生殖内分泌学・周産期医学研究室

生殖内分泌研究

生殖現象は生命を維持するうえで基軸となる分野であり、内分泌臓器の精緻な相互作用によって制御されています。生殖機能の調節において、性ホルモンや生理活性物質の情報伝達に関わるメカニズムは未だ解明されるべき点が山積しております。

私どもは、生殖内分泌・不妊症分野におきまして、「子宮内膜症の病態解析」や「卵巣顆粒膜細胞や絨毛細胞における増殖因子や炎症性サイトカインの役割」に関する研究を行っています。

昨今の医師の研究分野離れが危惧されておりますが、地道な研究活動を確実に業績として実らせ、継続的に新知見を世界に向けて発信することは、医学の発展に貢献するものと考えております。

ヒト子宮内膜症病変およびマウス内膜症モデルによる基礎研究

  1. 子宮内膜症の病態形成における炎症性サイトカインの役割
    子宮内膜症患者の腹水に含まれるマクロファージや、子宮内膜症病変から産生される腫瘍壊死因子(TNFα)をはじめとする炎症性サイトカインの産生バランスが内膜症の病態形成に重要であることを報告しました。また、リポポリサッカライドがCOX-2およびプロスタグランジン発現を介した子宮内膜症細胞の接着・増殖を促し、子宮内膜症の腹腔内炎症を促進することを示しました。
  2. 子宮内膜症細胞が有するアポトーシス抵抗性の解明
    子宮内膜症細胞は類腫瘍的性格をもち、アポトーシス抵抗性を有することが知られています。サバイビンをはじめとする抗アポトーシス因子(IAP)が、子宮内膜症の病態形成に重要な役割を有することを明らかにしました。
  3. 新規薬剤による子宮内膜症治療の探索
    副作用の少ない漢方薬や薬用ハーブが、子宮内膜症モデルマウスにおける腫瘍縮小効果をもつことを明らかにしました。現在も、分子標的薬剤、シグナル伝達阻害剤および植物フラボノイドや、選択的エストロゲン受容体調節薬など、子宮内膜症に対する新規薬物治療の可能性を模索しています。
  4. 生殖器官における性ホルモン受容体の機能解析
    米国NIEHS/NIH等の協力により、子宮内膜症におけるエストロゲン受容体の機能解析や、卵胞発育・排卵過程における役割に関して研究しています。

周産期研究

当院は鳥取県の総合周産期母子医療センターであることから、重症な周産期症例を扱っており、一つ一つの症例を詳細に検討することで生じる疑問を研究の基盤としています。日本周産期新生児学会や日本超音波医学会の専門医、臨床遺伝専門医を取得することを目指して臨床研究に取り組んでいます。

  1. 子宮内膜症および子宮腺筋症による産科合併症の発症リスクに関する疫学的研究
  2. 妊娠初期にみつかる甲状腺機能異常による産科合併症リスクに関する前向き研究
  3. 胎児心エコー検査の診断精度と周産期予後に関する研究
写真 | 活動風景

業績

2023年

A nationwide survey of the use of the laparoscopic power morcellator.
Hiraike O, Koga K, Taniguchi F, Harada T, Takeshita T, Shiota M, Osuga Y:Laparoscopic power morcellator Research Committee in Japan Society of Gynecologic and Obstetric Endoscopy and Minimally Invasive Therapy( JSGOE).
J Obstet Gynaecol Res 49(2):682-690, 2023
Increased chemokine ligand 26 expression and its involvement in epithelial-mesenchymal transition in the endometrium with adenomyosis.
Ikebuchi A, Osaki M, Wada I, Nagata H, Nagira K, Azuma Y, Okada F, Harada T, Taniguchi F
J Gynecol Obstet Hum Reprod 52(9): 18 Aug 2023
Huge Leiomyomas Arising from Bilateral Uterine Remnants in a Mayer–Rokitansky-Küster-Hauser Syndrome Patient with Coexisting Myotonic Dystrophy Type 1: A Case Report and Literature Review
Azuma Y, Yamamoto K, Matsumoto M, Nagata H, Wada I, Miyamoto K, Taniguchi F
Case Rep Obstet Gynecol: Epub 2023 Aug 28
The Asian Society of Endometriosis and Adenomyosis guidelines for managing adenomyosis.
Harada T, Taniguchi F, Guo SW, Choi YM, Biberoglu KO, Tsai SS, Alborzi S, Al-Jefout M, Chalermchokcharoenkit A, Sison-Aguilar AG, Fong YF, Senanayake H, Popov A, Hestiantoro A, Kaufman Y.
Reprod Med Biol. 2023 Sep 10;22(1):e12535.
Role of tenascin-C in lesion formation in early peritoneal endometriosis.
Maako Moriyama, Kazuomi Nakamura, Hiroki Nagata, Ikumi Wada, Kei Nagira, Yukihiro Azuma, Eri Sato, Tasuku Harada, Fuminori Taniguchi
F&S Science, 2023, In press

