着床機能異常を検出する生理的パラメーターの創出

2009 Fiscal Year Annual Research Report

• Project/Area Number: 21390453
• Research Institution: Osaka University
• Principal Investigator: 木村 正 大阪大学, 医学系研究科, 教授 (90240845)
• Co-Investigator(Kenkyū-buntansha): 細野 剛良 大阪電気通信大学, 医療福祉工学部, 教授 (60294104) ; 筒井 建紀 大阪大学, 医学系研究科, 講師 (00294075) ; 香山 晋輔 大阪大学, 医学系研究科, 助教 (30528005) ; 中村 仁美 大阪大学, 医学部付属病院, 特任臨床検査技師 (80467571)
• Keywords: 着床 / 不妊症 / 妊娠高血圧症候群 / reterm premature rapture of membrane (pPROM) / intrauterine growth restiriction (IUGR) / 血管透過性 / インピーダンス / pH

Research Abstract

妊娠に関連する病態は主に妊娠後半におこるが、その原因は妊娠のきわめて初期の段階である着床過程にあると考えられている。つまり、不妊症だけでなく、妊娠中におこる病態、妊娠高血圧症候群やpreterm premature rapture of membrane (pPROM), intrauterine growth restiriction (IUGR)等はこの妊娠現像の早期におこる看床現象の何らかの異常により引き起こされると考えられている。そこで本研究では、効率のよい不妊治療、および妊娠に係わる病態の治療に反映する事を目的として、胎盤形成までの広義の着床現象に対してこれをリアルタイムに低侵襲に評価することができるシステムの構築をマウスを用いて行った。マウス着床部位において、血管透過性が上昇している事が知られている。そこで、生体色素であるインドシアグリーンを静脈より注入して、これを870nmの励起波長のモノクロCCD(近赤外線)カメラで体外から検出する事ができるというシステムを用いて、子宮の血管透過性を体表から検出できるようにシステムの構築を行った。さらに、子宮腔内のpH、電位差および電気抵抗(インピーダンス)をモニタリングできるシステムの構築を行った。インピーダンスに関しては今年度は膣のインピーダンスの測定を行った。膣インピーダンスは個々の測定値のばらつきが小さく、着床期にむけてインピーダンスは低下しており、これが有効なパラメーターと成り得る事が示唆された。来年度はこのプローブをさらに改良を行い、子宮腔内のインピーダンスを直接検出できるようにして検討を行う。子宮腔内の生体内pHおよび電位差の測定のために、直径0.3mmのガラスコートアンチモン電極を作製した。pHについては妊娠周期において差を認められなかったが、電位差については、ばらつきが比較的小さく、また、着床不全マウスモデルにおいて電位差に変化が認められ、子宮腔内の生体内電位差がパラメーターとして有効である事が示唆された。

