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  1. NTU Theses and Dissertations Repository
  2. 醫學院
  3. 生理學科所
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/7868
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dc.contributor.advisor胡孟君(Meng-Chun Hu)
dc.contributor.authorYi-Jing Chenen
dc.contributor.author陳怡靜zh_TW
dc.date.accessioned2021-05-19T17:56:37Z-
dc.date.available2026-12-31
dc.date.available2021-05-19T17:56:37Z-
dc.date.copyright2016-08-26
dc.date.issued2016
dc.date.submitted2016-08-18
dc.identifier.citationAtanasov AG, Leiser D, Roesselet C, Noti M, Corazza N, Schoonjans K, Brunner T. 2008. Cell cycle-dependent regulation of extra-adrenal glucocorticoid synthesis in murine intestinal epithelial cells. FASEB J 22: 4117-4125.
Auharek SA, de Franca LR. 2010. Postnatal testis development, Sertoli cell proliferation and number of different spermatogonial types in C57BL/6J mice made transiently hypo- and hyperthyroidic during the neonatal period. J Anat 216: 577-588.
Barthold JS, Gonzalez R. 2003. The epidemiology of congenital cryptorchidism, testicular ascent and orchiopexy. J Urol 170: 2396-2401.
Belvedere P, Dalla Valle L, Vianello S, Carnevali O, Colombo L. 2001. Hormonal steroidogenesis in liver and small intestine of the green frog, Rana esculenta L. Life Sci 69: 2921-2930.
Boivin MA, Ye D, Kennedy JC, Al-Sadi R, Shepela C, Ma TY. 2007. Mechanism of glucocorticoid regulation of the intestinal tight junction barrier. Am J Physiol Gastrointest Liver Physiol 292: G590-598.
Botrugno OA, Fayard E, Annicotte JS, Haby C, Brennan T, Wendling O, Tanaka T, Kodama T, Thomas W, Auwerx J et al. 2004. Synergy between LRH-1 and beta-catenin induces G1 cyclin-mediated cell proliferation. Mol Cell 15: 499-509.
Chang C, Lee SO, Wang RS, Yeh S, Chang TM. 2013. Androgen receptor (AR) physiological roles in male and female reproductive systems: lessons learned from AR-knockout mice lacking AR in selective cells. Biol Reprod 89: 21.
Chung BC, Matteson KJ, Voutilainen R, Mohandas TK, Miller WL. 1986. Human cholesterol side-chain cleavage enzyme, P450scc: cDNA cloning, assignment of the gene to chromosome 15, and expression in the placenta. Proc Natl Acad Sci U S A 83: 8962-8966.
Cima I, Corazza N, Dick B, Fuhrer A, Herren S, Jakob S, Ayuni E, Mueller C, Brunner T. 2004. Intestinal epithelial cells synthesize glucocorticoids and regulate T cell activation. J Exp Med 200: 1635-1646.
Coste A, Dubuquoy L, Barnouin R, Annicotte JS, Magnier B, Notti M, Corazza N, Antal MC, Metzger D, Desreumaux P et al. 2007. LRH-1-mediated glucocorticoid synthesis in enterocytes protects against inflammatory bowel disease. Proc Natl Acad Sci U S A 104: 13098-13103.
Culty M. 2009. Gonocytes, the forgotten cells of the germ cell lineage. Birth Defects Res C Embryo Today 87: 1-26.
Dalla Valle L, Belvedere P, Simontacchi C, Colombo L. 1992. Extraglandular hormonal steroidogenesis in aged rats. J Steroid Biochem Mol Biol 43: 1095-1098.
Dalla Valle L, Couet J, Labrie Y, Simard J, Belvedere P, Simontacchi C, Labrie F, Colombo L. 1995. Occurrence of cytochrome P450c17 mRNA and dehydroepiandrosterone biosynthesis in the rat gastrointestinal tract. Mol Cell Endocrinol 111: 83-92.
