Analysis of epigenetic marks in human preimplantation embryos produced with assited reproductive technology

• Project/Area Number: 22591817
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: The University of Tokyo
• Principal Investigator: FUJIMOTO Akihisa 東京大学, 医学部附属病院, 臨床登録医 (00323593)
• Project Period (FY): 2010-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 生殖補助医療 / genomic imprinting / 着床前期胚 / DMR / 体外受精 / 胚盤胞 / インプリンティング / エピジェネシス

Research Abstract

To evaluate the relationship between assisted reproductive technology (ART) and genomic imprinting, differentially-methylated regions (DMR) of two imprinting genes-H19 and PEG1-were analyzed in single blastocyst produced by ART. The frozen embryos at day3 or day5, use of which for research had been approved by the parents, were thawed and incubated in blastocyst medium. Genomic DNA samples were extracted from only high-grade blastocysts. Then the DMRs of the two genes were amplified with polymerase chain reaction, cut with restriction enzymes, and the ratios of methylated / unmethylated alleles were evaluated.
All the blastocysts examined in this study showed normal methylation patterns of DMRs of two imprinting genes.

Research Products

• [Journal Article] Concomitant ovarian drilling and oocyte retrieval by laparoendoscopic single-site surgery led to live birth using in vitro maturation of oocyte and transfer of frozen-thawed blastocyst in woman with polycystic ovary syndrome (2014)
  • Author(s): Hirata T, Fujimoto A, Koga K, Wada-Hiraike O, Fujii T, Osuga Y
  • Journal Title: J Obstet Gynaecol Res Volume: 40(5) Pages: 1431-5
• [Journal Article] Increased risk of placenta previa is associated with endometriosis and tubal factor infertility in assisted reproductive technology (ART) pregnancy (2013)
  • Author(s): Takemura Y,Osuga Y, Fujimoto A, Oi N, Tsutsumi R, Koizumi M, Harada M, Yano T, Taketani Y
  • Journal Title: Gynecological Endocrinology Volume: 29(2) Pages: 113-5
• [Journal Article] Müllerian cyst of the uterus treated with laparoscopy and diagnosed using immunohistology (2013)
  • Author(s): Nakae H, Osuga Y, Fujimoto A, Nakagawa S, Ichinose M, Yano T, Taketani Y
  • Journal Title: J Obstet Gynaecol Res Volume: 39(1) Pages: 430-3
• [Journal Article] The influence of infertility treatment on the prognosis of endometrial cancer and atypical complex endometrial hyperplasia (2013)
  • Author(s): Ichinose M, Fujimoto A, Osuga Y, Minaguchi T, Kawana K, Yaho T, Kozuma S
  • Journal Title: Int J Gynecol Cancer Volume: 23(2) Pages: 288-93
• [Journal Article] Laparoendoscopic single-site concomitant surgery for gallstones and a giant ovarian teratoma (2013)
  • Author(s): Fujimoto A, Osuga Y, Sakurabashi A, Hisatomi S, Kaneko J, Hasegawa K, Yano T, Kokudo N, Kozuma S
  • Journal Title: Asian J Endosc Surg Volume: 6(3) Pages: 223-5
• [Journal Article] Predictive factors for recurrence of ovarian mature cystic teratomas after surgical excision (2013)
  • Author(s): Harada M, Osuga Y, Fujimoto A, Fujimoto A, Fujii T, Yano T, Kozuma S
  • Journal Title: Eur J Obstet Gynecol Reprod Biol Volume: 171(2) Pages: 325-8
• [Journal Article] Factors that predict poor clinical course among patients hospitalized with pelvic inflammatory disease (2013)
  • Author(s): Terao M, Koga K, Fujimoto A, Wada-Hiraike O, Osuga Y, Yano T, Kozuma S
  • Journal Title: J Obstet Gynaecol Res Volume: 40 Issue: 2 Pages: 495
  • DOI: 10.1111/jog.12189
  • Peer Reviewed
• [Journal Article] Predictive factors for recurrence of ovarian mature cystic teratomas after surgical excision (2013)
  • Author(s): Harada M, Osuga Y, Fujimoto A, Fujimoto A, Fujii T, Yano T, Kozuma S.
