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1. A 5-year multicentre randomized controlled trial comparing personalized, frozen and fresh blastocyst transfer in IVF

Author

Simon C, Gomez C, Cabanillas S, Vladimirov I, Castillon G, Giles J, Boynukalin K, Findikli N, Bahceci M, Ortega I, Vidal C, Funabiki M, Izquierdo A, Lopez L, Portela S, Frantz N, Kulmann M, Taguchi S, Labarta E, Colucci F, Mackens S, Santamaria X, Munoz E, Barrera S, Garcia-Velasco J, Fernandez M, Ferrando M, Ruiz M, Mol B, Valbuena D, and ERA-RCT Study Consortium Group

Subjects
embryonic structures
Abstract

RESEARCH QUESTION: Does clinical performance of personalized embryo transfer (PET) guided by endometrial receptivity analysis (ERA) differ from frozen embryo transfer (FET) or fresh embryo transfer in infertile patients undergoing IVF?; DESIGN: Multicentre, open-label randomized controlled trial; 458 patients aged 37 years or younger undergoing IVF with blastocyst transfer at first appointment were randomized to PET guided by ERA, FET or fresh embryo transfer in 16 reproductive clinics.; RESULTS: Clinical outcomes by intention-to-treat analysis were comparable, but cumulative pregnancy rate was significantly higher in the PET (93.6%) compared with FET (79.7%) (P?=?0.0005) and fresh embryo transfer groups (80.7%) (P?=?0.0013). Analysis per protocol demonstrates that live birth rates at first embryo transfer were 56.2% in PET versus 42.4% in FET (P?=?0.09), and 45.7% in fresh embryo transfer groups (P?=?0.17). Cumulative live birth rates after 12 months were 71.2% in PET versus 55.4% in FET (P?=?0.04), and 48.9% in fresh embryo transfer (P?=?0.003). Pregnancy rates at the first embryo transfer in PET, FET and fresh embryo transfer arms were 72.5% versus 54.3% (P?=?0.01) and 58.5% (P?=?0.05), respectively. Implantation rates at first embryo transfer were 57.3% versus 43.2% (P?=?0.03), and 38.6% (P?=?0.004), respectively. Obstetrical outcomes, type of delivery and neonatal outcomes were similar in all groups.; CONCLUSIONS: Despite 50% of patients dropping out compared with 30% initially planned, per protocol analysis demonstrates statistically significant improvement in pregnancy, implantation and cumulative live birth rates in PET compared with FET and fresh embryo transfer arms, indicating the potential utility of PET guided by the ERA test at the first appointment. Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

Published
2020

7. The implantation rate of japanese infertile patients with repeated implantation failure can be improved by endometrial receptivity array (era) test: a randomized controlled trial

Author

Taguchi, S., primary, Funabiki, M., additional, Hayashi, T., additional, Tada, Y., additional, Iwaki, Y., additional, Karita, M., additional, Ota, T., additional, Maeda, K., additional, Matsubara, T., additional, Zada, P., additional, Sugiyama, N., additional, and Nakamura, Y., additional

Published
2018
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9. Unusual inflammation in gynecologic pathology associated with defective endometrial receptivity

Author

Kitaya, K., Yasuo, T., Tada, Y., Hayashi, T., Iwaki, Y., Karita, M., Funabiki, M., Taguchi, S., Spillers, D., Nakamura, Y., and Hisao Yamada

Subjects
Endometrium, 5 - Ciencias puras y naturales::57 - Biología::576 - Biología celular y subcelular. Citología [CDU], Embryo implantation, Implantation failure, Immune responses
Abstract

Human cycling endometrium displays a series of periodic transitions unique to this mucosal tissue, which includes rapid proliferation, secretory transformation, physiological angiogenesis, interstitial edema, and menstrual shedding. Among these properties of the endometrium are the inflammatory changes that occur dynamically across the menstrual cycle. Immunocompetent cell composition and inflammatory gene expression pattern in the human endometrium drastically fluctuate from the proliferative phase to the secretory phase, particularly at the time of ovulation. These local immune responses are fine-tuned by the direct or indirect action of two representative ovarian steroids, estradiol and progesterone, and are essential for successful blastocyst implantation. Meanwhile, studies have been accumulating the evidence that such physiological endometrial inflammatory status is altered in the presence of certain gynecologic pathologies. Given that blastocysts are semi-allografts for maternal tissue, even subtle alterations in endometrial immunity potentially have a negative impact on implantation process. In this article, we aimed to review and discuss the physiological and pathological mucosal inflammatory conditions that can affect endometrial receptivity.