2022年

Relugolix, an oral gonadotropin-releasing hormone receptor antagonist, reduces endometriosisassociated pain compared with leuprorelin in Japanese women:a phase 3, randomized,double-blind, noninferiority study.
Harada T, Osuga Y, Suzuki Y, Fujisawa M, Fukui M, Kitawaki J.
Fertil Steril 117(3):583-592, 2022
Tracing location by applying emerald luciferase in an early phase of murine endometriotic lesion formation.
Wibisono H, Nakamura K, Taniguchi F, Seno M, Morimoto K, Yoshimura Y, Harada T.
Exp Anim 71(2):184-192, 2022
Bleeding patterns of women with heavy menstrual bleeding or dysmenorrhea using the levonorgestrel-releasing intrauterine system:results from a real-world observational study in Japan( J-MIRAI).
Kitawaki J, Akira S, Harada T, Maeda N, Momoeda M, Ota I, Murakami T, Sunaya T, Hirano K.
Eur J Contracept Reprod Health Care 27(4):300-307, 2022
Quality of life of Japanese dysmenorrhea/heavy menstrual bleeding patients treated with levonorgestrel intrauterine delivery system in a real-world setting.
Momoeda M. Akira S, Harada T, Kitawaki J, Maeda N, Ota I, Yoshihara K, Takahashi N.
Adv Ther 39(8):3616-3634, 2022
Real-world outcomes of the levonorgestrel-releasing intrauterine system for heavy menstrual bleeding or dysmenorrhea in Japanese patients:A prospective observational study( J-MIRAI).
Harada T, Ota I, Kitawaki J, Momoeda M, Maeda N, Akira S, Umeyama M, Sunaya T, Hirano K.
Contraception 115:22-28, 2022
Clinical practice guidelines for endometriosis in Japan( The 3rd edition).
Harada T, Taniguchi F, Kitajima M, Kitawaki J, Koga K, Momoeda M, Mori T, Murakami T, Narahara H, Osuga Y, Yamaguchi K.
J Obstet Gynaecol Res 48(12):2993-3044, 2022

2021年

Harada T, Mikio M. Efficacy of cyclic and extended regimens of ethinylestradiol 0.02 mg -levonorgestrel 0.09 mg for dysmenorrhea: A placebo-controlled, double-blind, randomized trial. Reprod Med Biol. 2021 Feb. doi: 10.1002/rmb2.12373
Taniguchi F, Hermawan Wibisono, Yin Mon Khine, Tasuku H. Animal models for research on endometriosis. Front Biosci (Elite Ed). 2021: 13: 37-53.
Osaku D, Taniguchi F, Komatsu H, Harada T. Calcified ovarian fibromas complicated with basal cell nevus syndrome: A Case Report. Gynecol Minim Invasive Ther. 2021.

2020年

Taniguchi F, Yohei T, Ikuko O, Emiko Y, Hiroaki K, Yukihiro A, Eri S, Yusuke E, Hiroshi S, Tasuku H. Efficacy of Tokishakuyakusan add-on therapy with low-dose oral contraceptive pills on endometriosis patients with dysmenorrhea. J Obstet Gynaecol Res. 2020 Nov. doi: 10.1111/jog.14424
Miyamoto K, Hiroaki K, Yohei N, Satoru T, Masako S, Daiken O, Fuminori T, Tasuku H, Yasunobu K. Changes in serum D-dimer level and effect of enoxaparin sodium after a cesarean section: a retrospective study. J Matern Fetal Neonatal Med. 2020 Feb. doi: 10.1080/14767058.2020.1725884

