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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 胡孟君 | |
dc.contributor.author | Shuo-Hui Hsu | en |
dc.contributor.author | 徐碩惠 | zh_TW |
dc.date.accessioned | 2021-06-16T02:37:14Z | - |
dc.date.available | 2025-07-24 | |
dc.date.copyright | 2015-09-25 | |
dc.date.issued | 2015 | |
dc.date.submitted | 2015-07-24 | |
dc.identifier.citation | Baker, T. G., 1971 Radiosensitivity of mammalian oocytes with particular reference to the human female. Am J Obstet Gynecol 110: 746-761.
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/54031 | - |
dc.description.abstract | 膽固醇側鏈裂解酶(cytochrome P450 side chain cleavage,P450scc)為Cyp11a1基因的產物,擔任類固醇賀爾蒙生成的速率決定步驟,能將膽固醇轉化為孕烯醇酮(pregnenolone)。然而,在小鼠動物模式當中,Cyp11a1基因經全面性剔除 (Cyp11a1-/-)之後會導致嚴重的腎上腺功能不足,小鼠出生不久即死亡,因此未能探究Cyp11a1基因在成鼠性腺中所扮演的角色。為了突破這個限制,我們使用Cre/loxP重組酶系統將性腺中的Cyp11a1基因選擇性剔除,此性腺Cyp11a1基因條件式剔除小鼠(Cyp11a1f/f;SCCmtp-Cre、Cyp11a1f/-;SCCmtp-Cre)能夠存活至成鼠並且擁有正常的外生殖器特徵。經西方墨點分析,Cyp11a1f/-;SCCmtp-Cre小鼠睪丸的P450scc蛋白質量與野生型Cyp11a1f/f 相比,下降了83.4%。雖然P450scc蛋白質量有大幅度的下降,但並不影響Cyp11a1f/-;SCCmtp-Cre小鼠精子形成及生殖功能。Cyp11a1f/f;SCCmtp-Cre與Cyp11a1f/-;SCCmtp-Cre小鼠卵巢組織的P450scc蛋白質量與Cyp11a1f/f 相比則是分別下降了96.5%和98.2%。Cyp11a1f/f;SCCmtp-Cre與Cyp11a1f/-;SCCmtp-Cre的卵巢組織切片,可以觀察到發育中各個時期的濾泡與黃體,但黃體以及卵巢基質細胞的細胞質中充滿空泡。經腎上腺移植存活的Cyp11a1-/- 成鼠,也有正常濾泡,但無黃體產生。Cyp11a1f/f;SCCmtp-Cre與Cyp11a1f/-;SCCmtp-Cre具有正常型態的子宮,但Cyp11a1-/- 雌鼠子宮發育不全。Cyp11a1f/-;SCCmtp-Cre 雌鼠擁有正常的性週期,於超排卵試驗能夠排出正常數量的卵,且受精卵在體外培養有能力發育至二細胞期。然而,Cyp11a1f/-;SCCmtp-Cre雌鼠無法懷孕,Cyp11a1f/f;SCCmtp-Cre雌鼠則具有生殖能力。根據上述結果可以歸納出,卵巢中P450scc蛋白質量多寡為子宮發育、排卵能力與生殖能力的關鍵性因素。 | zh_TW |
dc.description.abstract | Cyp11a1 encodes cytochrome P450scc, the mitochondrial cholesterol side chain cleavage enzyme, is the only enzyme that catalyzes the conversion of cholesterol to pregnenolone and, thus, is required for the biosynthesis of all steroid hormones. Cyp11a1 knockout mice (Cyp11a1-/- ) died shortly after birth because of severe adrenal insufficiency; however, the roles of Cyp11a1 in the gonads remain unclear. In this study, we used a Cre/loxP approach to specifically knockout Cyp11a1 in gonads. Both male and female conditional knockout mice (Cyp11a1f/f;SCCmtp-Cre, Cyp11a1f/-;SCCmtp-Cre) survive