Published
2014

21. Reproductive endocrinology

Author

Nazzaro, A., primary, Salerno, A., additional, Di Iorio, L., additional, Landino, G., additional, Marino, S., additional, Pastore, E., additional, Fabregues, F., additional, Iraola, A., additional, Casals, G., additional, Creus, M., additional, Peralta, S., additional, Penarrubia, J., additional, Manau, D., additional, Civico, S., additional, Balasch, J., additional, Lindgren, I., additional, Giwercman, Y. L., additional, Celik, E., additional, Turkcuoglu, I., additional, Ata, B., additional, Karaer, A., additional, Kirici, P., additional, Berker, B., additional, Park, J., additional, Kim, J., additional, Rhee, J., additional, Krishnan, M., additional, Rustamov, O., additional, Russel, R., additional, Fitzgerald, C., additional, Roberts, S., additional, Hapuarachi, S., additional, Tan, B. K., additional, Mathur, R. S., additional, van de Vijver, A., additional, Blockeel, C., additional, Camus, M., additional, Polyzos, N., additional, Van Landuyt, L., additional, Tournaye, H., additional, Turhan, N. O., additional, Hizli, D., additional, Kamalak, Z., additional, Kosus, A., additional, Kosus, N., additional, Kafali, H., additional, Lukaszuk, A., additional, Kunicki, M., additional, Liss, J., additional, Bednarowska, A., additional, Jakiel, G., additional, Lukaszuk, K., additional, Lukaszuk, M., additional, Olszak-Sokolowska, B., additional, Wasniewski, T., additional, Neuberg, M., additional, Cavalcanti, V., additional, Peluso, C., additional, Lechado, B. L., additional, Cordts, E. B., additional, Christofolini, D. M., additional, Barbosa, C. P., additional, Bianco, B., additional, Venetis, C. A., additional, Kolibianakis, E. M., additional, Bosdou, J., additional, Tarlatzis, B. C., additional, Onal, M., additional, Gungor, D. N., additional, Acet, M., additional, Kahraman, S., additional, Kuijper, E., additional, Twisk, J., additional, Caanen, M., additional, Korsen, T., additional, Hompes, P., additional, Kushnir, M., additional, Rockwood, A., additional, Meikle, W., additional, Lambalk, C. B., additional, Yan, X., additional, Dai, X., additional, Wang, J., additional, Zhao, N., additional, Cui, Y., additional, Liu, J., additional, Yarde, F., additional, Maas, A. H. E. M., additional, Franx, A., additional, Eijkemans, M. J. C., additional, Drost, J. T., additional, van Rijn, B. B., additional, van Eyck, J., additional, van der Schouw, Y. T., additional, Broekmans, F. J. M., additional, Martyn, F., additional, Anglim, B., additional, Wingfield, M., additional, Fang, T., additional, Yan, G. J., additional, Sun, H. X., additional, Hu, Y. L., additional, Chrudimska, J., additional, Krenkova, P., additional, Macek, M., additional, Teixeira da Silva, J., additional, Cunha, M., additional, Silva, J., additional, Viana, P., additional, Goncalves, A., additional, Barros, N., additional, Oliveira, C., additional, Sousa, M., additional, Barros, A., additional, Nelson, S. M., additional, Lloyd, S. M., additional, McConnachie, A., additional, Khader, A., additional, Fleming, R., additional, Lawlor, D. A., additional, Thuesen, L., additional, Andersen, A. N., additional, Loft, A., additional, Smitz, J., additional, Abdel-Rahman, M., additional, Ismail, S., additional, Silk, J., additional, Abdellah, M., additional, Abdellah, A. H., additional, Ruiz, F., additional, Cruz, M., additional, Piro, M., additional, Collado, D., additional, Garcia-Velasco, J. A., additional, Requena, A., additional, Kollmann, Z., additional, Bersinger, N. A., additional, McKinnon, B., additional, Schneider, S., additional, Mueller, M. D., additional, von Wolff, M., additional, Vaucher, A., additional, Weiss, B., additional, Stute, P., additional, Marti, U., additional, Chai, J., additional, Yeung, W. Y. T., additional, Lee, C. Y. V., additional, Li, W. H. R., additional, Ho, P. C., additional, Ng, H. Y. E., additional, Kim, S. M., additional, Kim, S. H., additional, Jee, B. C., additional, Ku, S., additional, Suh, C. S., additional, Choi, Y. M., additional, Kim, J. G., additional, Moon, S. Y., additional, Lee, J. H., additional, Kim, S. G., additional, Kim, Y. Y., additional, Kim, H. J., additional, Lee, K. H., additional, Park, I. H., additional, Sun, H. G., additional, Hwang, Y. I., additional, Sung, N. Y., additional, Choi, M. H., additional, Cha, S. H., additional, Park, C. W., additional, Kim, J. Y., additional, Yang, K. M., additional, Song, I. O., additional, Koong, M. K., additional, Kang, I. S., additional, Kim, H. O., additional, Haines, C., additional, Wong, W. Y., additional, Kong, W. S., additional, Cheung, L. P., additional, Choy, T. K., additional, Leung, P. C., additional, Fadini, R., additional, Coticchio, G., additional, Renzini, M. M., additional, Guglielmo, M. C., additional, Brambillasca, F., additional, Hourvitz, A., additional, Albertini, D. F., additional, Novara, P., additional, Merola, M., additional, Dal Canto, M., additional, Iza, J. A. A., additional, DePablo, J. L., additional, Anarte, C., additional, Domingo, A., additional, Abanto, E., additional, Barrenetxea, G., additional, Kato, R., additional, Kawachiya, S., additional, Bodri, D., additional, Kondo, M., additional, Matsumoto, T., additional, Maldonado, L. G. L., additional, Setti, A. S., additional, Braga, D. P. A. F., additional, Iaconelli, A., additional, Borges, E., additional, Iaconelli, C., additional, Figueira, R. C. S., additional, Kitaya, K., additional, Taguchi, S., additional, Funabiki, M., additional, Tada, Y., additional, Hayashi, T., additional, Nakamura, Y., additional, Snajderova, M., additional, Zemkova, D., additional, Lanska, V., additional, Teslik, L., additional, Calonge, R. N. -, additional, Ortega, L., additional, Garcia, A., additional, Cortes, S., additional, Guijarro, A., additional, Peregrin, P. C., additional, Bellavia, M., additional, Pesant, M. H., additional, Wirthner, D., additional, Portman, L., additional, de Ziegler, D., additional, Wunder, D., additional, Chen, X., additional, Chen, S. H. L., additional, Liu, Y. D., additional, Tao, T., additional, Xu, L. J., additional, Tian, X. L., additional, Ye, D. S. H., additional, He, Y. X., additional, Carby, A., additional, Barsoum, E., additional, El-Shawarby, S., additional, Trew, G., additional, Lavery, S., additional, Mishieva, N., additional, Barkalina, N., additional, Korneeva, I., additional, Ivanets, T., additional, Abubakirov, A., additional, Chavoshinejad, R., additional, Hartshorne, G. m., additional, Marei, W., additional, Fouladi-nashta, A. a., additional, Kyrkou, G., additional, Trakakis, E., additional, Chrelias, C. H., additional, Alexiou, E., additional, Lykeridou, K., additional, Mastorakos, G., additional, Bersinger, N., additional, Ferrero, H., additional, Gomez, R., additional, Garcia-Pascual, C. M., additional, Simon, C., additional, Pellicer, A., additional, Turienzo, A., additional, Lledo, B., additional, Guerrero, J., additional, Ortiz, J. A., additional, Morales, R., additional, Ten, J., additional, Llacer, J., additional, Bernabeu, R., additional, De Leo, V., additional, Focarelli, R., additional, Capaldo, A., additional, Stendardi, A., additional, Gambera, L., additional, Marca, A. L., additional, Piomboni, P., additional, Kim, J. J., additional, Kang, J. H., additional, Hwang, K. R., additional, Chae, S. J., additional, Yoon, S. H., additional, Ku, S. Y., additional, Iliodromiti, S., additional, Kelsey, T. W., additional, Anderson, R. A., additional, Lee, H. J., additional, Weghofer, A., additional, Kushnir, V. A., additional, Shohat-Tal, A., additional, Lazzaroni, E., additional, Barad, D. H., additional, Gleicher, N. N., additional, Shavit, T., additional, Shalom-Paz, E., additional, Fainaru, O., additional, Michaeli, M., additional, Kartchovsky, E., additional, Ellenbogen, A., additional, Gerris, J., additional, Vandekerckhove, F., additional, Delvigne, A., additional, Dhont, N., additional, Madoc, B., additional, Neyskens, J., additional, Buyle, M., additional, Vansteenkiste, E., additional, De