2019年

Nagira K. Fuminori T, Kazuomi N, Yohei T, Naoko T, Yin Mon Khine, Tasuku H. Tokishakuyakusan, a Kampo medicine, attenuates endometriosis-like lesions and hyperalgesia in murine with endometriosis-like symptoms. Am J Reprod Immunol. 2019 Nov. doi: 10.1111/aji.13182
Nagata H, Hiroaki K, Yohei N, Satoru T, Masako S, Tasuku H, Yasunobu K. Comparison of Total Laparoscopic Hysterectomy with Abdominal Total Hysterectomy in Patients with Benign Disease: A Retrospective Cohort Study. Yonago Acta Med. 2019 Oct. doi: 10.33160/yam.2019.11.002
Harada T, Fuminori T, Hiroki A, Youichi K, Yuki I, Kunihiko H, Tasuku H, Japan Environment and Children's Study Group. Adverse obstetrical outcomes for women with endometriosis and adenomyosis: A large cohort of the Japan Environment and Children's Study. PLoS One. 2019 Aug. doi: 10.1371/journal.pone.0220256
Taniguchi F, Ikuko O, Yumiko I, Toshiko T, Yukiko T, Yorie O, Hiroko K, Yusuke E, Hiroshi S, Hisashi N, Yukihiro A, Tasuku H. The efficacy and safety of dydrogesterone for treatment of dysmenorrhea: An open-label multicenter clinical study. J Obstet Gynaecol Res. 2019 Jan. doi: 10.1111/jog.13807
Izawa M, Fuminori T, Tasuku H. GATA6 expression promoted by an active enhancer may become a molecular marker in endometriosis lesions. Am J Reprod Immunol. 2019 Jan

2018年

Taniguchi F, Osamu W H, Tetsuya H, Hiroto T, Hirotaka M, Mari K, Jun K, Ichiro U, Juichiro S, Keisuke K, Toshiyuki T, Tasuku H, Surgical Outcome Research Committee in JSGOE. J Obstet Gynaecol Res. 2018 Nov. doi: 10.1111/jog.13774
Yin Mon Khine, Fuminori T, Kei N, Kazuomi N, Tetsuya O, Mitsuhiko O, Tasuku H. New insights into the efficacy of SR-16234, a selective estrogen receptor modulator, on the growth of murine endometriosis-like lesions. Am J Reprod Immunol. 2018 Nov. doi: 10.1111/aji.13023
Harada T, Naoaki K, Osamu I, Tomohiko I, Minoru I, Yukiko K, Hidekazu S, Tatsuya H, Osamu W H, Fuminori T, Ethics Committee in Japan Society of Reproductive Medicine. Guideline for cryopreservation of unfertilized eggs and ovarian tissues in Japan Society of Reproductive Medicine: Ethics Committee in Japan Society of Reproductive Medicine. Reprod Med Biol. 2018 Oct. doi: 10.1002/rmb2.12236
Harada T, Ikuko O, Yusuke E, Hiroshi S, Hisashi N, Fuminori T. SR-16234, a Novel Selective Estrogen Receptor Modulator for Pain Symptoms with Endometriosis: An Open-label Clinical Trial. Yonago Acta Med. 2018 Feb. doi: 10.24563/yam.2017.12.003
Taniguchi F, Takashi U, Kazuomi N, Khine Yin Mon, Takashi H, Tetsuya O, Tasuku H. Inhibition of IAP (inhibitor of apoptosis) proteins represses inflammatory status via nuclear factor-kappa B pathway in murine endometriosis lesions. Am J Reprod Immunol. 2018 Jan. doi: 10.1111/aji.12780

2017年

Harada T, Takashi U, Kazuya A, Takako T, Fuminori T, Tasuku H. Schizencephaly and Porencephaly Due to Fetal Intracranial Hemorrhage: A Report of Two Cases. Yonago Acta Med. 2017 Dec. doi: 10.24563/yam.2017.12.005
Tasuku H. Saori K, Joerg E, Masanobu Y, Makoto I, Mikio M. Ethinylestradiol 20 μg/drospirenone 3 mg in a flexible extended regimen for the management of endometriosis-associated pelvic pain: a randomized controlled trial. Fertil Steril. 2017 Nov. doi: 10.1016/j.fertnstert.2017.07.1165
Taniguchi F, Akiko E, Ai I, Emiko Y, Maako M, Jiro M, Takashi H, Tasuku H. Efficacy of Norethisterone in Patients with Ovarian Endometrioma. Yonago Acta Med. 2017:60(3): 182-185
Taniguchi F. New knowledge and insights about the malignant transformation of endometriosis. J Obstet Gynaecol Res. 2017 Jul. doi: 10.1111/jog.13372
Azuma Y, Taniguchi F, Nakamura K, Nagira K, Khine YM, Kiyama T, Uegaki T, Izawa M, Harada T. Lipopolysaccharide promotes the development of murine endometriosis-like lesions via the nuclear factor-kappa B pathway. Am J Reprod Immunol. 2017 Jan 31. doi: 10.1111/aji.12631. [Epub ahead of print]

