遺伝子導入を用いた精子形成の試みと男子不妊臨床応用に向けた基礎的研究

• 研究課題/領域番号: 18689039
• 研究種目: 若手研究(A)
• 配分区分: 補助金
• 研究分野: 泌尿器科学
• 研究機関: 名古屋市立大学
• 研究代表者: 小島 祥敬 名古屋市立大学, 大学院・医学研究科, 講師 (60305539)
• 研究期間 (年度): 2006 – 2008
• 研究課題ステータス: 完了 (2008年度)
• 配分額: 13,780千円 (直接経費: 10,600千円、間接経費: 3,180千円); 2008年度: 3,380千円 (直接経費: 2,600千円、間接経費: 780千円); 2007年度: 4,550千円 (直接経費: 3,500千円、間接経費: 1,050千円); 2006年度: 5,850千円 (直接経費: 4,500千円、間接経費: 1,350千円)
• キーワード: 男子不妊症 / 精巣 / 遺伝子導入 / 転写因子 / 造精機能 / アデノウイルスベクター / DAX-1

研究概要

アデノウイルスベクターは男子不妊症治療を前提とした精巣内遺伝子導入法としては最も優れた遺伝子導入法であることを明らかにした。DAX-1およびAd4BP/SF-1をアデノウイルスベクターに組み込み、精巣体細胞への遺伝子導入を試みた。

研究成果

• [雑誌論文] Laparoscopic diagnosis and treatment of a phenotypic girl with a mosaic 45,XO/46,X,idic(Y) mixed gonadal dysgenesis. (2009)
  • 著者名/発表者名: Mizuno K, Kojima Y, Kurokawa S, Mizuno H, Kohri K, Hayashi Y.
  • 雑誌名: J Pediar Surg 44
  • 査読あり
• [雑誌論文] Activation of NF-kappaB associated with germ cell apoptosis in testes of experimentally induced cryptorchid rat model. (2009)
  • 著者名/発表者名: Mizuno K, Hayashi Y, Kojima Y, Nakane A, Tozawa K, Kohri K.
  • 雑誌名: Urology 73 ページ: 389-93
  • 査読あり
• [雑誌論文] Pax2 overexpression in embryoid bodies induces upregulation of integrin alpha8 and aquaporin-1. (2009)
  • 著者名/発表者名: Nakane A, Kojima Y, Hayashi Y, Kohri K, Masui S, Nishinakamura R.
  • 雑誌名: In Vitro Cell Dev Biol Anim 45 ページ: 62-68
  • 査読あり
• [雑誌論文] Identification of differentially expressed genes in human cryptorchid testes using suppression subtractive hybridization. (2009)
  • 著者名/発表者名: Mizuno K, Kojima Y, Kurokawa S, Maruyama T, Sasaki S, Kohri K, Hayashi Y.
  • 雑誌名: J Urol 181 ページ: 1330-1337
  • 査読あり
• [雑誌論文] Detection of ectopic ureteral insertion to vagina with hypoplastic ectopic kidney by computed tomography with three-dimensional imaging. (2009)
  • 著者名/発表者名: Iwatsuki S, Kojima Y, Imura M, Mizuno K, Kohri K, Hayashi Y.
  • 雑誌名: Urology 73 ページ: 505-506
  • 査読あり
• [雑誌論文] Laparoscopi corchiectomy and subsequent internal ring closure for extra-abdominal testicular nubbin in children. (2009)
  • 著者名/発表者名: Kojima Y, Mizuno K, Imura M, Kato T,Kohri K Hayashi Y.
  • 雑誌名: Urology 73 ページ: 515-519
  • 査読あり
• [雑誌論文] Gene transfer to sperm and testis : future prospects of gene therapy for male infertility. (2008)
  • 著者名/発表者名: Kojima Y, Kurokawa S, Mizuno K, Umemoto Y, Sasaki S, Hayashi Y, Kohri K.
  • 雑誌名: Curr Gene Ther 8 ページ: 121-34
  • 査読あり
• [雑誌論文] A case of azoospermia with Kippel-Feil anomaly. (2008)
  • 著者名/発表者名: Umemoto Y, Sasaki S, Kojima Y, Kaneko T, Yanai Y, Kohri K.
  • 雑誌名: Int J Urol 15 ページ: 188-9
  • 査読あり
• [雑誌論文] Upregulation of SOX9 in human SRY-negative XX males. (2008)
  • 著者名/発表者名: Kojima Y, Hayashi Y, Mizuno K, Sasaki S, Fukui Y, Koopman K, Morohashi K-I, Kohri K.