De Gendt K, Swinnen JV, Saunders PT, Schoonjans L, Dewerchin M, Devos A, Tan K, Atanassova N, Claessens F, Lecureuil C et al. 2004. A Sertoli cell-selective knockout of the androgen receptor causes spermatogenic arrest in meiosis. Proc Natl Acad Sci U S A 101: 1327-1332.
Fischer A, Gluth M, Weege F, Pape UF, Wiedenmann B, Baumgart DC, Theuring F. 2014. Glucocorticoids regulate barrier function and claudin expression in intestinal epithelial cells via MKP-1. Am J Physiol Gastrointest Liver Physiol 306: G218-228.
Galand G. 1989. Brush border membrane sucrase-isomaltase, maltase-glucoamylase and trehalase in mammals. Comparative development, effects of glucocorticoids, molecular mechanisms, and phylogenetic implications. Comp Biochem Physiol B 94: 1-11.
Gonzalo JA, Gonzalez-Garcia A, Martinez C, Kroemer G. 1993. Glucocorticoid-mediated control of the activation and clonal deletion of peripheral T cells in vivo. J Exp Med 177: 1239-1246.
Grgurevic N, Budefeld T, Rissman EF, Tobet SA, Majdic G. 2008. Aggressive behaviors in adult SF-1 knockout mice that are not exposed to gonadal steroids during development. Behav Neurosci 122: 876-884.
Hsu HJ, Hsu NC, Hu MC, Chung BC. 2006. Steroidogenesis in zebrafish and mouse models. Mol Cell Endocrinol 248: 160-163.
Hu MC, Hsu NC, El Hadj NB, Pai CI, Chu HP, Wang CK, Chung BC. 2002. Steroid deficiency syndromes in mice with targeted disruption of Cyp11a1. Mol Endocrinol 16: 1943-1950.
Huang SC, Lee CT, Chung BC. 2014. Tumor necrosis factor suppresses NR5A2 activity and intestinal glucocorticoid synthesis to sustain chronic colitis. Sci Signal 7: ra20.
Hum DW, Miller WL. 1993. Transcriptional regulation of human genes for steroidogenic enzymes. Clin Chem 39: 333-340.
Hutson JM, Balic A, Nation T, Southwell B. 2010. Cryptorchidism. Semin Pediatr Surg 19: 215-224.
Jegou B. 2015. Paracetamol-induced endocrine disruption in human fetal testes. Nat Rev Endocrinol 11: 453-454.
Kaftanovskaya EM, Huang Z, Barbara AM, De Gendt K, Verhoeven G, Gorlov IP, Agoulnik AI. 2012. Cryptorchidism in mice with an androgen receptor ablation in gubernaculum testis. Mol Endocrinol 26: 598-607.
Kaftanovskaya EM, Neukirchner G, Huff V, Agoulnik AI. 2013. Left-sided cryptorchidism in mice with Wilms' tumour 1 gene deletion in gubernaculum testis. J Pathol 230: 39-47.
Keeney DS, Ikeda Y, Waterman MR, Parker KL. 1995. Cholesterol side-chain cleavage cytochrome P450 gene expression in the primitive gut of the mouse embryo does not require steroidogenic factor 1. Mol Endocrinol 9: 1091-1098.
Kostadinova F, Schwaderer J, Sebeo V, Brunner T. 2014. Why does the gut synthesize glucocorticoids? Ann Med 46: 490-497.
Le Goascogne C, Robel P, Gouezou M, Sananes N, Baulieu EE, Waterman M. 1987. Neurosteroids: cytochrome P-450scc in rat brain. Science 237: 1212-1215.
Livera G, Rouiller-Fabre V, Durand P, Habert R. 2000. Multiple effects of retinoids on the development of Sertoli, germ, and Leydig cells of fetal and neonatal rat testis in culture. Biol Reprod 62: 1303-1314.
Mahato D, Goulding EH, Korach KS, Eddy EM. 2001. Estrogen receptor-alpha is required by the supporting somatic cells for spermatogenesis. Mol Cell Endocrinol 178: 57-63.
