet-inducedobesitywereusedtodeterminewhetherobesity-dependentincreasesinproinflammatorysignalingregulateovarianabundanceofoocyte-specificmRNAs.Theabundanceofoocyte-specificBnc1,Dppa3,andPou5f1mRNAsaswellasmarkersofproinflammatorysignalingweresignificantlyincreasedinovariesofobesecomparedwithleanmicewhichweredepletedoffullygrownpreovulatoryfollicles.Chromatin-immunoprecipitationanalysesalsodemonstratedincreasedassociationofphosphorylatedsignaltransducerandactivatoroftranscription3withthePou5f1promoterinovariesofobesemicesuggestingthatproinflammatorysignalingregulatestranscriptionofthisgeneintheoocyte.Thececummicrobialcontentofleanandobesefemalemicewassubsequentlyexaminedtoidentifypotentialrelationshipsbetweenmicrobialcompositionandproinflammatorysignalingintheovary.MultivariateAssociationwithLinearModelsidentifiedsignificantpositivecorrelationsbetweencecumabundanceofthebacterialfamilyLachnospiraceaeandovarianabundanceofTnfaaswellasDppa3,Bnc1,andPou5f1mRNAs.Together,thesedatasuggestthatdiet-inducedchangesingutmicrobialcompositionmaybecontributingtoovarianinflammationwhichinturnaltersovariangeneexpressionandultimatelycontributestoobesity-dependentreductioninoocytequalityanddevelopmentofinfertilityinobesepatients.","DOI":"10.1210/en.2015-1851","ISSN":"1945-7170","note":"PMID:26881311\nPMCID:PMC4816731","journalAbbreviation":"Endocrinology","language":"eng","author":[{"family":"Xie","given":"Fang"},{"family":"Anderson","given":"ChristopherL."},{"family":"Timme","given":"KelseyR."},{"family":"Kurz","given":"ScottG."},{"family":"Fernando","given":"SamodhaC."},{"family":"Wood","given":"JenniferR."}],"issued":{"date-parts":[["2016",4]]},"PMID":"26881311"}}],"schema":"/citation-style-language/schema/raw/master/csl-citation.json"}[13-15]。過多的H2O2可以在細(xì)胞的細(xì)胞質(zhì)與細(xì)胞器之間只有移動(dòng)并通過磷酸化激活NF-kB信號(hào)轉(zhuǎn)到通路產(chǎn)生更多的促炎細(xì)胞因子。基于炎癥和氧化應(yīng)激的這種相互依賴關(guān)系，就可以解釋肥胖也是一種慢性氧化應(yīng)激狀態(tài)[16]。3.多囊卵巢綜合征(PCOS)的代謝與卵巢表型多囊卵巢綜合征（Polycysticovarysyndrome,PCOS）是一種雄激素過多的疾病，RodgersADDINZOTERO_ITEMCSL_CITATION{"citationID":"ohr60ork6","properties":{"formattedCitation":"{\\rtf\\super[28]\\nosupersub{}}","plainCitation":"[28]"},"citationItems":[{"id":340,"uris":["/users/local/Yxii24Rh/items/B8UT9BXR"],"uri":["/users/local/Yxii24Rh/items/B8UT9BXR"],"itemData":{"id":340,"type":"article-journal","title":"Complexdiseasesandco-morbidities:polycysticovarysyndromeandtype2diabetesmellitus","container-title":"EndocrineConnections","source":"PubMed","abstract":"OBJECTIVE:Manycomplexdiseasesexhibitco-morbiditiesoftenrequiringmanagementbymorethanonehealthspecialist.Weexaminedcross-specialityissuesthatultimatelyaffectthehealthandwellbeingofpatientswithpolycysticovarysyndrome(PCOS).PCOSwasoriginallydescribedasareproductiveconditionbutisnowrecognisedtoalsobeametabolicandpsychologicalconditionaffecting8-13%ofwomenofreproductiveage.Withafour-foldincreasedriskoftype2diabetes(DM2),thePopulationAttributableRiskofDM2thatcouldbeavoidedifPCOSwereeliminatedisasubstantial19-28%ofwomenofreproductiveage.TodeterminetheextenttowhichPCOSisanimportantconsiderationindiabetesdevelopmentweexaminedpublications,funding,guidelinesandpredictorsofriskofdevelopingDM2.\nRESULTS:WefoundthetopicofPCOSappearedinspecialistdiabetesjournalsatonly10%therateseeninendocrinologyjournals;about1in500articles.Wefoundresearchfundingtobesubstantiallylessthanfordiabetes,andfoundthatdiabetesguidelinesandpredictivetoolsforDM2riskmostlyignorePCOS.ThisissurprisingsinceinsulinresistanceinwomenwithPCOShasadifferentaetiologyandadditionallywomenwithPCOSareatincreasedriskofbecomingoverweightorobese;highriskfactorsforDM2.