  • 雑誌名: Clin Endocrinol 68 ページ: 791-9
  • 査読あり
• [雑誌論文] Early orchiopexy improve the subsequent testicular development and spermatogenesis in the experimental cryptorchid rat model. (2008)
  • 著者名/発表者名: Mizuno K, Hayashi Y, Kojima Y, Kurokawa S, Sasaki S, Kohri K.
  • 雑誌名: J Urol 179 ページ: 1195-9
  • 査読あり
• [雑誌論文] No evidence of germline transmission by adenovirus-mediated gene transfer to mouse testes. (2008)
  • 著者名/発表者名: Kojima Y, Hayashi Y, Kurokawa S, Mizuno K, Sasaki S, Kohri K.
  • 雑誌名: Fertil Steril 89 ページ: 1448-54
  • 査読あり
• [雑誌論文] Simulated conditions of microgravity increases progesterone production in I-10cells of Leydig tumor cell line. (2008)
  • 著者名/発表者名: Kaneko T, Sasaki S, Umemoto Y, Kojima Y, Ikeuchi T, Kohri K.
  • 雑誌名: Int J Urol 15 ページ: 245-50
  • NAID: 10021277148
  • 査読あり
• [雑誌論文] Modified foreskin reconstruction for distal hypospadias and chordee without hypospadias. (2008)
  • 著者名/発表者名: Hayashi Y, Kojima Y, Mizuno K, Maruyama T, Tozawa K, Kohri K.
  • 雑誌名: Int J Urol 15 ページ: 646-8
  • NAID: 10021279123
  • 査読あり
• [雑誌論文] Usefulness of transcription factors Ad4BP/SF-1 and DAX-1 as immunohistologic markers for diagnosis of advanced adrenocortical carcinoma. (2008)
  • 著者名/発表者名: Kaneko T, Kojima Y, Umemoto Y, Sasaki S, Hayashi Y, Kohri K.
  • 雑誌名: Horm Res 70 ページ: 294-299
  • 査読あり
• [雑誌論文] (2008)
  • 著者名/発表者名: Kamisawa H, Kojima Y, Hayashi Y, Imura M, Mizuno K, Kohri K.Evaluation of preoperative testicular volume in Japanese children with unilateral cryptorchidism.
  • 雑誌名: Int Urol Nephrol 40 ページ: 977-81
  • 査読あり
• [雑誌論文] Achieving a natural glanular meatus for distal hypospadias with a narrow and shallow plate: tubularized incised plate versus modified Barcat repair. (2008)
  • 著者名/発表者名: Hayashi Y, Kojima Y, Mizuno K, Kurokawa S, Nakane A, Kohri k.
  • 雑誌名: Int J Urol 15 ページ: 616-20
  • NAID: 10021278995
  • 査読あり
• [雑誌論文] Gene transfer to sperm and testis : future prospects of gene therapy for male infertility (2008)
  • 著者名/発表者名: Kojima, et.al.
  • 雑誌名: Current Gene Therapy 8 ページ: 121-134
  • 査読あり
• [雑誌論文] No evidence of germline transmission by adenovirus-mediated gene transfer to mouse testes (2008)
  • 著者名/発表者名: Kojima, et.al.
  • 雑誌名: Fertility and Sterility 89 ページ: 1448-1454
  • 査読あり
• [雑誌論文] Upregulation of SOX9 in human SRY-negative XX males (2008)
  • 著者名/発表者名: Kojima, et.al.
  • 雑誌名: Clinical Endocrinology 68 ページ: 791-799
  • 査読あり
• [雑誌論文] Can a slit-like meatus be achieved with the V-incision sutured meatoplasty for onlay island flap hypospadias repair? (2007)
  • 著者名/発表者名: Hayashi Y, Kojima Y, Nakane A, Maruyama T, Kohri K.
  • 雑誌名: BJU Int 99 ページ: 1479-82
  • 査読あり
• [雑誌論文] Management of urethral calculi associated with hairballs after urethroplasty for severe hypospadias. (2007)
  • 著者名/発表者名: Hayashi Y, Yasui T, Kojima Y, Maruyama T, Tozawa K, Kohri K.
  • 雑誌名: Int J Urol 14 ページ: 161-3
  • NAID: 10018850021
  • 査読あり
• [雑誌論文] Influence for testicular development and histological peculiarity in the testes of flutamide-induced cryptorchid rat model. (2007)
  • 著者名/発表者名: Mizuno K, Hayashi Y, Kojima Y, Kurokawa S, Sasaki S, Kohri K.