  • Journal Title: Eur J Obstet Gynecol Reprod Biol. Volume: 171 Issue: 2 Pages: 325
  • DOI: 10.1016/j.ejogrb.2013.09.004
  • Peer Reviewed
• [Journal Article] Laparoendoscopic single-site concomitant surgery for gallstones and a giant ovarian teratoma. (2013)
  • Author(s): Fujimoto A, Osuga Y, Sakurabashi A, Hisatomi S, Kaneko J, Hasegawa K, Yano T, Kokudo N, Kozuma S.
  • Journal Title: Asian J Endosc Surg. Volume: 6 Issue: 3 Pages: 223
  • DOI: 10.1111/ases.12019
  • Peer Reviewed
• [Journal Article] The influence of infertility treatment on the prognosis of endometrial cancer and atypical complex endometrial hyperplasia (2013)
  • Author(s): Ichinose M, Fujimoto A, Osuga Y, Minaguchi T, Kawana K, Yaho T, Kozuma S.
  • Journal Title: Int J Gynecol Cancer Volume: 23 Issue: 2 Pages: 288
  • DOI: 10.1097/igc.0b013e31827c18a1
  • Peer Reviewed
• [Journal Article] Increased risk of placenta previa is associated with endometriosis and tubal factor infertility in assisted reproductive technology pregnancy (2013)
  • Author(s): Takemura;Osuga;Fujimoto;Oi;Tsutsumi;Koizumi;Harada;Yano;Taketani .
  • Journal Title: Gynecological Endocrinology Volume: 29 Issue: 2 Pages: 113
  • DOI: 10.3109/09513590.2012.706669
  • Peer Reviewed
• [Journal Article] Alternative strategies to in vitro fertilization/intracytoplasmic sperm injection treatment for aged infertile women Reproductive (2012)
  • Author(s): Isono W, Wada-Hiraike O, Shirane A, Fujimoto A,Osuga Y, Yano T, Taketani Y
  • Journal Title: Medicine and Biology Volume: 11(1) Pages: 69-72
• [Journal Article] Successful pregnancy following low-dose hCG administration in addition to hMG in a patient with hypothalamic amenorrhea due to weight loss (2012)
  • Author(s): Tsutsumi R, Fujimoto A, Osuga Y, Harada M, Takemura Y, Koizumi M, Yano T, Taketani Y
  • Journal Title: Gynecol Endocrinol Volume: 28(6) Pages: 460-2
• [Journal Article] Growth differentiation factor 3 is induced by bone morphogenetic protein 6 (BMP-6) and BMP-7 and increases luteinizing hormone receptor messenger RNA expression in human granulosa cells (2012)
  • Author(s): Shi J, Yoshino O, Osuga Y, Akiyama I, Harada M, Koga K, Fujimoto A, Yano T, Taketani Y
  • Journal Title: Fertil Steril Volume: 97(4) Pages: 979-83
• [Journal Article] The decision-making process for the fate of frozen embryos by Japanese infertile women: a qualitative study (2012)
  • Author(s): Takahashi S, Fujita M, Fujimoto A, Fujiwara T, Yano T, Tsutsumi O, Taketani Y, Akabayashi A
  • Journal Title: BMC Medical Ethics Volume: 13(1) Pages: 9-9
• [Journal Article] Singleton pregnancy outcomes after assisted and non-assisted reproductive technology in infertile patients Reproductive (2012)
  • Author(s): Tsutsumi R, Fujimoto A, Osuga Y, Ooi N, Takemura Y, Koizumi M, Yano Y, Taketani Y
  • Journal Title: Medicine and Biology Volume: 11(3) Pages: 149-153
• [Journal Article] The Localization and Regulation of Proprotein Convertase Subtilisin/Kexin (PCSK) 6 in Human Ovary (2012)
  • Author(s): Akiyama I, Yoshino O, Osuga Y, Shi J, Hirota Y, Hirata T, Harada M, Koga K, Fujimoto A, Yano T, Taketani Y
  • Journal Title: Am J Reprod Immunol Volume: 68(6) Pages: 491-8
• [Journal Article] Growth differentiation factor 3 is induced by bone morphogenetic protein 6 (BMP-6) and BMP-7 and increases luteinizing hormone receptor messenger RNA expression in human granulosa cells (2012)
  • Author(s): Shi J, Yoshino O, Osuga Y, Akiyama I, Harada M, Koga K, Fujimoto A, Yano T, Taketani Y.
  • Journal Title: Fertil Steril. Volume: 97 Issue: 4 Pages: 979
  • DOI: 10.1016/j.fertnstert.2012.01.100
  • Peer Reviewed
• [Journal Article] The Localization and Regulation of Proprotein Convertase Subtilisin/Kexin (PCSK) 6 in Human Ovary (2012)