\nCONCLUSIONS:Weconsiderthecausesoftheseconcerninganomaliesanddiscusscurrentactivitiestoaddresstheco-morbiditiesofPCOS,includingtherecentdevelopmentofinternationalguidelines,aninternationalPCOSawarenessprogramandpotentiallychangingthenameofPCOStobetterreflectitsmetabolicconsequences.","DOI":"10.1530/EC-18-0502","ISSN":"2049-3614","note":"PMID:30763275\nPMCID:PMC6410761","shortTitle":"Complexdiseasesandco-morbidities","journalAbbreviation":"EndocrConnect","language":"eng","author":[{"family":"Rodgers","given":"Ray"},{"family":"Avery","given":"Jodie"},{"family":"Moore","given":"Vivienne"},{"family":"Davies","given":"Michael"},{"family":"Azziz","given":"Ricardo"},{"family":"Stener-Victorin","given":"Elisabeth"},{"family":"Moran","given":"Lisa"},{"family":"Robertson","given":"Sarah"},{"family":"Stepto","given":"Nigel"},{"family":"Norman","given":"Rob"},{"family":"Teede","given":"HelenaJ."}],"issued":{"date-parts":[["2019",2,1]]},"PMID":"30763275"}}],"schema":"/citation-style-language/schema/raw/master/csl-citation.json"}[17]等研究發(fā)現(xiàn)患有多囊卵巢綜合征的女性患肥胖癥和2型糖尿病的發(fā)病風(fēng)險(xiǎn)是增加的，與沒有多囊卵巢綜合征的肥胖女性的表型相重疊。例如,FuratRencberADDINZOTERO_ITEMCSL_CITATION{"citationID":"6s3a1kf47","properties":{"formattedCitation":"{\\rtf\\super[29]\\nosupersub{}}","plainCitation":"[29]"},"citationItems":[{"id":342,"uris":["/users/local/Yxii24Rh/items/6VQJBWMR"],"uri":["/users/local/Yxii24Rh/items/6VQJBWMR"],"itemData":{"id":342,"type":"article-journal","title":"EffectofresveratrolandmetforminonovarianreserveandultrastructureinPCOS:anexperimentalstudy","container-title":"JournalofOvarianResearch","page":"55","volume":"11","issue":"1","source":"PubMed","abstract":"BACKGROUND:PCOSisareproductivehormonalabnormalityandametabolicdisorder.Itisfrequentlyassociatedwithinsulinresistance,hyperandrogenism,chronicinflammation,andoxidativestress.WeaimtoinvestigatethepotentialtherapeuticeffectsofcombinedtherapyofresveratrolandmetforminonpolycysticovariesviaSIRT1andAMPKactivation.\nMETHODS:Wistaralbinoratsweredividedintocontrolandexperimental(PCOS)groups.DHEA-inducedPCOSratsweregivenresveratrol(20

mg/kg/day),metformin(300

mg/kg/day)andcombinedtherapy.Attheendoftheexperiment,thebodyandovarianweightofratsweremeasuredandbloodsampleswereanalyzedforFSH,LH,testosterone,AMH,TNF-αandMDAlevels.Histopathologicalevaluationofovarieswerecarriedoutbylightandelectronmicroscopy.SIRT1andAMPKimmunreactivityandTUNELassaywerescored.DatawerestatisticallyanalyzedbySPSSprogramme.\nRESULTS:MetforminandcombinedtreatmentgroupsreducedthebodyandovaryweightscomparedtothePCOSgroup.SerumtestosteronelevelsweresignificantlyhigherinthePCOSgroupthaninthecontrolgroupandthiswasreducedwhenPCOSwastreatedwithallbutespeciallyresveratrol.AllthetreatmentgroupsdecreasedLH,LH/FSH,TNF-αandtissueAMHlevelswhichwereinducedinthePCOSgroup,whereasmetforminwasunabletoimprovetheincreasedMDAandplasmaAMHlevels.Treatmentwithresveratroland/ormetforminamelioratedtheelevatednumberofsecondaryandatreticfolliclesandthedecreasednumberofGraafianfolliclesinthePCOSgroup,whichindicatestheeffectofthetreatmentsonthemaintenanceoffolliculogenesis.Lightandelectronmicroscopicfindingssupportedtheanalysisoffollicularcount.IncreasednumberofTUNEL(+)granulosacellsinthePCOSgroupwerereducedsignificantlyinthetreatmentgroups.ResveratrolandmetforminincreasedSIRT1andAMPKimmunreactivity,respectively,comparedtothePCOSgroup.