  • 雑誌名: Int J Urol 14 ページ: 67-72
  • NAID: 10018693015
  • 査読あり
• [雑誌論文] Neo-modified Koyanagi technique for the single-stage repair of proximal hypospadias. (2007)
  • 著者名/発表者名: Hayashi Y, Kojima Y., Mizuno K. Nakane A., Kurokawa S., Maruyama T. Kohri K.
  • 雑誌名: J Pediatr Urol 3 ページ: 239-242
  • 査読あり
• [雑誌論文] Ventral based dartos flap for the prevention of the urethrocutaneous fistula urethroplasty. (2007)
  • 著者名/発表者名: Hayashi Y, Kojima Y, Nakane A,Kurokawa S, Tozawa K, Kohri K.
  • 雑誌名: Int J Urol 14 ページ: 725-728
  • NAID: 10019530165
  • 査読あり
• [雑誌論文] Influence for testicular development and histological peculiarity in the testes of flutamide-induced cryptorchid rat model (2007)
  • 著者名/発表者名: Mizuno K, Kojima Y, et. al.
  • 雑誌名: International Journal of Urology 14 ページ: 67-72
  • NAID: 10018693015
  • 査読あり
• [雑誌論文] Genes associated with the formation of germ cells from embryonic stem cells in cultures containing different glucose concentrations. (2006)
  • 著者名/発表者名: Mizuno K, Tokumasu A, Nakamura A, Hayashi Y, Kojima Y, Kohri K, Noce T.
  • 雑誌名: Mol Reprod Dev 73 ページ: 437-45
  • 査読あり
• [雑誌論文] Role of transcription factors Ad4BP/SF-1 and DAX-1 in steroidogenesis and spermatogenesis in human testicular development and idiopathic azoospermia. (2006)
  • 著者名/発表者名: Kojima Y., Sasaki S., Hayashi Y. Umemoto Y., Morohashi K-I., Kohri K.
  • 雑誌名: Int J Urol 13 ページ: 785-793
  • NAID: 10017612344
  • 査読あり
• [雑誌論文] Mathieu and Barcat repair with a V incision sutured meatiplasty for secondary hypospadias surgery. (2006)
  • 著者名/発表者名: Hayashi Y., Kojima Y., Mizuno K., Nakane A., Maruyama T., Kohri K.
  • 雑誌名: Int J Urol 13 ページ: 733-737
  • 査読あり
• [雑誌論文] Assessment of serum FSH level and testicular volume for prediction of future paternity in pubertal boys who had bilateral orchiopexy in childhood. (2006)
  • 著者名/発表者名: Kojima Y., Hayashi Y., Mizuno K., Kurokawa S., Sasaki S. Kohri K.
  • 雑誌名: J Urol 175 ページ: 2290-2294
  • 査読あり
• [雑誌論文] Pseudo-clitromegaly associated with prepubic sinus. (2006)
  • 著者名/発表者名: Hayase M., Kojima Y., Maruyama T., Hayashi Y., Kohri K.
  • 雑誌名: Int J Urol 13 ページ: 1031-1032
  • 査読あり
• [雑誌論文] Role of transcription factors Ad4BP/SF-1 and DAX-1 in steroidogenesis and spermatogenesis in human testicular development and idiopathic azoospermia. Int J Urol.13 : 783-791,2006. (2006)
  • 著者名/発表者名: Kojima et al.
  • 雑誌名: International Journal of Urology 13 ページ: 783-791
• [雑誌論文] Assessment of serum FSH level and testicular volume for prediction of future paternity in pubertal boys who had bilateral orchiopexy in childhood. J Urol, 175, 2290-2294, 2006. (2006)
  • 著者名/発表者名: Kojima et al.
  • 雑誌名: Journal of Urology 175 ページ: 2290-2294
• [雑誌論文] Long-term physical, hormonal and sexual outcome of males with disorders of sex development.
  • 著者名/発表者名: Kojima Y, Mizuno K, Nakane A, Kato T, Kohri K, Hayashi Y.
  • 雑誌名: J Pediar Surg. (in press)
  • 査読あり
• [雑誌論文] No evidence of germline transmission by adenovirus-mediated gene transfer to mouse testes
  • 著者名/発表者名: Kojima Y, et. al.
  • 雑誌名: Fetrility and Sterility (In press)
  • 査読あり
• [雑誌論文] Gene Transfer to Sperm and Testis: Future Prospects of Gene Therapy for Male Infertility
  • 著者名/発表者名: Kojima Y, et. al.
