神戸大学大学院医学研究科腎泌尿器科学分野

Division of Urology, Department of Surgery Related, Kobe University Graduate School of Medicine

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研究グループ

男子不妊症グループ

臨床研究

不妊症は約10-15%の頻度で認められ、その約半数は男性側要因を含む。昨今、生殖医療技術の臨床応用がすすみART (assisted reproductive technology) による妊娠、出産例は増加している。ART時代にあって、従来よりおこなわれてきた精索静脈瘤に対する内精静脈結紮術、精路閉塞に対する再建術などの男性不妊症治療の選択肢もTime-to-pregnancy, cost-effectivenessの観点から患者個々の背景、具体的にはパートナーの年齢や不妊症の原因となる疾患の有無などにより複雑となっている。停留精巣やSertoli-cell-only症候群などによる精子形成不全に対しても近年ひろくmicrodissection をもちいたTESE (testicular sperm extraction) やICSI (intracytoplasmic sperm injection) により挙児を得る機会が増え、我々も積極的に取り組んでいる。また、クラインフェルター症候群、Y染色体微小欠失、先天性両側精管欠損症におけるCFTR遺伝子異常などの症例においても児をうることが可能となった。しかし、これら症例では次世代へ伝播するなどの問題についても充分検討される必要があり今後の課題である。

  • Yamaguchi K, Ishikawa T, Chiba K, Fujisawa M. Assessment of possible effects for testosterone replacement therapy in men with symptomatic late-onset hypogonadism. Andrologia, in press, 2010
  • Hashimoto H, Ishikawa T, Goto S, Kokeguchi S, Fujisawa M, Shiotani M. The effects of severity of oligozoospermia on Intracytoplasmic Sperm Injection (ICSI) cycle outcome. Syst Biol Reprod Med 56: 91-5, 2010
  • Ishikawa T, Yamaguchi K, Chiba K, Takenaka A, Fujisawa M. Serum hormones in patients with nonobstructive azoospermia after microdissection testicular sperm extraction. J Urol 182:1495-9, 2009
  • Chiba K, Ishikawa T, Yamaguchi K, Fujisawa M. The efficacy of adult orchidopexy as a treatment of male infertility: our experience of 20 cases. Fertil Steril 92: 1337-9, 2009
  • Ishikawa T, Nose R, Yamaguchi K, Chiba K, Fujisawa M. Learning curves of microdissection testicular sperm extraction for nonobstructive azoospermia. Fertil Steril 2009
  • Ishikawa T, Shiotani M, Izumi Y, Hashimoto H, Kokeguchi S, Goto S, Fujisawa M. Fertilization and pregnancy using cryopreserved testicular sperm for intracytoplasmic sperm injection with azoospermia. Fertil Steril 92: 174-9, 2009
  • Kondo Y, Ishikawa T, Yamaguchi K, Fujisawa M. Predictors of Improved Seminal Characteristics by Varicocele Repair. Andrologia 41: 20-3, 2009.
  • Sakamoto Y, Ishikawa T, Yamaguchi K, Kondo Y, Fujisawa M. The assessment of oxidative stress in varicocele patients. BJU Int 101:1547-52, 2008
  • Ishikawa T, Yamaguchi K, Kondo Y, Takenaka A, Fujisawa M. Metabolic syndrome in men with Klinefelter syndrome. Urology 71:1109-13, 2008.
  • Ishikawa T, Kondo Y, Yamaguchi K, Sakamoto Y, Takenaka A, Fujisawa M. Effect of varicocelectomy on nonobstructive azoospermic and severe oligospermic patients. BJU Int 101: 216-8, 2008
  • Ishikawa T, Fujioka H, Ishimura T, Takenaka A, Fujisawa M. Increased testicular 8-hydroxydeoxyguanosine (8-OHdG) in patients with varicocele. BJU Int 100: 863-6, 2007
  • Ishikawa T, Kondo Y, Yamaguchi K, Ooba T, Sakamoto Y, Takenaka A, Fujisawa M. An unusual reciprocal X-autosome translocation in an infertile azoospermic patient. Fertil Steril 88: 705 e15-7, 2007
  • Ishikawa T, Ooba T, Kondo Y, Yamaguchi K, Fujisawa M. Assessment of gonadotropin therapy in male hypogonadotropic hypogonadism. Fertil Steril 88: 1697-9, 2007 .
  • Ishikawa T, Fujisawa M, Tapanainen JS. Screening of FSH receptor gene mutation (C566T) in azoospermic men in Japan . Arch Androl 52: 15-9, 2006
  • Ishikawa T, Fujisawa M. Effect of age and grade on surgery for patients with varicocele. Urology 65: 768-72, 2005
  • Ishikawa T, Kamidono S, Fujisawa M. Fertility after high-dose chemotherapy for testicular cancer. Urology 63: 137-40, 2004
  • Ishikawa T, Fujioka H, Fujisawa M. Clinical and hormonal findings in testicular maturation arrest. BJU Int 94: 1314-6, 2004 .
  • Fujisawa M, Ishikawa T. Soluble forms of Fas and Fas ligand concentrations in the seminal plasma of infertile men with varicocele. J Urol 170: 2363-5, 2003.