to adulthood with normal gross external phenotype. Western blot analysis revealed that the protein levels of P450scc in testis are reduced by 83.4% in Cyp11a1f/-;SCCmtp-Cre mice compared to wild-type Cyp11a1f/f. Adult male Cyp11a1f/-;SCCmtp-Cre mice are fertile and have normal sperm formation in testis. In ovary, the protein levels of P450scc were reduced by 96.5% and 98.2% in Cyp11a1f/f;SCCmtp-Cre and Cyp11a1f/-;SCCmtp-Cre, respectively. Ovary of Cyp11a1f/f;SCCmtp-Cre and Cyp11a1f/-;SCCmtp-Cre mice displayed various stages of follicles and corpus luteum; however, the cytoplasmic vacuolation is found in luteal cells. The vacuolated cytoplasm was also present in the stromal cells in Cyp11a1f/f;SCCmtp-Cre and Cyp11a1f/-;SCCmtp-Cre ovary. Cyp11a1-/- mice can be rescued and survived to adulthood by adrenal transplantation. Cyp11a1-/- female appeared have normal follicles, but the corpus luteum was not found in the ovary. Cyp11a1f/f;SCCmtp-Cre and Cyp11a1f/-;SCCmtp-Cre female had normal uterus, however, the uterus of Cyp11a1-/- mice exhibited significant underdevelopment. The female Cyp11a1f/-;SCCmtp-Cre mice have normal estrus cycle and showed responses to superovulation treatment to produced fertilized eggs that can develop into 2-cell stage in vitro. However, Cyp11a1f/-;SCCmtp-Cre female mice are infertile. In contrast, Cyp11a1f/f;SCCmtp-Cre female mice are fertile. Our findings suggest that the protein levels of P450scc in ovary play a key role in uterus development, ovulation and reproductive capacity. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T02:37:14Z (GMT). No. of bitstreams: 1 ntu-104-R02441013-1.pdf: 2882149 bytes, checksum: deaaed0f76b9017f19d114e7402e5307 (MD5) Previous issue date: 2015 | en |
dc.description.tableofcontents | 目錄 II
表次 V 圖次 V 中文摘要 VI 英文摘要 VII 第一章 導論 1 一. 類固醇賀爾蒙之生成(steroidogenesis) 1 二. 性腺(gonads) 1 1. 睪丸 2 2. 卵巢 2 (1) 卵子生成 2 (2) 卵子的成熟 3 (3) 排卵 3 (4) 分泌性賀爾蒙 4 三. Cyp11a1基因在性腺中的表現 4 1. Cyp11a1基因於性腺的分布 4 2. 人類CYP11A1啟動子於性腺中的調控 5 四. SCCmtp-Cre基因轉殖小鼠之建立 6 1. Cre-loxp系統於條件式基因剔除(conditional knockout)上的應用 6 2. 驗證轉殖動物體內Cre重組酶之活性 7 3. SCCmtp-Cre基因轉殖小鼠 7 五. 