Schepper, E., additional, Pil, L., additional, Van Keirsbilck, N., additional, Verpoest, W., additional, Debacquer, D., additional, Annemans, L., additional, De Sutter, P., additional, Von Wolff, M., additional, Bersinger, N. a., additional, Verit, F. F., additional, Keskin, S., additional, Sargin, A. K., additional, Karahuseyinoglu, S., additional, Yucel, O., additional, Yalcinkaya, S., additional, Comninos, A. N., additional, Jayasena, C. N., additional, Nijher, G. M. K., additional, Abbara, A., additional, De Silva, A., additional, Veldhuis, J. D., additional, Ratnasabapathy, R., additional, Izzi-Engbeaya, C., additional, Lim, A., additional, Patel, D. A., additional, Ghatei, M. A., additional, Bloom, S. R., additional, Dhillo, W. S., additional, Colodron, M., additional, Guillen, J. J., additional, Garcia, D., additional, Coll, O., additional, Vassena, R., additional, Vernaeve, V., additional, Pazoki, H., additional, Bolouri, G., additional, Farokhi, F., additional, Azarbayjani, M. A., additional, Alebic, M. S., additional, Stojanovic, N., additional, Abali, R., additional, Yuksel, A., additional, Aktas, C., additional, Celik, C., additional, Guzel, S., additional, Erfan, G., additional, Sahin, O., additional, Zhongying, H., additional, Shangwei, L., additional, Qianhong, M., additional, Wei, F., additional, Lei, L., additional, Zhun, X., additional, Yan, W., additional, De Baerdemaeker, A., additional, Tilleman, K., additional, Vansteelandt, S., additional, Oliveira, J. B. A., additional, Baruffi, R. L. R., additional, Petersen, C. G., additional, Mauri, A. L., additional, Nascimento, A. M., additional, Vagnini, L., additional, Ricci, J., additional, Cavagna, M., additional, Massaro, F. C., additional, Pontes, A., additional, Franco, J. G., additional, El-khayat, W., additional, Elsadek, M., additional, Foroozanfard, F., additional, Saberi, H., additional, Moravvegi, A., additional, Kazemi, M., additional, Gidoni, Y. S., additional, Raziel, A., additional, Friedler, S., additional, Strassburger, D., additional, Hadari, D., additional, Kasterstein, E., additional, Ben-Ami, I., additional, Komarovsky, D., additional, Maslansky, B., additional, Bern, O., additional, Ron-El, R., additional, Izquierdo, M. P., additional, Araico, F., additional, Somova, O., additional, Feskov, O., additional, Feskova, I., additional, Bezpechnaya, I., additional, Zhylkova, I., additional, Tishchenko, O., additional, Oguic, S. K., additional, Baldani, D. P., additional, Skrgatic, L., additional, Simunic, V., additional, Vrcic, H., additional, Rogic, D., additional, Juras, J., additional, Goldstein, M. S., additional, Garcia De Miguel, L., additional, Campo, M. C., additional, Gurria, A., additional, Alonso, J., additional, Serrano, A., additional, Marban, E., additional, Shalev, L., additional, Yung, Y., additional, Yerushalmi, G., additional, Giovanni, C., additional, Has, J., additional, Maman, E., additional, Monterde, M., additional, Marzal, A., additional, Vega, O., additional, Rubio, J. m., additional, Diaz-Garcia, C., additional, Eapen, A., additional, Datta, A., additional, Kurinchi-selvan, A., additional, Birch, H., additional, Lockwood, G. M., additional, Ornek, M. C., additional, Ates, U., additional, Usta, T., additional, Goksedef, C. P., additional, Bruszczynska, A., additional, Glowacka, J., additional, Jaguszewska, K., additional, Oehninger, S., additional, Nelson, S., additional, Verweij, P., additional, Stegmann, B., additional, Ando, H., additional, Takayanagi, T., additional, Minamoto, H., additional, Suzuki, N., additional, Rubinshtein, N., additional, Saltek, S., additional, Demir, B., additional, Dilbaz, B., additional, Demirtas, C., additional, Kutteh, W., additional, Shapiro, B., additional, Witjes, H., additional, Gordon, K., additional, Lauritsen, M. P., additional, Pinborg, A., additional, Freiesleben, N. L., additional, Mikkelsen, A. L., additional, Bjerge, M. R., additional, Chakraborty, P., additional, Goswami, S. K., additional, Chakravarty, B. N., additional, Mittal, M., additional, Bajoria, R., additional, Narvekar, N., additional, Chatterjee, R., additional, Bentzen, J. G., additional, Johannsen, T. H., additional, Scheike, T., additional, Friis-Hansen, L., additional, Sunkara, S., additional, Coomarasamy, A., additional, Faris, R., additional, Braude, P., additional, Khalaf, Y., additional, Makedos, A., additional, Masouridou, S., additional, Chatzimeletiou, K., additional, Zepiridis, L., additional, Mitsoli, A., additional, Lainas, G., additional, Sfontouris, I., additional, Tzamtzoglou, A., additional, Kyrou, D., additional, Lainas, T., additional, Fermin, A., additional, Crisol, L., additional, Exposito, A., additional, Prieto, B., additional, Mendoza, R., additional, Matorras, R., additional, Louwers, Y., additional, Lao, O., additional, Kayser, M., additional, Palumbo, A., additional, Sanabria, V., additional, Rouleau, J. P., additional, Puopolo, M., additional, Hernandez, M. J., additional, Rubio, J. M., additional, Ozturk, S., additional, Sozen, B., additional, Yaba-Ucar, A., additional, Mutlu, D., additional, Demir, N., additional, Olsson, H., additional, Sandstrom, R., additional, Grundemar, L., additional, Papaleo, E., additional, Corti, L., additional, Rabellotti, E., additional, Vanni, V. S., additional, Potenza, M., additional, Molgora, M., additional, Vigano, P., additional, Candiani, M., additional, Fernandez-Sanchez, M., additional, Bosch, E., additional, Visnova, H., additional, Barri, P., additional, Fauser, B. J. C. M., additional, Arce, J. C., additional, Peluso, P., additional, Trevisan, C. M., additional, Fonseca, F. A., additional, Bakas, P., additional, Vlahos, N., additional, Hassiakos, D., additional, Tzanakaki, D., additional, Gregoriou, O., additional, Liapis, A., additional, Creatsas, G., additional, Adda-Herzog, E., additional, Steffann, J., additional, Sebag-Peyrelevade, S., additional, Poulain, M., additional, Benachi, A., additional, Fanchin, R., additional, Zhang, D., additional, Aybar, F., additional, Temel, S., additional, Hamdine, O., additional, Macklon, N. S., additional, Laven, J. S., additional, Cohlen, B. J., additional, Verhoeff, A., additional, van Dop, P. A., additional, Bernardus, R. E., additional, Oosterhuis, G. J. E., additional, Holleboom, C. A. G., additional, van den Dool-Maasland, G. C., additional, Verburg, H. J., additional, van der Heijden, P. F. M., additional, Blankhart, A., additional, Fauser, B. C. J. M., additional, Broekmans, F. J., additional, Bhattacharya, J., additional, Mitra, A., additional, Dutta, G. B., additional, Kundu, A., additional, Bhattacharya, M., additional, Kundu, S., additional, Pigny, P., additional, Dassonneville, A., additional, Catteau-Jonard, S., additional, Decanter, C., additional, Dewailly, D., additional, Pouly, J., additional, Olivennes, F., additional, Massin, N., additional, Celle, M., additional, Caizergues, N., additional, Gaudoin, M., additional, Messow, M., additional, Vanhove, L., additional, Peigne, M., additional, Thomas, P., additional, and Robin, G., additional