Miller WL. 1988. Molecular biology of steroid hormone synthesis. Endocr Rev 9: 295-318.
Mueller M, Cima I, Noti M, Fuhrer A, Jakob S, Dubuquoy L, Schoonjans K, Brunner T. 2006. The nuclear receptor LRH-1 critically regulates extra-adrenal glucocorticoid synthesis in the intestine. J Exp Med 203: 2057-2062.
Noti M, Corazza N, Mueller C, Berger B, Brunner T. 2010. TNF suppresses acute intestinal inflammation by inducing local glucocorticoid synthesis. J Exp Med 207: 1057-1066.
Noti M, Sidler D, Brunner T. 2009. Extra-adrenal glucocorticoid synthesis in the intestinal epithelium: more than a drop in the ocean? Semin Immunopathol 31: 237-248.
Notini AJ, Davey RA, McManus JF, Bate KL, Zajac JD. 2005. Genomic actions of the androgen receptor are required for normal male sexual differentiation in a mouse model. J Mol Endocrinol 35: 547-555.
Oakberg EF. 1956. A description of spermiogenesis in the mouse and its use in analysis of the cycle of the seminiferous epithelium and germ cell renewal. Am J Anat 99: 391-413.
Paniagua R, Nistal M. 1984. Morphological and histometric study of human spermatogonia from birth to the onset of puberty. J Anat 139 ( Pt 3): 535-552.
Parra MT, Viera A, Gomez R, Page J, Benavente R, Santos JL, Rufas JS, Suja JA. 2004. Involvement of the cohesin Rad21 and SCP3 in monopolar attachment of sister kinetochores during mouse meiosis I. J Cell Sci 117: 1221-1234.
Russell LD, Clermont Y. 1977. Degeneration of germ cells in normal, hypophysectomized and hormone treated hypophysectomized rats. Anat Rec 187: 347-366.
Sato T, Matsumoto T, Kawano H, Watanabe T, Uematsu Y, Sekine K, Fukuda T, Aihara K, Krust A, Yamada T et al. 2004. Brain masculinization requires androgen receptor function. Proc Natl Acad Sci U S A 101: 1673-1678.
Scott HM, Hutchison GR, Mahood IK, Hallmark N, Welsh M, De Gendt K, Verhoeven G, O'Shaughnessy P, Sharpe RM. 2007. Role of androgens in fetal testis development and dysgenesis. Endocrinology 148: 2027-2036.
Singh SR, Burnicka-Turek O, Chauhan C, Hou SX. 2011. Spermatogonial stem cells, infertility and testicular cancer. J Cell Mol Med 15: 468-483.
Smith LB, Walker WH. 2014. The regulation of spermatogenesis by androgens. Semin Cell Dev Biol 30: 2-13.
Solomon NS, Gartner H, Oesterreicher TJ, Henning SJ. 2001. Development of glucocorticoid-responsiveness in mouse intestine. Pediatr Res 49: 782-788.
Traut W, Endl E, Scholzen T, Gerdes J, Winking H. 2002. The temporal and spatial distribution of the proliferation associated Ki-67 protein during female and male meiosis. Chromosoma 111: 156-164.
Tremblay JJ. 2010. What signals testis descent? Biol Reprod 83: 687-689.
Walker WH. 2011. Testosterone signaling and the regulation of spermatogenesis. Spermatogenesis 1: 116-120.
Wang M, Ramirez J, Han J, Jia Y, Domenico J, Seibold MA, Hagman JR, Gelfand EW. 2013. The steroidogenic enzyme Cyp11a1 is essential for development of peanut-induced intestinal anaphylaxis. J Allergy Clin Immunol 132: 1174-1183 e1178.