研究動機與目的 8 第二章 材料與方法 9 一、 基因轉殖鼠之產生 9 1. SCCmtp-Cre基因轉殖鼠 9 2. Cyp11a1f/f 基因轉殖鼠 9 3. Cyp11a1+/-異合子小鼠 9 4. Cyp11a1f/-;SCCmtp-Cre基因條件式剔除鼠 9 5. Cyp11a1-/- 基因剔除小鼠 10 二、 小鼠基因型檢測 10 三、 冷凍組織切片 11 四、 蘇木素-伊紅(hematoxylin-eosin)染色 12 五、 免疫組織化學染色 12 六、 免疫組織螢光染色 13 七、 西方墨點法 13 1. 組織蛋白質萃取 13 2. 聚丙烯胺膠體電泳 14 3. 轉印及免疫染色 14 八、 小鼠生育能力試驗 15 九、 性週期陰道抹片觀察 16 十、 小鼠超排卵及胚胎體外培養 16 十一、 乳腺之全組織包埋染色 17 十二、 統計分析 17 第三章 結果 18 一. 性腺Cyp11a1f/-;SCCmtp-Cre基因條件式剔除小鼠之產生 18 二. Cyp11a1-/- 基因剔除小鼠之產生 18 三. Cyp11a1f/-;SCCmtp-Cre基因條件式剔除小鼠性腺中Cyp11a1基因剔除之效率 19 四. 雄性小鼠性腺發育型態之比較 20 五. 雌性小鼠性腺發育型態之比較 21 六. Cyp11a1f/-;SCCmtp-Cre 雌鼠擁有正常性週期 22 七. Cyp11a1f/-;SCCmtp-Cre雌鼠不具有生殖能力 23 八. Cyp11a1f/-;SCCmtp-Cre 雌鼠之排卵能力正常 23 九. Cyp11a1條件式基因剔除對卵巢中基因表現之影響 23 1. Cyp11a1 24 2. Hsd3b 24 3. Pgr 24 4. Calb2 25 十. Cyp11a1基因選擇性剔除造成小鼠乳腺發育延遲 25 第四章 討論 27 一. Cyp11a1f/-;SCCmtp-Cre因條件式剔除小鼠之建立 27 二. Cyp11a1f/-;SCCmtp-Cre小鼠性腺中Cyp11a1基因剔除之效率 27 三. 雄性Cyp11a1 基因剔除小鼠之性腺發育型態 28 四. Cyp11a1-/-、Cyp11a1f/f;SCCmtp-Cre與Cyp11a1f/-;SCCmtp-Cre雌性小鼠之比較 29 1. 子宮發育 30 2. 卵巢組織 30 3. 生殖能力 30 4. 乳腺發育 31 五. 雌性Cyp11a1基因剔除與其他基因剔除模式之比較 31 1. 內生殖器官 31 2. 卵巢組織 32 3. 生殖能力 32 參考文獻 34 表次 表一、生殖能力試驗 38 表二、Cyp11a1基因剔除小鼠之比較 39 表三、Cyp11a1與其他基因剔除雌鼠之比較 40 圖次 圖一、Cyp11a1f/-;SCCmtp-Cre基因轉殖小鼠之基因型鑑定 41 圖二、Cyp11a1-/- 基因剔除小鼠之基因型鑑定 42 圖三、腎上腺中P450scc的表現 43 圖四、性腺中P450scc的表現 44 圖五、雄性小鼠生殖系統外觀之比較 45 圖六、小鼠睪丸組織型態之比較 46 圖七、雌性小鼠生殖系統外觀之比較 47 圖八、小鼠卵巢組織型態之比較 48 圖九、Cyp11a1+/+、Cyp11a1-/- 小鼠卵巢組織型態之比較 49 圖十、成熟濾泡之直徑 50 圖十一、Cyp11a1基因條件式剔除小鼠之性週期檢測 51 圖十二、超排卵試驗 52 圖十三、Cyp11a1-/- 基因剔除小鼠睪丸中Cyp11a1基因表現 53 圖十四、小鼠卵巢中Cyp11a1基因表現 54 圖十五、PR、3βHSD、Calretinin在卵巢之表現 55 圖十六、Cyp11a1基因條件式剔除對小鼠乳管發育之影響 56 圖十七、Cyp11a1基因剔除對小鼠乳腺發育之影響 57 附圖一、SCCmtp-Cre轉殖基因於腎上腺與性腺的分布情形 58 | |
dc.language.iso | zh-TW | |
dc.title | 探討Cyp11a1基因缺乏對小鼠生殖之影響 | zh_TW |
dc.title | Effect of Cyp11a1 deficiency on mouse reproduction | en |
dc.type | Thesis | |
dc.date.schoolyear | 103-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 鍾邦柱,陳佑宗,高淑慧 | |
dc.subject.keyword | Cyp11a1基因缺乏,生殖, | zh_TW |
dc.subject.keyword | Cyp11a1 deficiency,reproduction, | en |
dc.relation.page | 58 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2015-07-24 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 生理學研究所 | zh_TW |
顯示於系所單位: | 生理學科所 |
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