2016年

Harada T, Taniguchi F, Onishi K, Kurozawa Y, Hayashi K, Harada T; Japan Environment & Children's Study Group.. Obstetrical Complications in Women with Endometriosis: A Cohort Study in Japan. PLoS One. 2016 Dec 22;11(12):e0168476.
Taniguchi F, Sakamoto Y, Yabuta Y, Azuma Y, Hirakawa E, Nagira K, Uegaki T, Deura I, Hata K, Harada T. Analysis of pregnancy outcome and decline of anti-Müllerian hormone after laparoscopic cystectomy for ovarian endometriomas. J Obstet Gynaecol Res. 2016 Nov;42(11):1534-1540.
Harada T, Khine YM, Kaponis A, Nikellis T, Decavalas G, Taniguchi F. The Impact of Adenomyosis on Women's Fertility. Obstet Gynecol Surv. 2016 Sep;71(9):557-68.
Taniguchi F, Hirakawa E, Azuma Y, Uejima C, Ashida K, Harada T. Primary Umbilical Endometriosis: Unusual and Rare Clinical Presentation. Case Rep Obstet Gynecol. 2016;2016:9302376. doi: 10.1155/2016/9302376.

2015年

Izawa M, Taniguchi F, Harada T. Molecular Background of Estrogen Receptor Gene Expression in Endometriotic Cells. Reprod Sci. 2015 Dec 23.
Taniguchi F, Enatsu A, Ota I, Toda T, Arata K, Harada T. Effects of low dose oral contraceptive pill containing drospirenone/ethinylestradiol in patients with endometrioma. Eur J Obstet Gynecol Reprod Biol. 2015 Aug;191:116-20.
Kaponis A, Taniguchi F, Azuma Y, Deura I, Vitsas C, Decavalas GO, Harada T. Current treatment of endometrioma. Obstet Gynecol Surv. 2015 Mar;70(3):183-95.
Uegaki T, Taniguchi F, Nakamura K, Osaki M, Okada F, Yamamoto O, Harada T. Inhibitor of apoptosis proteins (IAPs) may be effective therapeutic targets for treating endometriosis. Hum Reprod. 2015 Jan;30(1):149-58.

2014年

Taniguchi F, Higaki H, Izawa M, Azuma Y, Hirakawa E, Deura I, Iwabe T, Hata K, Harada T. The cellular inhibitor of apoptosis protein-2 is a possible target of novel treatment for endometriosis. Am J Reprod Immunol. 2014; 71(3):278-85.
Taniguchi F, Harada T, Kobayashi H, Hayashi K, Momoeda M, Terakawa N. Clinical characteristics of patients in Japan with ovarian cancer presumably arising from ovarian endometrioma. Gynecol Obstet Invest. 2014; 77(2): 104-10.

2013年

Taniguchi F, Itamochi H, Harada T, Terakawa N. Fibroblast growth factor receptor 2 expression may be involved in transformation of ovarian endometrioma to clear cell carcinoma of the ovary. Int J Gynecol Cancer. 2013; 23 (5):791-6.
Takai E, Taniguchi F, Nakamura K, Uegaki T, Iwabe T, Harada T. Parthenolide reduces cell proliferation and prostaglandin E2 synthesis in human endometriotic stromal cells and inhibits development of endometriosis in the murine model. Fertil Steril. 2013; 100(4): 1170-8.
Taniguchi F, Higaki H, Azuma Y, Deura I, Iwabe T, Harada T, Terakawa N. Gonadotropin-releasing hormone analogues reduce the proliferation of endometrial stromal cells but not endometriotic cells. Gynecol Obstet Invest. 2013; 75(1): 9-15.
Izawa M, Taniguchi F, Terakawa N, Harada T. Epigenetic aberration of gene expression in endometriosis. Front Biosci (Elite Ed). 2013: 5: 900-10.