Wang RS, Yeh S, Chen LM, Lin HY, Zhang C, Ni J, Wu CC, di Sant'Agnese PA, deMesy-Bentley KL, Tzeng CR et al. 2006. Androgen receptor in sertoli cell is essential for germ cell nursery and junctional complex formation in mouse testes. Endocrinology 147: 5624-5633.
Wang Y, Ge W. 2004. Cloning of zebrafish ovarian P450c17 (CYP17, 17alpha-hydroxylase/17, 20-lyase) and characterization of its expression in gonadal and extra-gonadal tissues. Gen Comp Endocrinol 135: 241-249.
Wen Q, Zheng QS, Li XX, Hu ZY, Gao F, Cheng CY, Liu YX. 2014. Wt1 dictates the fate of fetal and adult Leydig cells during development in the mouse testis. Am J Physiol Endocrinol Metab 307: E1131-1143.
Wrobel KH, Bickel D, Kujat R. 1996. Immunohistochemical study of seminiferous epithelium in adult bovine testis using monoclonal antibodies against Ki-67 protein and proliferating cell nuclear antigen (PCNA). Cell Tissue Res 283: 191-201.
Wu X, Schmidt JA, Avarbock MR, Tobias JW, Carlson CA, Kolon TF, Ginsberg JP, Brinster RL. 2009. Prepubertal human spermatogonia and mouse gonocytes share conserved gene expression of germline stem cell regulatory molecules. Proc Natl Acad Sci U S A 106: 21672-21677.
Yeh S, Tsai MY, Xu Q, Mu XM, Lardy H, Huang KE, Lin H, Yeh SD, Altuwaijri S, Zhou X et al. 2002. Generation and characterization of androgen receptor knockout (ARKO) mice: an in vivo model for the study of androgen functions in selective tissues. Proc Natl Acad Sci U S A 99: 13498-13503.
Zhang FP, Poutanen M, Wilbertz J, Huhtaniemi I. 2001. Normal prenatal but arrested postnatal sexual development of luteinizing hormone receptor knockout (LuRKO) mice. Mol Endocrinol 15: 172-183.
羅文均. 2009. Characterization of Cyp11a1 expression in mice retina and retinal development in Cyp11a1 knockout mice. in Graduate Institute of Physiology College of Medicine National Taiwan University Master Thesis.
dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/7868-
dc.description.abstractCyp11a1基因在類固醇荷爾蒙生成過程中扮演著關鍵角色,在性腺控制性荷爾蒙生成,調控生殖作用。本論文利用Cyp11a1基因剔除小鼠(Cyp11a1-/-)探討類固醇對小鼠睪丸發育的影響。我們發現相較於野生型小鼠,8週大Cyp11a1-/-的睪丸重量小且無法正常沉降;此外,左側睪丸位置較右側高,重量也較小。Cyp11a1-/-睪丸細精管管徑小且觀察不到成熟精子,Leydig cell數量增加有肥大現象。免疫螢光染色分析結果顯示,Cyp11a1-/-細精管中沒有長型精細胞(elongated spermatid),僅在極少數細精管觀察到少量的圓形精細胞(round spermatid),另有大量生殖母細胞(spermatocyte)累積的現象,主要停留在粗絲期(pachytene)階段,少數則停在偶線(zygotene)階段。似乎有 較多未分化的精原幹細胞(undifferentiated spermatogonia stem cell)數量在Cyp11a1-/-細精管中,出生3天的Cyp11a1-/-生殖母細胞(gonocyte)的數量也多於Cyp11a1+/+。TUNEL實驗顯示,8週Cyp11a1-/-生殖細胞的凋亡明顯地增加許多。這些結果說明,Cyp11a1基因對精子生成過程的減數分裂時期是很重要的。