  • Author(s): Akiyama I, Yoshino O, Osuga Y, Shi J, Hirota Y, Hirata T, Harada M, Koga K, Fujimoto A, Yano T, Taketani Y.
  • Journal Title: Am J Reprod Immunol. Volume: 68 Issue: 6 Pages: 491
  • DOI: 10.1111/aji.12003
  • Peer Reviewed
• [Journal Article] Successful pregnancy following low-dose hCG administration in addition to hMG in a patient with hypothalamic amenorrhea due to weight loss (2012)
  • Author(s): Tsutsumi R, Fujimoto A, Osuga Y, Harada M, Takemura Y, Koizumi M, Yano T, Taketani Y.
  • Journal Title: Gynecol Endocrinol Volume: 28 Issue: 6 Pages: 460
  • DOI: 10.3109/09513590.2011.633650
  • Peer Reviewed
• [Journal Article] The decision-making process for the fate of frozen embryos by Japanese infertile women: A qualitative study (2012)
  • Author(s): Takahashi S, Fujita M, Fujimoto A, Fujiwara T, Yano T, Tsutsumi O, Taketani Y, Akabayashi A.
  • Journal Title: BMC Medical Ethics Volume: 13 Issue: 1 Pages: 9-9
  • DOI: 10.1186/1472-6939-13-9
  • Peer Reviewed
• [Presentation] Thin endometrium is related to low implantation rate of the patients after conservative treatment for endometrial cancer or atypical complex endometrial hyperplasia (2013)
  • Author(s): Fujimoto A, Ichinose M, Morishima K, Tsutsumi R, Harada M, Hirata T, Oishi H, Osuga Y, Yano T, Kozuma S
  • Organizer: 15^<th> World Congress on Human Reproduction
  • Place of Presentation: Venice
• [Presentation] Single incision laparoscopic ovarian drilling combined with immature oocyte retrieval, followed by IVM-ICSI and successful pregnancy (2013)
  • Author(s): Akihisa Fujimoto, Tetsuya Hirata, Nagisa Ooi, Yuko Watanabe, Kaoru Morishima, Miyuki Harada, Hajime Oishi, Yutaka Osuga, Tetsu Yano, Shiro Kozuma
  • Organizer: 15^<th> World Congress on Human Reproduction
  • Place of Presentation: Venice
• [Presentation] 子宮体癌、複雑型子宮内膜異型増殖症に対する子宮温存治療後のART成績に関する検討 (2013)
  • Author(s): 藤本晃久、市瀬茉里、森嶋かほる、堤亮、原田美由紀、平田哲也、大石元、大須賀穣、矢野哲、上妻志郎
  • Organizer: 第65回日本産科婦人科学会
  • Place of Presentation: 札幌
• [Presentation] Prognosis of endometrial cancer and atypical complex endometrial hyperplasia after conservative therapy and infertility treatment (2012)
  • Author(s): A Fujimoto, M Ichinose, Y Osuga, H Oishi, T Hirata, M Harada, A Hasegawa, K Morishima, A Sakuranashi, K Kawana, T Yano, S Kozuma, Y Taketani
  • Organizer: 28^<th> ESHRE Annual Meeting
  • Place of Presentation: Istanbul, Turkey
• [Presentation] Elective single embryo transfer reduces cumulative pregnancy outcome in aged women (2012)
  • Author(s): K Morishima, A Fujimoto, H OIshi, T Hirata, M Harada, A Hasegawa, Y Osuga, T Yano, S Kozuma, Y Taketani
  • Organizer: 28^<th> ESHRE Annual Meeting
  • Place of Presentation: Istanbul, Turkey
• [Presentation] 単孔式腹腔鏡下未熟卵採卵および卵巣多孔術施行後、未熟卵体外培養(IVM)、顕微授精(ICSI)、自然周期による融解胚移植を経て妊娠成立したPCOSの1例 (2012)
  • Author(s): 平田哲也,藤本晃久,大石元,原田美由紀,長谷川亜希子,森嶋かほる,櫻橋彩子,甲賀かをり,平池修,大須賀穣,藤井知行,矢野哲,上妻志郎
  • Organizer: 第57回日本生殖医学会
  • Place of Presentation: 長崎
• [Presentation] 当院におけるSETの現状と適応についての再検討 (2012)
  • Author(s): 森嶋かほる,藤本晃久,大石元,平田哲也,原田美由紀,堤亮,大須賀穣,矢野哲,藤井知行,上妻志郎
  • Organizer: 第57回日本生殖医学会
  • Place of Presentation: 長崎
• [Presentation] 40歳以上の不妊患者におけるARTの予後規定因子の検討 (2012)
  • Author(s): 三宅友子,原田美由紀,藤本晃久,大須賀穣,大石元,平田哲也,長谷川亜希子,藤井知行,矢野哲,上妻志郎
  • Organizer: 第57回日本生殖医学会
  • Place of Presentation: 長崎
• [Presentation] How can we treat aged infertile women? (2012)
  • Author(s): Fujimoto A
  • Organizer: 14^<th> Chongqing ART workshop
  • Place of Presentation: Chongqing, China
• [Presentation] The status of ART in Japan–increasing aged infertile patients (2012)
  • Author(s): Fujimoto A
  • Organizer: 14^<th> Chongqing ART workshop
  • Place of Presentation: Chongqing, China