Published
2013
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31. Genetic Counseling for an Infertile Couple With Premature Chromatid Separation (PCS) Syndrome: A Case Report.

Author

Taguchi S, Hayashi T, Watanabe N, Tada Y, Matsubara T, Calongos G, Yamamoto K, Fujishima R, Imoto S, Funabiki M, and Nakamura Y

Abstract

We report the first case of successful genetic counseling for an infertile couple with premature chromatid separation (PCS) syndrome. After our careful genetic counseling, the couple decided to continue infertility treatment. As a result, they gave birth to a baby (girl: 2,930 g) by caesarean section in May 2018. To our knowledge, there have not been any published reports regarding genetic counseling for an infertile couple with PCS after PubMed, EMBASE, and Web of Science searches until March 2024., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Taguchi et al.)

Published
2024
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32. Endometrial Receptivity Array (ERA) Test in a 32-Year-Old Female With Refractory Infertility: A Case Report.

Author

Imoto S, Funabiki M, Nakamura Y, and Taguchi S

Abstract

We report a successful case for the clinical efficacy of the endometrial receptivity array (ERA) test for a 32-year-old female patient with refractory infertility. After our careful treatment, the patient gave birth to a male baby (3390 g) in November 2021. To our knowledge, though the clinical efficacy of the ERA test is controversial until March 2024, we think that the age of the patients, the number of IVF cycles, and the racial differences may have an impact on the clinical efficacy of the ERA test., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Imoto et al.)

Published
2024
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33. SAPHO Syndrome Complicated by Lesions of the Central Nervous System Successfully Treated with Brodalumab.