有些週邊組織亦有自行生成類固醇荷爾蒙的能力,已知Cyp11a1基因會表現在小腸,因此我們也觀察Cyp11a1-/-剔除對小腸的影響。在8週Cyp11a1-/-小腸絨毛,我們看到一些異常現象,包括,腸上皮細胞增厚為多層,上皮細胞與lamina propria脫離,微血管充血以及疑似免疫細胞浸潤。經BrdU注射在3天和8週小鼠小腸觀察到Cyp11a1-/-crypt細胞增生明顯少於Cyp11a1+/+。這些結果說明Cyp11a1基因在小鼠小腸發育可能扮演著重要的調控角色。
zh_TW
dc.description.provenanceMade available in DSpace on 2021-05-19T17:56:37Z (GMT). No. of bitstreams: 1
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Previous issue date: 2016
en
dc.description.tableofcontents目錄 II
表次 IV
圖次 V
中文摘要 VI
英文摘要 VII
第一章 導論 1
一、 類固醇荷爾蒙之生成 1
二、 睪丸 1
1. 睪丸結構 1
2. 精子生成(spermatogenesis) 2
3. 雄性素(Androgen)對精子生成的重要性 3
三、 小腸 3
1. 醣皮質類固醇(glucocorticoid)對小腸的影響 4
四、 研究動機與目的 5
第二章 材料與方法 7
一、 基因轉殖小鼠 7
1. Cyp11a1+/-異合子 7
2. Cyp11a1-/- 基因剔除小鼠 7
3. Cyp11a1-/- 腎上腺移植 7
二、 小鼠基因型鑑定(Genotyping) 8
三、 BrdU(5-Bromo-2-deoxyuridine)處理 9
四、 灌流 9
五、 冷凍切片 10
1. 睪丸 10
2. 小腸組織 10
六、 石蠟組織切片(Paraffin Section) 10
七、 蘇木素-伊紅(hematoxylin-eosin,HE)染色 11
八、 Periodic acid-Schiff(PAS)染色 11
九、 免疫組織螢光染色 11
十、 BrdU螢光染色 13
十一、 細胞凋亡(apoptosis)分析 13
十二、 統計分析 13
第三章 結果 14
一、 Cyp11a1-/-小鼠產生 14
二、 Cyp11a1基因剔除對睪丸發育的影響 14
三、 Cyp11a1基因剔除對精子生成(spermatogenesis)的影響 15
1. 精細胞(spermatid) 15
2. 精母細胞(spermatocyte) 16
3. 未分化的精原幹細胞(Undifferentiated spermatogonia stem cell) 17
4. 生殖母細胞(Gonocyte) 17
5. 賽氏細胞(Sertoli cell) 17
四、 Cyp11a1基因剔除影響睪丸細胞增生與凋亡 18
五、 Cyp11a1基因剔除對小鼠小腸型態的影響 18
六、 Cyp11a1基因剔除對小腸細胞增生與凋亡的影響 19
第四章 討論 20
一、 Cyp11a1基因剔除小鼠睪丸左右兩側不正常沉降 20
二、 比較雄性Cyp11a1基因剔除與Androgen receptor剔除小鼠 21
三、 Cyp11a1基因剔除小鼠睪丸中Leydig cell型態肥大 22
四、 Cyp11a1在小腸中所扮演的角色 22
參考文獻 24
dc.language.isozh-TW
dc.titleCyp11a1基因剔除對小鼠睪丸與小腸發育之影響zh_TW
dc.titleEffects of Cyp11a1 knockout on the development of mouse testis and intestineen
dc.typeThesis
dc.date.schoolyear104-2
dc.description.degree碩士
dc.contributor.oralexamcommittee鍾邦柱(Bon-chu Chung),林盈宏(Ying-Hung Lin),李立仁(Li-Jen Lee)
dc.subject.keywordCyp11a1,睪丸,生殖細胞,小腸,zh_TW
dc.subject.keywordCyp11a1,testis,germ cells,intestine,en
dc.relation.page55
dc.identifier.doi10.6342/NTU201603243
dc.rights.note同意授權(全球公開)
dc.date.accepted2016-08-18
dc.contributor.author-college醫學院zh_TW
dc.contributor.author-dept生理學研究所zh_TW
dc.date.embargo-lift2026-12-31-
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