  • 雑誌名: Current Gene Therapy (In press)
  • 査読あり
• [学会発表] Gene Transfer to Mouse Testes by Electroporation and Its Influence on Spermatogenesis. (2008)
  • 著者名/発表者名: Umemoto Y, Sasaki S, Kojima Y, Kubota H, Kaneko T, Hayashi Y, Kohri K.
  • 学会等名: The 103rd American Urological Association
  • 発表場所: Orlando
• [学会発表] Identification of differential expressed genes associated with testicular descent using PCR-based suppressive subtractive hybridization and relationship to germ cell maturation (2008)
  • 著者名/発表者名: Mizuno K, Kojima Y, Kurokawa S, Kamisawa H, Imura M, Nakane A, Kato T, Maruyama T, Hayashi Y, Kohri K.
  • 学会等名: The 103rd American Urological Association
  • 発表場所: Orlando
• [学会発表] Distribution of Gene Expression on Genital Tubercles in the Hypospadiac Rat (2008)
  • 著者名/発表者名: Kurokawa S, Kojima Y, Mizuno K, Imura M, Hayashi Y, Kohri K.
  • 学会等名: The 103rd American Urological Association
  • 発表場所: Orlando
• [学会発表] Usefulness of MR fat-suppressed T2-weighted and diffusion-weighted imaging for the diagnosis of non-palpable testes (2008)
  • 著者名/発表者名: Kato T, Kojima Y, Shibata Y, Imura M, Mizuno K, Maruyama T, Hayashi Y, Kohri K,
  • 学会等名: The 103rd American Urological Association
  • 発表場所: Orlando
• [学会発表] Participation of apoptosis in the mechanism of dysfunction of spermatogenesis after vasectomy. (2007)
  • 著者名/発表者名: Umemoto Y, Sasaki S, Hayase M, Kojima Y, Kubota Y, Kohri K
  • 学会等名: 29th Congress of the Societe Internationale d'Urologie
  • 発表場所: Paris
• [学会発表] Evaluation of the long-term function outcome with uroflowmetry : The meatal-based flip-flap repair for distal hypospadias. (2007)
  • 著者名/発表者名: Imura M, Hayashi Y, Kojima Y, Kurokawa S, Nakane A, Mizuno K, Maruyama T, Iwase Y, Kohri K
  • 学会等名: 29th Congress of the Societe Internationale d'Urologie
  • 発表場所: Paris
• [学会発表] Open pyeloplasty with a minimally invasive incision in children : comparison of skin incision size. (2007)
  • 著者名/発表者名: Nakane A, Hayashi Y, Mizuno K, Kojima Y, Maruyama T, Kohri K
  • 学会等名: 29th Congress of the Societe Internationale d'Urologie
  • 発表場所: Paris
• [学会発表] No evidence of germline transmission by adenovirus-mediated gene transfer to mouse testes. (2007)
  • 著者名/発表者名: Kojima Y., Hayashi Y., Kurokawa S., Mizuno K., Sasaki S., Kohri K.
  • 学会等名: The 102nd American Urological Association
  • 発表場所: Anaheim
• [学会発表] Gene expression profiling of urethral development in the hypospadiac rat. (2007)
  • 著者名/発表者名: Kurokawa S., Kojima Y., Mizuno K., Hayashi Y., Kohri K.
  • 学会等名: The 102nd American Urological Association
  • 発表場所: Anaheim
• [学会発表] Clitoral hypertrophy after nuro-vascular bundle preserved reduction clitoroplasty in congenital adrenal hyperplasia. (2007)
  • 著者名/発表者名: Maruyama T., Hayashi Y., Kojima Y., Kohri K.
  • 学会等名: The 102nd American Urological Association
  • 発表場所: Anaheim
• [学会発表] No evidence of germline transmission by adenovirus-mediated gene transfer to mouse testes (2007)
  • 著者名/発表者名: Kojima Y, et. al.
  • 学会等名: The 102nd American Urological Association
  • 発表場所: Anaheim
• [学会発表] Correlation between clinical findings and expression of transcription factors and growth factors implicated in sexual differentiation and steroidogenesis in testicular tissue of XX sex reversal patients. (2006)
  • 著者名/発表者名: Kojima Y., Hayashi Y., Sasaki S., Kohri K.:
  • 学会等名: The 101th American Urological Association
  • 発表場所: Atlanta
• [図書] Andrology for clinician (2006)
  • 著者名/発表者名: Kojima Y., Sasaki S, Kohri K.
  • 出版者: Therapeutic options: Current research and future prospects for gene therapy in andrology. Hargreave T, Comhaire F, Schill W-B (eds) In