Author

Funabiki M, Tahara M, Kondo S, Ayuzawa N, and Yanagida H

Abstract

Synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome is a rare disease with an unknown entity that affects the skin and the peripheral and/or axial joints. Here, we report on a patient with SAPHO syndrome complicated by lesions of the central nervous system who was successfully treated with brodalumab, an IL-17 receptor blocker. He had been suffering from arthralgia in the wrists and knees as well as axial symptoms such as back pain and assimilation of cervical vertebrae. He had been treated with corticosteroid, salazosulfapyridine, methotrexate, and bisphosphonate; however, his peripheral and axial articular manifestation were intractable. Recently, biologics predominantly targeting TNF- α is employed for difficult-to-treat SAPHO cases; however, he had been complicated with the lesions of the central nervous system resembling multiple sclerosis (MS), an inflammatory demyelinating disorder in the central nervous system, for which application of TNF- α inhibitor is contraindicated. Alternatively, brodalumab was administered , which promptly ameliorated the articular manifestations without aggravating the lesions of the central nervous system. We propose that this type of IL-17 blockade could be an alternative therapy for DMARDs-resistant SAPHO syndrome., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Masahide Funabiki et al.)

Published
2023
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34. Older Women's Reproductive Outcomes May Not Be Improved by the Endometrial Receptivity Analysis Test: A Case Report.

Author

Fujishima R, Funabiki M, Nakamura Y, and Taguchi S

Abstract

We report a case of a 39-year-old woman with refractory recurrent implantation failure by using endometrial receptivity analysis (ERA) test. According to a recent randomized controlled trial (RCT) study, the ERA test is expected as a helpful tool for the treatment ofinfertile patients with recurrent implantation failures. However, even in the recent RCT study, the efficacy for the ERA test for older patients (more than 38 years old) is still unclear, as the inclusion criterion for the patients in the RCT study was age 37 years or younger. In our research, the patient was 39 years old at the time of the first visit to our clinic. Therefore, the clinical utility of the ERA test may depend on the patient's age. In order to confirm the hypothesis, RCT study for older patients (more than 38 years old) should be conducted. In conclusion, our research showed the limitation of ERA test in patients with recurrent implantation failures. This will save not only our resources but also time before implying any test or investigation for the diagnosis as well management in such patients. Our research will be a good step in the management of such patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Fujishima et al.)

Published
2021
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35. Characterization and proposed spontaneous deletion mechanism of AVR-Pik locus in Pyricularia oryzae.

Author

Thwin PH, Funabiki M, Tomita Y, Yamazaki T, Abe A, and Sone T

Subjects
DNA Transposable Elements genetics, Fungal Proteins genetics, Fungal Proteins metabolism, Genetic Loci, Base Sequence, Sequence Deletion, Gene Deletion, Homologous Recombination, Plant Diseases microbiology, Plant Diseases genetics, Mutation, Ascomycota genetics
Abstract

In phytopathogenic fungi, a mutation in the avirulence gene can lead to the breakdown of resistance in the host plant. The nucleotide sequences of the AVR-Pik locus in the strain Ina168 and its spontaneous mutant Ina168m95-5 of Pyricularia oryzae were determined. An AVR-Pik spontaneous deletion mechanism of Ina168m95-5, including multiple homologous recombination events involving repetitive transposable elements, is proposed., (© The Author(s) 2021. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Published
2021
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36. Aicardi-Goutières syndrome-like encephalitis in mutant mice with constitutively active MDA5.

Author

Onizawa H, Kato H, Kimura H, Kudo T, Soda N, Shimizu S, Funabiki M, Yagi Y, Nakamoto Y, Priller J, Nishikomori R, Heike T, Yan N, Tsujimura T, Mimori T, and Fujita T

Subjects
Animals, Autoantibodies blood, Disease Models, Animal, Encephalitis pathology, Interferon-Induced Helicase, IFIH1 genetics, Lymphocytes immunology, Mice, Mice, Knockout, Microglia metabolism, Autoimmune Diseases of the Nervous System genetics, Autoimmune Diseases of the Nervous System pathology, Encephalitis genetics, Interferon Type I immunology, Interferon-Induced Helicase, IFIH1 metabolism, Nervous System Malformations genetics, Nervous System Malformations pathology
Abstract

MDA5 is a cytoplasmic sensor of viral RNA, triggering type I interferon (IFN-I) production. Constitutively active MDA5 has been linked to autoimmune diseases such as systemic lupus erythematosus, Singleton-Merten syndrome (SMS) and Aicardi-Goutières syndrome (AGS), a genetically determined inflammatory encephalopathy. However, AGS research is challenging due to the lack of animal models. We previously reported lupus-like nephritis and SMS-like bone abnormalities in adult mice with constitutively active MDA5 (Ifih1G821S/+), and herein demonstrate that these mice also exhibit high lethality and spontaneous encephalitis with high IFN-I production during the early postnatal period. Increases in the number of microglia were observed in MDA5/MAVS signaling- and IFN-I-dependent manners. Furthermore, microglia showed an activated state with an increased phagocytic capability and reduced expression of neurotrophic factors. Although multiple auto-antibodies including lupus-related ones were detected in the sera of the mice as well as AGS patients, Ifih1G821S/+Rag2-/- mice also exhibited up-regulation of IFN-I, astrogliosis and microgliosis, indicating that auto-antibodies or lymphocytes are not required for the development of the encephalitis. The IFN-I signature without lymphocytic infiltration observed in Ifih1G821S/+ mice is a typical feature of AGS. Collectively, our results suggest that the Ifih1G821S/+ mice are a model recapitulating AGS and that microglia are a potential target for AGS therapy., (© The Japanese Society for Immunology. 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Published
2021
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37. Psoriasis-like skin disorder in transgenic mice expressing a RIG-I Singleton-Merten syndrome variant.