Research Products

• [Journal Article] Concurrent weekly nedaplatin, external beam radiotherapy and high-dose rate brachytherapy in patients with FIGO stage IIIB cervical cancer : A comparison with a cohort treated by radiotheraphy alone (2010)
  • Author(s): Mabuchi, S., Ugaki, H., Isohashi, F., Yoshioka, Y., Temma, K., Yoda-Hashimoto, N., Takeda, T., Yamamoto, T., Yoshino, K., Nakajima, R., Kuragaki, C., Morishige, K., Enomoto, T., Inoue, T., Kimura, T.
  • Journal Title: Gynecologic and Obstetric Investigation Volume: 69 Pages: 224-232
  • Peer Reviewed
• [Journal Article] Temporal and spatial expression of tumor-associated antigen RCAS1 in pregnant mouse uterus. (2010)
  • Author(s): Tskitishvili, E., Nakamura, H., Kinugasa-Taniguchi, Y., Kanagawa, T., Kimura, T., Tomimatsu, T., Shimoya, K.
  • Journal Title: Int J Gynecol Cancer. Volume: 63 Pages: 137-143
  • Peer Reviewed
• [Journal Article] Spinal subarachnoid hematoma following spinal anesthesia in a patient with HELLP syndrome. (2010)
  • Author(s): Koyama, S., Tomimatsu, T., Kanagawa, T., Sawada, K., Tsutsui, T., Kimura, T., Chang, YS., Wasada, K., Imai, S., Murata, Y.
  • Journal Title: Int J Obstet Anesth. Volume: 19 Pages: 87-91
  • Peer Reviewed
• [Journal Article] Oxidative stress-induced S100B protein from placenta and amnion affects soluble Endoglin release from endothelial cells. (2010)
  • Author(s): Tskitishvili, E., Sharentuya, N., Temma-Asano, K., Mimura, K., Kinugasa-Taniguchi, Y., Kanagawa, T., Fukuda, H., Kimura, T., Tomimatsu, T., Shimoya, K.
  • Journal Title: Mol Hum Reprod. Volume: 16 Pages: 188-199
  • Peer Reviewed
• [Journal Article] A case of complete hydatidiform mole with co-existent fetus ; conclusive diagnosis of androgenesis of the molar placenta by variation of paternal acrocentric short arm (2010)
  • Author(s): Koyama, S., Tomimatsu, T., Sawada, K., Kanagawa, T., Isobe, A., Kinugasa, Y., Tsutsui, T., Kimura T.
  • Journal Title: America Journal of Perinatology Volume: 27 Pages: 143-149
  • Peer Reviewed
• [Journal Article] 妊娠子宮局所におけるマクロファージの役割 (2010)
  • Author(s): 中村仁美、木村正
  • Journal Title: 医学のあゆみ Volume: 233巻(In press)
  • Peer Reviewed
• [Journal Article] Spinal subarachnoid hematoma following spinal anesthesia in a patient with HELLP syndrome (2009)
  • Author(s): Koyama, S., Tomimatsu, T., Kanagawa, T., Sawada, K., Tsutsui, T., Kimura, T., Chang YS., Wasada. K., Imai, S., Murata, Y.
  • Journal Title: Int Obestet Anesth Volume: 19 Pages: 87-91
  • Peer Reviewed
• [Journal Article] Evidence that oxytocin exerts anxiolytic effects via oxytocin receptor expressed in serotonergic neurons in mice (2009)
  • Author(s): Yoshida, M., Takayanagi, Y., Inoue, K., Kimura, T.,, Young, L.J, Onaka, T., Nishimori, K.
  • Journal Title: Journal of Neuroscience Volume: 29 Pages: 2259-2271
  • Peer Reviewed
• [Journal Article] Uterine cervical carcinoma : preoperative staging 3.0-T MR imaging-comparison with 1.5-T MR imaging (2009)
  • Author(s): Hori, M., Kim, T., Murakami, T., Imaoka, I., Onishi, H., Tomoda, K., Tsutsuui, T., Enomoto, T., Kimura, T., Nakamura, H.
  • Journal Title: Radiology Volume: 251 Pages: 96-104
  • Peer Reviewed
• [Journal Article] The activity of carboplatin and paclitaxel for recurrent cervical cancer after definitive radiotherapy (2009)
  • Author(s): Mabuchi, S., Morishige, K., Fujita, M., Tsutsui, T., Sakata, M., Enomoto, T., Kimura, T.
  • Journal Title: Gynecologic Oncology Volume: 113 Pages: 200-204
  • Peer Reviewed
• [Journal Article] Amniotic fluid 'sludge' detected in patients with subchorionic hematoma : a report of two cases (2009)
  • Author(s): Tskitishvili, E, Tomimatsu, T., Kanagawa, T., Sawada, Y., Kinugasa, Y., Mimura, K., Kimura, T.
  • Journal Title: Ultrasouond Obstet Gynecol Volume: 33 Pages: 484-486
  • Peer Reviewed
• [Journal Article] Peripheral quantitative computed tomography is useful to monitor response to alendronate therapy in postmenopausal women (2009)
  • Author(s): Sawada, K., Morishige, K., Nishio, Y., Hayakawa, J., Mabuchi, S., Iosbe, A., Ogata, S., Sakata, M., Ohmichi, M., Kimura, T.
  • Journal Title: J Bone Miner Metab Volume: 27 Pages: 175-181
  • Peer Reviewed
• [Journal Article] Cesarean scar pregnancies succseefully treated with methotrexate (2009)
  • Author(s): Muraji, M., Mabuchi, S., Hisamoto, K., Muranishi, M., Kanagawa, T., Nishio, Y., Kimura, T.
  • Journal Title: Acta Obstetricia et Gynecologica Scandinavica Volume: 88 Pages: 720-723
  • Peer Reviewed
