本文選題：BPA　切入點(diǎn)：睪丸　出處：《南京醫(yī)科大學(xué)》2012年碩士論文

【摘要】：雙酚A（bisphenol A，BPA）是酚類環(huán)境雌激素的一種，結(jié)構(gòu)類似于雌二醇（E2）和己烯雌酚（diethylstilbestrol，DES），主要用于生產(chǎn)聚碳酸酯、環(huán)氧樹脂、聚砜樹脂、聚苯醚樹脂等多種高分子材料，也可用于生產(chǎn)增塑劑、阻燃劑、抗氧化劑、熱穩(wěn)定劑、橡膠防老化劑、農(nóng)藥、涂料等精細(xì)化工產(chǎn)品，這些物品的反復(fù)使用及暴露于高熱環(huán)境會(huì)導(dǎo)致BPA的浸出。BPA不僅在多種環(huán)境介質(zhì)和低等生物體中被廣泛檢出，而且在許多國(guó)家人群樣本，如血液、尿液、精液、羊水、乳汁中等，也不斷有被檢出的報(bào)道[1]，這表明BPA能通過(guò)胎盤屏障，影響子代的發(fā)育。 本研究的目的是探討圍產(chǎn)期低劑量BPA暴露對(duì)雄性子代生殖系統(tǒng)的影響及其機(jī)制。SD大鼠妊娠期第10d至產(chǎn)后第7d（GD10－PND7）皮下注射BPA2ug/kgbw/d，檢測(cè)F1代雄性大鼠：①PND18、PND21、PND24血清卵泡刺激素（FSH）、黃體生成素（LH）、血清睪酮（T）、血清雌激素（E2）及睪丸內(nèi)睪酮水平；②PND11、PND18、PND21、PND24體重和睪丸重；③睪丸組織形態(tài)學(xué)改變；④PND54（SD雄性大鼠附睪尾部第一波精子出現(xiàn)的時(shí)間點(diǎn)）附睪尾部精子數(shù)目以及形態(tài)學(xué)改變。 研究結(jié)果顯示：①?gòu)腜ND21開始，BPA組F1代雄性血清卵泡刺激素（FSH）、黃體生成素（LH）水平明顯高于control組，而睪丸內(nèi)睪酮水平相對(duì)于control組下降；②從PND21開始，BPA組F1代雄性體重相對(duì)于control組增加；③PND24（SD雄性大鼠睪丸生精小管精子細(xì)胞出現(xiàn)的時(shí)間點(diǎn)），，BPA組F1代雄性精子細(xì)胞陽(yáng)性的生精小管數(shù)占總生精小管數(shù)的百分比、平均每個(gè)生精小管的精子細(xì)胞數(shù)目、生精小管直徑明顯高于control組；④PND54，BPA組F1代雄性附睪尾部第一波精子畸形率明顯高于control組。因此我們推測(cè)圍產(chǎn)期BPA的暴露可能影響了F1代雄性睪丸生精細(xì)胞減數(shù)分裂細(xì)胞周期，減數(shù)分裂異常，第一波精子畸形率增加。 為了探尋BPA組F1代雄性睪丸內(nèi)睪酮水平下降的機(jī)制，我們運(yùn)用real-timePCR，檢測(cè)了F1代雄性睪丸內(nèi)睪酮合成相關(guān)限速酶基因star、p450scc、CYP17a、3-HSD、173-HSD的相對(duì)mRNA水平，和control組相比，BPA組大部分都存在下降趨勢(shì)，且BPA組3-HSD相對(duì)mRNA水平在PND21明顯低于control組。 為了探尋BPA組F1代雄性大鼠睪丸生精細(xì)胞減數(shù)分裂細(xì)胞周期異常的機(jī)制，我們運(yùn)用real-timePCR檢測(cè)了F1代雄性睪丸內(nèi)減數(shù)分裂細(xì)胞周期蛋白及其激酶基因和checkpoint基因相對(duì)mRNA水平。周期蛋白基因cyclinA1相對(duì)mRNA水平在PND21、PND24的BPA組明顯高于control組；checkpoint基因TRIP13相對(duì)mRNA水平在PND21的BPA組明顯低于control組；這些基因?qū)τ跍p數(shù)分裂的過(guò)程是至關(guān)重要的，因此我們推測(cè)這些基因相對(duì)mRNA水平的差異可能和睪丸形態(tài)學(xué)以及精子形態(tài)學(xué)差異有聯(lián)系。我們結(jié)合形態(tài)學(xué)表型以及這些基因的表達(dá)趨勢(shì)，尋找到F1代雄性睪丸內(nèi)與精子發(fā)生相關(guān)的c-jun、c-fos原癌基因相對(duì)mRNA水平在BPA組和control組差異有明顯差異。 因此我們推測(cè)圍產(chǎn)期SD大鼠低劑量BPA暴露，可能影響了F1代雄性大鼠睪丸生精細(xì)胞減數(shù)分裂的相關(guān)事件，從而促使精子發(fā)生紊亂，第一波精子畸形率增加，為進(jìn)一步探討EDCs導(dǎo)致男性不育的分子機(jī)制提供基礎(chǔ)。
[Abstract]:Bisphenol A (bisphenol A BPA) is a kind of phenolic environmental estrogens, a structure similar to estradiol (E2) and diethylstilbestrol (diethylstilbestrol, DES), mainly for the production of polycarbonate, epoxy resin, polysulfone resin, a polyphenylene ether resin and other polymer materials, can also be used in the production of plasticizer, flame retardant antioxidant, heat stabilizer, anti ageing agent, rubber, pesticide, paint and other fine chemical products, these items for repeated use and exposure to high temperature environment will lead to the leaching of.BPA BPA not only in various environmental media and lower organisms are widely detected in many countries, and the population samples, such as blood, urine, semen, amniotic fluid. Milk medium, also have been reported to be detected [1], suggesting that BPA can pass through the placenta barrier and affect the development of the offspring.