基礎研究

精巣機能調節機構の解明は特発性男性不妊症の病態の解明と治療法の開発に寄与するものと考えられる。視床下部-下垂体-精巣軸ではcytokine、growth factorの精巣機能調節に及ぼす影響、精巣内ではGerm cell、Sertoli cell、Leydig cellの細胞間調節に着目し、これまでに多くの成果を挙げている。またspermatogenesis、steroidogenesisにおける精巣機能調節機構を解明する手法として造精機能障害モデルや分離培養細胞をもちいて精巣内遺伝子導入を試み、遺伝子発現の誘導、抑制の効果を調べる研究にも取り組んでいる。

  • Hashimoto H, Ishikawa T, Yamaguchi K, Kondo Y, Shiotani M , Fujisawa M. The expression and localization of vascular endothelial growth factor in ischemia-reperfusion injury of testis. Andrologia 41: 216-21, 2009
  • Haraguchi T, Ishikawa T, Yamaguchi K, Kondo Y, Fujisawa M. Cyclin and protamine as prognostic molecular marker for testicular sperm extraction in azoospermic patients. Fertil Steril in press, 2008.
  • Yamaguchi K, Ishikawa T, Kondo Y, Fujisawa M. Cisplatin Regulates Sertoli Cell Expression of Transferrin and Interleukins. Mol Cell Endocrinol 283: 68-75, 2008.
  • Kondo Y, Ishikawa T, Yamaguchi K, Yada T, Fujisawa M. Oral Administration of Tetrahydrobiopterin Attenuates Testicular damage by Reducing Nitric Oxide Synthase Activity in a Cryptorchid Mouse Model. J Androl 29: 153-63, 2008.
  • Ooba T, Ishikawa T, Yamaguchi K, Kondo Y, Fujisawa M. 2007 Expression and distribution of laminin chains in the testis for the patients with azoospermia. J Androl 29:147-52, 2008.
  • Ishikawa T, Fujioka H, Ishimura T, Takenaka A, Fujisawa M. Expression of leptin and leptin receptor in the testis of fertile and infertile patients. Andrologia. 39: 22-7, 2007.
  • Ishikawa T, Fujioka H, Ishimura T, Takenaka A, Fujisawa M. Ghrelin Expression in human testis and serum testosterone level. J Androl. 28: 320-4 2007.
  • Ishikawa T, Morris PL. Interleukin-1β signals through a cJun-N-terminal kinase (JNK)-dependent inducible nitric oxide synthase and nitric oxide production pathway in Sertoli epithelial cells. Endocrinology. 147: 5424-30, 2006.
  • Ishikawa T, Morris PL. A multistep kinase-based sertoli cell autocrine-amplifying loop regulates prostaglandins, their receptors, and cytokines. Endocrinology. 147: 1706-16, 2006
  • Ishikawa T, Hwang K, Lazzarino D, Morris PL. Sertoli cell expression of steroidogenic acute regulatory protein-related lipid transfer 1 and 5 domain-containing proteins and sterol regulatory element binding protein-1 are interleukin-1β regulated by activation of c-Jun N-terminal kinase and cyclooxygenase-2 and cytokine induction. Endocrinology. 146: 5100-11, 2005.
  • Ishikawa T, Kondo Y, Goda K, Fujisawa M. Overexpression of endothelial nitric oxide synthase in transgenic mice accelerates testicular germ cell apoptosis induced by experimental cryptorchidism. J Androl. 26: 281-8, 2005.