• [Journal Article] Wilms' tumor 1 (WT1) peptide immunotherapy for gynecological malignancy (2009)
  • Author(s): Ohno, S., Kyo, S., Myojo, S., Dohi, S., Ishizaki, J., Miyamoto, K-I., Morita, S., Sakamoto, J-I., Enomoto, T., Kimura, T., Oka, Y., Tsuboi, A., Sugiyama, H., Inoue, M.
  • Journal Title: Anticancer Research Volume: 29 Pages: 4779-4784
  • Peer Reviewed
• [Journal Article] A case of recurrent cesarean scar pregnancy (2009)
  • Author(s): Mabuchi, S., Kawase, C., Muraji, M., Kanagawa, T., Kimura, T.
  • Journal Title: Acta Obstetricia et Gynecologica Scandinavica Volume: 88 Pages: 1059-1060
  • Peer Reviewed
• [Journal Article] Metal transcription factor-1 is involved in hypoxia-dependent regulation of placenta growth factor in trophoblast-derived cells (2009)
  • Author(s): Nishimoto, F., Sakata, M., Minekawa, R., Okamoto, Y., Miyake, A., Isobe, A., Yamamoto, T., Takeda, T., Ishida, E., Sawada, K., Morishige, K-I., Kimura, T.
  • Journal Title: Endocrinology Volume: 150 Pages: 1801-1808
  • Peer Reviewed
• [Journal Article] Up-regulation of alpha5-integrin by E-cadherin loss in hypoxia and its key role in the migration of extravillous trophoblast cells during early implantation. (2009)
  • Author(s): Arimoto-Ishida, E., Sakata, M., Sawada, K., Nakayama, M., Nishimoto, F., Mabuchi, S., Takeda, T., Yamamoto, T., Isobe, A., Okamoto, Y., Lengyel, E., Suehara, N., Morishige, K., Kimura, T.
  • Journal Title: Endocrinology. Volume: 150 Pages: 4306-15
  • Peer Reviewed
• [Journal Article] Calcineurin/NFAT pathway : a novel regulator of parturition (2009)
  • Author(s): Tabata, C., Ogita, K., Sato, K., Nakamura, H., Negoro, H., Kumasawa, K., Temma-Asano, K., Tsutsui, T., Nishimori, K., Kimura, T.
  • Journal Title: American Journal of Reproductive Immunology Volume: 62 Pages: 44-50
  • Peer Reviewed
• [Journal Article] MR Imaging of endometrial carcinoma for preoperative staging at 3.0 T : comparison with imaging at 1.5 T (2009)
  • Author(s): Hori, M., Kim, T., Murakami, T., Imaoka, I., Onishi, H., Nakamoto, A., Nakaya, Y., Tomoda, K., Tsutsui, T., Enomoto, T., Kimura, T., Nakamura, H.
  • Journal Title: Journal of Magnetic Resonance Imaging Volume: 30 Pages: 621-630
  • Peer Reviewed
• [Journal Article] mTOR is a promising therapeutic target both in cisplatin-sensitive and cisplatin-resistant clear cell carcinoma of the ovary. (2009)
  • Author(s): Mabuchi, S., Kawase, C., Altomare, DA., Morishige, K., Sawada, K., Hayashi, M., Tsujimoto, M., Yamoto, M., Klein-Szanto, AJ., Schilder, RJ., Ohmichi, M., Testa, JR., Kimura, T.
  • Journal Title: Clin Cancer Res. Volume: 15 Pages: 5404-13
  • Peer Reviewed
• [Journal Article] Postoperative concurrent nedaplatin-based chemoradiotherapy imprves survival in early-stage cervical cancer patients with adverse risk factors. (2009)
  • Author(s): Mabuchi, S., Morishige, K., Isohashi, F., Yoshioka, Y., Takeda, T., Yamamoto, T., Yoshino, K., Enomoto, T., Inoue, T., Kimura, T.
  • Journal Title: Gynecologic Oncology Volume: 115 Pages: 482-487
  • Peer Reviewed
• [Journal Article] Postpartum outcome of cervical intraepithelial neoplasia in pregnant women determined determined b route of delivery (2009)
  • Author(s): Ueda, Y., Enomoto, T., Miyatake, T., Yoshino, K., Fujita, M., Miyake, T., Fujiwara, K., Muraji, M., Kanagawa, T., Kimura, T.
  • Journal Title: Reproductive Science Volume: 16 Pages: 1034-1039
  • Peer Reviewed
• [Journal Article] Fasudil inhibits lysophosphatidic acid-induced invasiveness of human ovarian cancer cells. (2009)
  • Author(s): Ogata, S., Morishige, K., Sawada, K., Hashimoto, K., Mabuchi, S., Kawase, C., Ooyagi, C., Sakata, M., Kimura, T.
  • Journal Title: Int J Gynecol Cancer. Volume: 19 Pages: 1473-1480
  • Peer Reviewed
• [Journal Article] 妊娠子宮局所におけるマクロファージの役割 (2009)
  • Author(s): 中村仁美、香山晋輔、谷口武、荻田和秀、熊澤恵一、張慶、筒井建紀、古山将康、杉野法広、田村博史、金田安史、木村正
  • Journal Title: 生殖内分泌学会雑誌 Volume: 14巻 Pages: 35-40
  • Peer Reviewed
• [Presentation] Endometrial Stat3 activation and implantation failure (2009)
  • Author(s): Kimura, T
  • Organizer: IUPS Satellite Symposium on Endometrial Receptivity and Blastocyst Implantation
  • Place of Presentation: Inamori Hall, Kyoto University
  • Year and Date: 2009-07-25
• [Presentation] Mouse model of human infertility : transient and local inhibition of endo metrial STAT-3 activation results in implantation failure (2009)
  • Author(s): Kimura, T.
  • Organizer: 5^<th> International Conference on the Female Reproductive Tact
  • Place of Presentation: Frauenchiemsee, Germany
  • Year and Date: 2009-05-17