The purpose of this study is to explore the perinatal exposure to low doses of BPA the reproductive system of male offspring and its mechanism in.SD rats during pregnancy and postpartum in 10d 7d (GD10 PND7) by subcutaneous injection of BPA2ug/kgbw/d, detection of F1 generation male rats: PND18, PND21, PND24 of serum follicle stimulating hormone, luteinizing hormone (FSH) erythropoietin (LH), serum testosterone (T), serum estradiol (E2) and intratesticular testosterone levels; the PND11, PND18, PND21, PND24 body weight and testis weight; the change of testicular tissue morphology; 4 PND54 (SD male rat epididymal sperm at the first time point) change of epididymal sperm the number and morphology.
The results showed as follows: starting from PND21, BPA group of F1 generation male serum follicle stimulating hormone (FSH), luteinizing hormone (LH) levels were significantly higher than that of control group, and the testosterone level in comparison to the control group decreased; the PND21 from the beginning, BPA group of F1 generation male weight compared with group control and PND24 (SD increase; male rat seminiferous tubule sperm cells the time), the percentage of the total number of seminiferous tubules seminiferous tubules in group BPA of F1 generation male sperm cells were positive, the average number of sperm cells in the seminiferous tubules of the seminiferous tubule diameter was significantly higher than that of control group; the PND54, BPA group of F1 generation male the first wave of epididymal sperm malformation rate was significantly higher than control group. So we speculate that BPA may affect the perinatal exposure of F1 generation male spermatogenic cell meiotic cell cycle, abnormal meiosis, the first wave of sperm deformity rate increased.
In order to explore the mechanism of testosterone in the testis of male BPA group decreased F1, we use real-timePCR, the detection of F1 generation male testicular testosterone synthesis related enzyme gene star, P450scc, CYP17a, 3-HSD, relative mRNA level of 173-HSD, compared with control group, BPA group of have downward trend, and the relative mRNA the level of BPA 3-HSD in group PND21 was significantly lower than that of control group.
In order to explore the mechanism of the BPA group of F1 generation male rats testis spermatogenic cell meiotic cell cycle abnormalities, we used real-timePCR to detect F1 generation male testis meiotic cell cycle protein and its relative level of mRNA kinase gene and checkpoint gene. The relative level of mRNA cyclin gene cyclinA1 in PND21, BPA group PND24 was significantly higher than control group mRNA; relative level of checkpoint gene in TRIP13 was significantly lower than that in control group BPA group PND21; these genes are essential for meiosis, so we speculate that these genes relative to the differences in the level of mRNA and the morphology of the testis and sperm morphological differences are linked. We combine the morphological phenotype and gene expression trend of these, to find the associated the c-Jun and F1 generation male sperm in the testis c-fos gene relative to the mRNA level in BPA group and control group There is a significant difference in the difference.
We therefore hypothesized that perinatal SD rats of low dose BPA exposure may affect the related events of F1 generation male rat spermatogenic cells meiosis, thus contributing tospermatogenesis disorder, the first wave of sperm deformity rate increased, provide the basis for the molecular mechanism of male sterility for the further study of EDCs causes.