Author

Abu Tayeh A, Funabiki M, Shimizu S, Satoh S, Sumin L, Iwakura Y, Kato H, and Fujita T

Subjects
Animals, Aortic Diseases genetics, DNA-Binding Proteins genetics, Dendritic Cells immunology, Dental Enamel Hypoplasia genetics, Epidermis pathology, Hyperplasia genetics, Hyperplasia pathology, Janus Kinase Inhibitors pharmacology, Janus Kinases antagonists & inhibitors, Keratinocytes cytology, Keratinocytes pathology, Metacarpus abnormalities, Mice, Mice, Inbred C57BL, Mice, Knockout, Muscular Diseases genetics, Neutrophils immunology, Odontodysplasia genetics, Osteoporosis genetics, Piperidines pharmacology, Psoriasis genetics, Pyrimidines pharmacology, T-Lymphocytes immunology, Vascular Calcification genetics, DEAD Box Protein 58 genetics, DEAD Box Protein 58 metabolism, Interferon Type I immunology, Interleukin-17 metabolism, Interleukin-23 Subunit p19 metabolism, Psoriasis pathology
Abstract

Mutations in DDX58 (DExD/H-box helicase 58), which encodes the cytoplasmic RNA sensor retinoic acid-inducible gene I (RIG-I), were recently identified in the rare autoimmune disease Singleton-Merten syndrome (SMS). We report the spontaneous development of psoriasis-like skin lesions as an SMS-like symptom in transgenic mice harboring one of the RIG-I SMS variants, E373A. Histological analysis revealed typical characteristics of psoriasis, including the abnormal proliferation and differentiation of keratinocytes leading to epidermal hyperplasia, and infiltrates consisting of neutrophils, dendritic cells and T cells. Levels of the IL-23/IL-17 immune axis cytokines were high in the skin lesions. Rag2-/- transgenic mice showed partial amelioration of the phenotype, with down-regulation of inflammatory cytokines, including IL-17A, suggesting the importance of lymphocytes for the pathogenesis similar to that of human psoriasis. Of note, IL-17A deficiency abolished the skin phenotype, and treatment using the JAK inhibitor tofacitinib not only prevented onset, but also improved the skin manifestations even after onset. Our study provides further evidence for the involvement of RIG-I activation in the onset and progression of psoriasis via type I interferon signaling and the IL-23/IL-17 axis., (© The Japanese Society for Immunology. 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Published
2021
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39. Comprehensive endometrial immunoglobulin subclass analysis in infertile women suffering from repeated implantation failure with or without chronic endometritis.

Author

Kitaya K, Tada Y, Hayashi T, Taguchi S, Funabiki M, and Nakamura Y

Subjects
Embryo Implantation, Endometrium pathology, Female, Humans, Immunoglobulin A classification, Immunoglobulin A immunology, Immunoglobulin G classification, Immunoglobulin G immunology, Immunoglobulin M classification, Immunoglobulin M immunology, Infertility, Female, Inflammation immunology, Plasma Cells immunology, Endometritis immunology, Endometrium immunology, Immunoglobulin A biosynthesis, Immunoglobulin G biosynthesis, Immunoglobulin M biosynthesis
Abstract

Problem: Chronic endometritis (CE) is a local inflammatory condition with unusual plasmacyte infiltration in the endometrial stromal area. CE is frequently found in infertile women with repeated implantation failure (RIF). In this study, we comprehensively investigated the endometrial immunoglobulin (Ig) subclass expression in infertile women suffering from RIF with versus without CE., Method of Study: Endometrial biopsy specimens obtained from 28 infertile women with RIF and CE (the RIF-CE group), 23 infertile women with RIF but without CE (the RIF-non-CE group), and 22 proven fertile women undergoing hysterectomy for benign endometrial pathology (the control group) were immunostained for Ig subclass expression., Results: The density of IgM+, IgA1+, IgA2+, IgG1+, and IgG2+ stromal cells were significantly higher in the RIF-CE group than that in the RIF-non-CE and control group. The density of IgG2+ stromal cells was significantly higher than that of any other Ig subclass-positive cells (P<0.045) in the RIF-CE group. In serial section staining, the immunoreactivity for CD138 and Ig subclasses in the endometrial stroma was detectable in adjacent cells of some specimens in the RIF-CE group., Conclusions: The endometrium of infertile women with RIF-CE was characterized by increase in IgM, IgA, and IgG expression and predominance of IgG2 over other Ig subclasses., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Published
2014
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40. Unusual inflammation in gynecologic pathology associated with defective endometrial receptivity.

Author

Kitaya K, Yasuo T, Tada Y, Hayashi T, Iwaki Y, Karita M, Funabiki M, Taguchi S, Spillers D, Nakamura Y, and Yamada H

Subjects
Female, Humans, Embryo Implantation physiology, Endometrium pathology, Genital Diseases, Female pathology, Inflammation pathology
Abstract

Human cycling endometrium displays a series of periodic transitions unique to this mucosal tissue, which includes rapid proliferation, secretory transformation, physiological angiogenesis, interstitial edema, and menstrual shedding. Among these properties of the endometrium are the inflammatory changes that occur dynamically across the menstrual cycle. Immunocompetent cell composition and inflammatory gene expression pattern in the human endometrium drastically fluctuate from the proliferative phase to the secretory phase, particularly at the time of ovulation. These local immune responses are fine-tuned by the direct or indirect action of two representative ovarian steroids, estradiol and progesterone, and are essential for successful blastocyst implantation. Meanwhile, studies have been accumulating the evidence that such physiological endometrial inflammatory status is altered in the presence of certain gynecologic pathologies. Given that blastocysts are semi-allografts for maternal tissue, even subtle alterations in endometrial immunity potentially have a negative impact on implantation process. In this article, we aimed to review and discuss the physiological and pathological mucosal inflammatory conditions that can affect endometrial receptivity.

Published
2014
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41. Aicardi-Goutières syndrome is caused by IFIH1 mutations.