2012年

Kaponis A, Iwabe T, Taniguchi F, Ito M, Deura I, Decavalas G, Terakawa N, Harada T. The role of NF-kappaB in endometriosis. Front Biosci (Schol Ed). 2012;4:1213-34. Review.

2011年

Taniguchi F, Kaponis A, Izawa M, Kiyama T, Deura I, Ito M, Iwabe T, Adonakis G, Terakawa N, Harada T. Apoptosis and endometriosis. Front Biosci (Elite Ed). 2011: 1;3: 648-62. Review.
Suou K, Taniguchi F, Tagashira Y, Kiyama T, Terakawa N, Harada T. Apigenin inhibits tumor necrosis factor α-induced cell proliferation and prostaglandin E2 synthesis by inactivating NFκB in endometriotic stromal cells. Fertil Steril. 2011: 95(4): 1518-21.
Kaponis A, Harada T, Makrydimas G, Kiyama T, Arata K, Adonakis G, Tsapanos V, Iwabe T, Stefos T, Decavalas G, Harada T. The importance of venous Doppler velocimetry for evaluation of intrauterine growth restriction. J Ultrasound Med. 2011; 30(4): 529-45. Review.
Izawa M, Taniguchi F, Uegaki T, Takai E, Iwabe T, Terakawa N, Harada T. Demethylation of a nonpromoter cytosine-phosphate-guanine island in the aromatase gene may cause the aberrant up-regulation in endometriotic tissues. Fertil Steril. 2011; 95(1): 33-9.

2010年

Harada T, Taniguchi F.Dienogest: a new therapeutic agent for the treatment of endometriosis.Womens Health (Lond Engl). 2010; 6(1): 27-35. Review.
Takenaka Y, Taniguchi F, Miyakoda H, Takai E, Terakawa N, Harada T. Lipopolysaccharide promoted proliferation and invasion of endometriotic stromal cells via induction of cyclooxygenase-2 expression. Fertil Steril. 2010; 93(1): 325-7.

2009年

Taniguchi F, Harada T, Miyakoda H, Iwabe T, Deura I, Tagashira Y, Miyamoto A, Watanabe A, Suou K, Uegaki T, Terakawa N. TAK1 activation for cytokine synthesis and proliferation of endometriotic cells. Mol Cell Endocrinol. 2009, 13; 307(1-2): 196-204.
Watanabe A, Taniguchi F, Izawa M, Suou K, Uegaki T, Takai E, Terakawa N, Harada T. The role of survivin in the resistance of endometriotic stromal cells to drug-induced apoptosis. Hum Reprod. 2009 ; 24(12): 3172-9.
Miyamoto A, Taniguchi F, Tagashira Y, Watanabe A, Harada T, Terakawa N. TNFalpha gene silencing reduced lipopolysaccharide-promoted proliferation of endometriotic stromal cells. Am J Reprod Immunol. 2009; 61(4): 277-85.
Tagashira Y, Taniguchi F, Harada T, Ikeda A, Watanabe A, Terakawa N. Interleukin-10 attenuates TNF-alpha-induced interleukin-6 production in endometriotic stromal cells. Fertil Steril. 2009; 91(5 Suppl): 2185-92.

2008年

Ohata Y, Harada T, Miyakoda H, Taniguchi F, Iwabe T, Terakawa N. Serum interleukin-8 levels are elevated in patients with ovarian endometrioma. Fertil Steril. 2008; 90(4):994-9.
Izawa M, Harada T, Taniguchi F, Ohama Y, Takenaka Y, Terakawa N. An epigenetic disorder may cause aberrant expression of aromatase gene in endometriotic stromal cells. Fertil Steril. 2008; 89(5 Suppl): 1390-6.
Ohama Y, Harada T, Iwabe T, Taniguchi F, Takenaka Y, Terakawa N. Peroxisome proliferator-activated receptor-gamma ligand reduced tumor necrosis factor-alpha-induced interleukin-8 production and growth in endometriotic stromal cells. Fertil Steril. 2008; 89(2): 311-7.
Taniguchi F, Harada T, Iwabe T, Ohama Y, Takenaka Y, Terakawa N. Aberrant expression of keratinocyte growth factor receptor in ovarian surface epithelial cells of endometrioma. Fertil Steril. 2008; 89(2): 478-80.