【學(xué)位授予單位】：南京醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R114

【共引文獻(xiàn)】

相關(guān)期刊論文 前4條

1 王承敏;楊克敵;;雙酚A雄性生殖系統(tǒng)毒性的研究進(jìn)展[J];環(huán)境衛(wèi)生學(xué)雜志;2012年04期

2 覃丹丹;袁偉;高爾生;;雙酚A對(duì)雄性生殖功能影響的研究進(jìn)展[J];環(huán)境與健康雜志;2007年07期

3 吳建輝;孫祖越;;雙酚A雄性生殖毒性研究進(jìn)展[J];環(huán)境與健康雜志;2009年05期

4 楊丹;李丹丹;劉姍姍;嚴(yán)云勤;;雙酚A對(duì)機(jī)體的影響及其作用機(jī)制[J];現(xiàn)代預(yù)防醫(yī)學(xué);2008年17期

相關(guān)會(huì)議論文 前1條

1 賀天鋒;陳奕;;雙酚A的生殖毒性研究進(jìn)展[A];華東地區(qū)第十次流行病學(xué)學(xué)術(shù)會(huì)議暨華東地區(qū)流行病學(xué)學(xué)術(shù)會(huì)議20周年慶典論文匯編[C];2010年

相關(guān)博士學(xué)位論文 前1條

1 周芩;雙酚A對(duì)男性生殖功能的影響及機(jī)制探討[D];山西醫(yī)科大學(xué);2013年

相關(guān)碩士學(xué)位論文 前10條

1 趙文慧;基于亞微米硅膠的偽模板分子印跡聚合物選擇性萃取水樣中痕量雙酚A[D];南京醫(yī)科大學(xué);2010年

2 王群;雙酚A誘導(dǎo)小鼠睪丸生殖細(xì)胞凋亡的分子機(jī)制[D];安徽醫(yī)科大學(xué);2011年

3 王軒;雙酚A對(duì)雄性大鼠的生殖內(nèi)分泌毒效應(yīng)及其機(jī)制研究[D];南京醫(yī)科大學(xué);2011年

4 葉長(zhǎng)英;微球型TiO_2的超聲制備、表征及光催化降解內(nèi)分泌干擾素雙酚A的研究[D];重慶理工大學(xué);2011年

5 俞錚錚;微營(yíng)養(yǎng)素對(duì)不育模型大鼠生殖功能影響的研究[D];浙江大學(xué);2008年

6 楊丹;雙酚A對(duì)小鼠子宮的影響及其作用機(jī)制的研究[D];東北農(nóng)業(yè)大學(xué);2008年

7 賀天鋒;雙酚A、雌激素受體基因多態(tài)性對(duì)女性職業(yè)暴露人群生殖功能影響研究[D];蘇州大學(xué);2009年

8 聞霞;青春期接觸雙酚A對(duì)雄性大鼠生殖系統(tǒng)影響及機(jī)制研究[D];吉林大學(xué);2010年

9 程治良;內(nèi)分泌干擾物——雙酚A的高效光催化降解研究[D];重慶理工大學(xué);2010年

10 梁娜娜;探究MWCNT-COOH/BPA復(fù)合物的母鼠暴露對(duì)其子代的影響[D];山東大學(xué);2012年

本文編號(hào)：1666127