Author

Oda H, Nakagawa K, Abe J, Awaya T, Funabiki M, Hijikata A, Nishikomori R, Funatsuka M, Ohshima Y, Sugawara Y, Yasumi T, Kato H, Shirai T, Ohara O, Fujita T, and Heike T

Subjects
Amino Acid Sequence, Animals, DEAD-box RNA Helicases chemistry, Female, Humans, Interferon-Induced Helicase, IFIH1, Japan, Male, Molecular Sequence Data, Pedigree, Sequence Homology, Amino Acid, Autoimmune Diseases of the Nervous System genetics, DEAD-box RNA Helicases genetics, Mutation, Missense, Nervous System Malformations genetics
Abstract

Aicardi-Goutières syndrome (AGS) is a rare, genetically determined early-onset progressive encephalopathy. To date, mutations in six genes have been identified as etiologic for AGS. Our Japanese nationwide AGS survey identified six AGS-affected individuals without a molecular diagnosis; we performed whole-exome sequencing on three of these individuals. After removal of the common polymorphisms found in SNP databases, we were able to identify IFIH1 heterozygous missense mutations in all three. In vitro functional analysis revealed that IFIH1 mutations increased type I interferon production, and the transcription of interferon-stimulated genes were elevated. IFIH1 encodes MDA5, and mutant MDA5 lacked ligand-specific responsiveness, similarly to the dominant Ifih1 mutation responsible for the SLE mouse model that results in type I interferon overproduction. This study suggests that the IFIH1 mutations are responsible for the AGS phenotype due to an excessive production of type I interferon., (Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Published
2014
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42. Low follicular fluid tyrosine concentration in infertile women with ovarian hyperstimulation syndrome.

Author

Amano N, Kitaya K, Taguchi S, Funabiki M, Tada Y, Hayashi T, and Nakamura Y

Abstract

The aim of this study was to compare the branched-chain amino acid (BCAA) and tyrosine concentration in the follicular fluid of infertile women with and without ovarian hyperstimulation syndrome (OHSS) in an in vitro fertilization program combined with controlled ovarian stimulation. Follicular fluid was aspirated during oocyte retrieval from 20 infertile patients who developed moderate-to-severe OHSS and 20 age- and body mass index-matched normoresponders. BCAA and tyrosine concentration were measured using enzymatic methods. The follicular fluid BCAA concentration was similar between the two groups (P=0.55), whereas tyrosine concentration was significantly lower in the OHSS compared to that in the normoresponder group (P=0.027) and the BCAA/tyrosine ratio was significantly higher in the OHSS compared to that in the normoresponder group (P=0.034). These results suggest an association between low follicular fluid tyrosine concentration and OHSS. Dopamine receptor agonists may be used as potential anti-OHSS medicines and tyrosine, as a dopamine precursor, may play a role against the development of OHSS.

Published
2014
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43. Autoimmune disorders associated with gain of function of the intracellular sensor MDA5.

Author

Funabiki M, Kato H, Miyachi Y, Toki H, Motegi H, Inoue M, Minowa O, Yoshida A, Deguchi K, Sato H, Ito S, Shiroishi T, Takeyasu K, Noda T, and Fujita T

Subjects
Animals, Cells, Cultured, Disease Models, Animal, Interferon-Induced Helicase, IFIH1, Interferon-alpha genetics, Interferon-alpha metabolism, Mice, Mutation, Autoimmune Diseases genetics, Autoimmune Diseases physiopathology, DEAD-box RNA Helicases genetics, DEAD-box RNA Helicases metabolism
Abstract

MDA5 is an essential intracellular sensor for several viruses, including picornaviruses, and elicits antiviral interferon (IFN) responses by recognizing viral dsRNAs. MDA5 has been implicated in autoimmunity. However, the mechanisms of how MDA5 contributes to autoimmunity remain unclear. Here we provide direct evidence that dysregulation of MDA5 caused autoimmune disorders. We established a mutant mouse line bearing MDA5 mutation by ENU mutagenesis, which spontaneously developed lupus-like autoimmune symptoms without viral infection. Inflammation was dependent on an adaptor molecule, MAVS indicating the importance of MDA5-signaling. In addition, intercrossing the mutant mice with type I IFN receptor-deficient mice ameliorated clinical manifestations. This MDA5 mutant could activate signaling in the absence of its ligand but was paradoxically defective for ligand- and virus-induced signaling, suggesting that the mutation induces a conformational change in MDA5. These findings provide insight into the association between disorders of the innate immune system and autoimmunity., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Published
2014
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44. Neonatal dural arteriovenous fistula at the confluence presenting with paralysis of the orbicularis oris muscle.

Author

Iizuka Y, Koda E, Tsutsumi Y, Konishi Y, Ashida H, Nakanishi T, and Funabiki M

Subjects
Adult, Cerebral Angiography, Female, Functional Laterality, Humans, Infant, Newborn, Male, Pregnancy, Central Nervous System Vascular Malformations complications, Muscles physiopathology, Paralysis etiology, Paralysis pathology
Abstract

A male neonate presented a dural arteriovenous fistula (DAVF) at the confluence with paralysis of the orbicularis oris muscle. The interesting features in our case were the clinical symptoms (orbicularis oris muscle paralysis at birth), angioarchitecture (high-flow arteriovenous shunts at the confluence) and the size and hemodynamic flow (mid-sized venous pouch) of the fistula. Additionally, the embolization technique (i.e., occipital artery approach, closing shunts with pure glue) automatically resulted in the immediate and complete closure of accessory feeders without any additional treatment, and the midterm clinical outcome was good. We succeeded improving the symptoms of a neonate with a congenital high-flow DAVF by closing a fistula using a small amount of glue.