\nCONCLUSIONS:Theresultssuggestthatcombinedtherapyofmetforminandresveratrolmayimprovetheweightgain,hormoneprofileandovarianfollicularcellarchitecturebyinducingantioxidantandantiinflammatorysystemsviaSIRT1andAMPKactivationinPCOS.","DOI":"10.1186/s13048-018-0427-7","ISSN":"1757-2215","note":"PMID:29958542\nPMCID:PMC6025739","shortTitle":"EffectofresveratrolandmetforminonovarianreserveandultrastructureinPCOS","journalAbbreviation":"JOvarianRes","language":"eng","author":[{"family":"FuratRencber","given":"Selenay"},{"family":"KurnazOzbek","given":"Sema"},{"family":"Eraldem?r","given":"Ceyla"},{"family":"Sezer","given":"Zehra"},{"family":"Kum","given":"Tugba"},{"family":"Ceylan","given":"Sureyya"},{"family":"Guzel","given":"Elif"}],"issued":{"date-parts":[["2018",6,29]]},"PMID":"29958542"}}],"schema":"/citation-style-language/schema/raw/master/csl-citation.json"}[18]等在PCOS的鼠模型中研究發(fā)現(xiàn)TNFα、丙二醛以及脂質(zhì)代謝物增加，表明多囊卵巢綜合征患者存在慢性卵巢炎癥和氧化應(yīng)激。而且AlshammariADDINZOTERO_ITEMCSL_CITATION{"citationID":"21r94lvkde","properties":{"formattedCitation":"{\\rtf\\super[30]\\nosupersub{}}","plainCitation":"[30]"},"citationItems":[{"id":344,"uris":["/users/local/Yxii24Rh/items/42DDXNXT"],"uri":["/users/local/Yxii24Rh/items/42DDXNXT"],"itemData":{"id":344,"type":"article-journal","title":"Geneexpressionofinflammatorymarkersinadiposetissuebetweenobesewomenwithpolycysticovaryandnormalobesewomen","container-title":"EuropeanReviewforMedicalandPharmacologicalSciences","page":"1099-1105","volume":"21","issue":"5","source":"PubMed","abstract":"OBJECTIVE:Thepathogenesisofpolycysticovarysyndrome(PCOS),acommonendocrinediseaseandmetabolicdisturbance,isstillunknown.TheaimofthestudywastoinvestigatewhetherpatientswithPCOSdisplayincreasedexpressionofin?ammatorymarkersinadiposetissue.\nPATIENTSANDMETHODS:Twogroupsofwomenwereinvestigated,thosediagnosedwithPCOS(n=8)andageandBMI-matchednormalwomen(n=12).Theiragewasbetween20-45yearsandallsubjectswereapparentlyhealthyanddidnottakeanymedications.AdiposetissuelevelsofmRNAofin?ammatorymarkersweredeterminedbyuseofreal-timePCR.\nRESULTS:TherewerenodifferencesbetweenobesepatientsandobesePCOSinlevelsofadipocytokines.\nCONCLUSIONS:TherewerenoeffectsofPCOSontheexpressionofanyoftheadipocytokinesgenesmeasuredinsubcutaneousadiposetissue.","ISSN":"2284-0729","note":"PMID:28338181","journalAbbreviation":"EurRevMedPharmacolSci","language":"eng","author":[{"family":"Alshammari","given":"G."},{"family":"Khan","given":"R."},{"family":"Brameld","given":"J."},{"family":"Amer","given":"S."},{"family":"Lomax","given":"M.A."}],"issued":{"date-parts":[["2017"]]},"PMID":"28338181"}}],"schema":"/citation-style-language/schema/raw/master/csl-citation.json"}[19]以及ArtimaniADDINZOTERO_ITEMCSL_CITATION{"citationID":"2ahvjcc5r0","properties":{"formattedCitation":"{\\rtf\\super[31]\\nosupersub{}}","plainCitation":"[31]"},"citationItems":[{"id":346,"uris":["/users/local/Yxii24Rh/items/UKMTBMNF"],"uri":["/users/local/Yxii24Rh/items/UKMTBMNF"],"itemData":{"id":346,"type":"article-journal","title":"Evaluationofpro-oxidant-antioxidantbalance(PAB)anditsassociationwithinflammatorycytokinesinpolycysticovarysyndrome(PCOS)","container-title":"GynecologicalEndocrinology:TheOfficialJournaloftheInternationalSocietyofGynecologicalEndocrinology","page":"148-152","volume":"34","issue":"2","source":"PubMed","abstract":"Chroniclow-gradeinflammationhasbeensuggestedasakeycontributorofthepathogenesisanddevelopmentofpolycysticovarysyndrome(PCOS).Toinvestigatetheassociationbetweenoxidativestressstatusandinflammatorycytokinesinfollicularfluidof21PCOSwomencomparedto21womenwithnormalovarianfunctionwhounderwentintra-cytoplasmicsperminjection.ConcentrationofIL-6,IL-8,IL-10,andTNF-αwasmeasuredusingsandwichELISA.Oxidativestresswasexaminedbymeasu