Gene transfer to sperm and testis : future prospects of gene therapy for male infertility.

• Project/Area Number: 18689039
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Urology
• Research Institution: Nagoya City University
• Principal Investigator: KOJIMA Yoshiyuki Nagoya City University, 大学院・医学研究科, 講師 (60305539)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥13,780,000 (Direct Cost: ¥10,600,000、Indirect Cost: ¥3,180,000); Fiscal Year 2008: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2007: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2006: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
• Keywords: 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

Research Abstract

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。

Research Products

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