Published
2013
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45. Single curettage endometrial biopsy injury in the proliferative phase improves reproductive outcome of subsequent in vitro fertilization-embryo transfer cycle in infertile patients with repeated embryo implantation failure.

Author

Hayashi T, Kitaya K, Tada Y, Taguchi S, Funabiki M, and Nakamura Y

Subjects
Adult, Biopsy, Needle, Embryo Implantation, Embryo Implantation, Delayed, Embryo Loss prevention & control, Female, Fertilization in Vitro, Follicular Phase, Humans, Pregnancy, Embryo Transfer, Endometrium pathology, Infertility, Female therapy, Pregnancy Outcome
Abstract

Purpose of Investigation: To evaluate the effectiveness of single curettage endometrial biopsy injury (EBI) in the proliferative phase for in vitro fertilization-embryo transfer (IVF-ET) outcome of the subsequent cycle in infertile patients with repeated embryo implantation failure (EIF)., Materials and Methods: Of 89 patients who repeated EIF three times following transfer of morphologically good embryos and/or blastocysts, 40 patients chose curettage EBI prior to the subsequent IVF-ET cycle. Using a three-mm wide curette, EBI was performed once between days 6 and 12 of the spontaneous cycle. Their IVF-ET outcomes in the subsequent cycle were compared with those in 49 patients who did not opt for EBI., Results: The clinical pregnancy rate (37.5% vs 12.2%), embryo implantation rate (23.6% vs 6.3%), and ongoing pregnancy rate (25.0% vs 8.2%) were significantly higher in the EBI group than in the non-EBI group. No serious complaints and complications were noted., Conclusion: Single curettage EBI in the proliferative phase of the preceding cycle significantly improved IVF-ET outcome in infertile patients with repeated EIF.

Published
2013

46. Diverse functions of uterine proteoglycans in human reproduction (review).

Author

Kitaya K, Tada Y, Hayashi T, Taguchi S, Funabiki M, Nakamura Y, and Yasuo T

Subjects
Biomarkers metabolism, Endometrium metabolism, Female, Humans, Syndecan-1 metabolism, Thrombomodulin metabolism, Proteoglycans metabolism, Reproduction physiology, Uterus metabolism
Abstract

Proteoglycans (PGs) are a group of heavily glycosylated proteins that are present throughout the mammalian body and are involved in a wide variety of biological phenomena, including structural maintenance, tissue remodeling, molecular presentation, cell adhesion and signal transmission. Previous studies have revealed an increasing number of roles for PGs in human reproduction. Several PGs are currently utilized or regarded as biomarkers for the diagnosis of certain pathological uterine conditions associated with infertility and obstetrical complications. The aim of this review was to discuss the involvement of PGs in the human uterus in reproductive biology and pathophysiology.

Published
2012
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47. Effects of aging on alpha1-adrenoceptor mechanisms in the isolated mouse aortic preparation.

Author

Tanaka Y, Funabiki M, Michikawa H, and Koike K

Subjects
Adrenergic alpha-Agonists pharmacology, Adrenergic alpha-Antagonists pharmacology, Animals, Dose-Response Relationship, Drug, Gene Expression Regulation genetics, Male, Mice, Mice, Mutant Strains, Muscle Contraction drug effects, Muscle Contraction genetics, Muscle Contraction physiology, Norepinephrine pharmacology, Prazosin pharmacology, Propranolol pharmacology, Receptors, Adrenergic, alpha-1 genetics, Aging physiology, Aorta, Thoracic physiology, Receptors, Adrenergic, alpha-1 physiology
Abstract

The effects of aging on alpha(1)-adrenoceptor (alpha(1)-AR)-mediated contractile response in endothelium-removed aortic preparations isolated from 5- to 40-week-old (5-, 6-, 8-, 10-, 20-, 40-weeks) mice were studied in the presence of propranolol. The potency of noradrenaline, estimated as its pD(2) value, increased with age from 5- to 10-weeks, but decreased thereafter with age from 10- to 40-weeks. However, the affinity of prazosin (pA(2) value) did not change with aging. These results suggest that age-related change in noradrenaline potency is not attributable to the change of drug affinity to alpha(1)-ARs, but is possibly due to drug affinity-unrelated factors such as change of the reserve of alpha(1)-ARs.

Published
2006
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48. Sutureless patch repair for small blowout rupture of the left ventricle after myocardial infarction.

Author

Nishizaki K, Seki T, Fujii A, Nishida Y, Funabiki M, and Morikawa Y

Subjects
Aged, Fibrinogen therapeutic use, Hemostatics therapeutic use, Humans, Male, Myocardial Infarction complications, Treatment Outcome, Collagen therapeutic use, Heart Rupture, Post-Infarction surgery, Prosthesis Implantation methods, Tissue Adhesives therapeutic use
Abstract

Rupture of the left ventricular free wall is one of the most serious complications of myocardial infarction. A 73-year-old man with severe chest pain visited our hospital. Coronary angiography revealed acute myocardial infarction in the territory of the diagonal branch. About six hours after successful percutaneous coronary intervention, the patient fell into cardiogenic shock with chest pain. Echocardiography showed moderate pericardial effusion with a subepicardial hematoma, and percardioentesis led to the diagnosis of free wall rupture. Emergency surgery was performed with the use of intra-aortic balloon pumping. The rupture was a blowout type in a small tear at the anterolateral wall of the left ventricle. We repaired the tear with an off-pump sutureless patch using collagen fleece with fibrinogen-based impregnation (TachoComb) and equinous pericardium with fibrin spray. The patient was free of both re-rupture and pseudoaneurysm postoperatively, and was discharged 20 days after the operation. Considering previously reported various procedures for surgical repair, this technique may be useful if the tear is small.

Published
2004
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