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Research On Fine Particulate Matter Exposure Caused Male Reproductive Function Impairment And Its Mechanism

Posted on:2018-11-04Degree:DoctorType:Dissertation
Country:ChinaCandidate:X N CaoFull Text:PDF
GTID:1314330536971714Subject:Academy of Pediatrics
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BackgroundSterility is a global challenge that threatens human ' s reproductive health,and male factor is about account for 50%,sperm quality is the key reason for male infertility.Epidemiologic studies demonstrated that fine particulate matter PM2.5 can impaired male sperm quality directly,but the specific mechanism remains unclear.ObjectiveThis research aims to explore the underlying of male reproductive impairment caused by PM2.5,so as to establish scientific experimental basement for formulating environmental protection policy and preventing and curing male reproductive problems.MethodsPM2.5-exposed SD rat models were established.In the first and the third part research,four week old rats were randomly divided into saline control group,PM2.5 low dose exposure group(9 mg/kg.b.w.)and PM2.5 high dose exposure group(24 mg/kg.b.w.)for eight weeks,once a day,respectively.In the second part research,six week old rats were randomly divided into saline control group,PM2.5 low dose exposure group(10 mg/kg.b.w.)and PM2.5 high dose exposure group(20 mg/kg.b.w.)for four weeks,once a day,respectively.After exposure,performed mating test,analyzed sperm quality,observed histological change of epididymis and testis,examined expressions of spermatogenesis markers including DMC1,Plzf,SCP3,Stra8 and blood-testis barrier(BTB)junction protein including occluding,ZO-1,?-catenin,Cx43 and PI3K/Akt signaling pathway activity.Meanwhile,primary Sertoli cells were exposed to PM2.5,examined ROS levels and apoptosis and oxidative stress levels of testis.ResultsCompared with control group,after PM2.5 exposure,the rate of mating test was distinctly declined,sperm count significantly reduced and abnormality rate significantly raised,the number of sperms in epididymis tubes were conspicuously lowered,morphology of seminiferous tubules was obviously abnormal and germ cells were apparently lessened,spermatogenesis markers expressions were obviously decreased in high dose exposure group,and PI3K/Akt signaling pathway activity in testis was significantly up-regulated,expressions of BTB junction protein including occludin,ZO-1,?-catenin and Cx43 were significantly decreased.Compared with control group,ROS levels of Sertoli cells apoptosis rate significantly increased in PM2.5 exposure groups.ConclusionFine particulate matter up-regulated PI3K/Akt signaling pathway,caused oxidative stress injury in testis and Sertoli cells,then apoptosis of Sertoli cells increased,BTB junction protein expressions were decreased,BTB integrity was disrupted,and spermatogenesis microenvironment was damaged,sperm quality was reduced,and thus led to male infertility.
Keywords/Search Tags:Fine particulate matter, Testis, Blood-testis barrier(BTB), Oxidative stress
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