Analysis of mechanism of stem cell aging in endometrium

• Project/Area Number: 18K19618
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
• Research Institution: Kyushu University
• Principal Investigator: kato kiyoko 九州大学, 医学研究院, 教授 (10253527)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2019: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 子宮内膜 / 細胞老化 / 幹細胞 / 不妊症 / 炎症 / サイトカイン / 老化 / 不妊 / 着床

Outline of Final Research Achievements

Gene expression in uteri obtained fromC57BL/6 mice at 5, 8 and 60-75 (aged) weeks of age, was analyzed in duplicate by RNA-sequencing and compared. Three genes expressing the pro-inflammatory cytokines were identified as markers for uterine aging.Protein expression levels of the these genes in their 40’s were significantly higher than those for patients in their 20’s.
Human endometrial stromal cells (hESCs) were isolated from endometrial tissues sampled at oocyte retrieval during the proliferative phase from women undergoing infertility treatment.hESCs from non-receptive patients exhibited significantly higher (p<0.01) proportions of senescent cells, mRNA expressions of CDKN2A and CDKN1A transcripts (p<0.01), and expressions of genes encoding the senescence-associated secretory phenotype (p<0.05). hESCs from receptive patients had significantly higher (p<0.01) mRNA expressions of ABCG2 and ALDH1A1 transcripts.

Academic Significance and Societal Importance of the Research Achievements

加齢とともに不妊症の数が増加してくる。多くの場合、卵の老化が原因とされているが、若い年代でも不妊患者は一定の割合で存在し着床障害の関与が示唆されるが、その詳細は不明である。本研究は、マウスやヒトでの子宮内膜を用いて、加齢による生物学的老化と細胞老化誘導という機能的老化の面から解析したところ、いくつかの共通した炎症性サイトカインの関与がみとめられた。この結果を生殖医療の研究・治療応用につなげていくことは学術的および社会的にも意義があると考える。

Research Products

• [Journal Article] Contribution of senescence in human endometrial stromal cells during proliferative phase to embryo receptivity (2020)
  • Author(s): Tomari H, Kawamura T, Asanoma K, Egashira K, Kawamura K, Honjo K, Nagata Y, Kato K
  • Journal Title: Biology of Reproduction Volume: - Issue: 1 Pages: 104-113
  • DOI: 10.1093/biolre/ioaa044
  • NAID: 120007044566
  • Peer Reviewed
• [Journal Article] Placenta-specific epimutation at H19-DMR among common pregnancy complications: its frequency and effect on the expression patterns of H19 and IGF2 (2019)
  • Author(s): Yamaguchi Yuko、Tayama Chiharu、Tomikawa Junko、Akaishi Rina、Kamura Hiromi、Matsuoka Kentaro、Wake Norio、Minakami Hisanori、Kato Kiyoko、Yamada Takahiro、Nakabayashi Kazuhiko、Hata Kenichiro
  • Journal Title: Clinical Epigenetics Volume: 11 Issue: 1 Pages: 113-113
  • DOI: 10.1186/s13148-019-0712-3
  • Peer Reviewed / Open Access
• [Journal Article] Placental Elasticity as a New Non-invasive Predictive Marker of Pre-eclampsia. (2019)
  • Author(s): Fujita Y, Ohmaru-Nakanishi T, Sugitani M, Kato K
  • Journal Title: Ultrasound inMed.&Biol. Volume: 45(1) Issue: 1 Pages: 93-97
  • DOI: 10.1016/j.ultrasmedbio.2018.09.007
  • Peer Reviewed
• [Journal Article] Fibrosis in Preeclamptic Placentas Is Associated with Stromal Fibroblasts Activated by the Transforming Growth Factor Beta 1 (TGFB1) Signaling Pathway (2018)
  • Author(s): Ohmaru-Nakanishi T, Asanoma K, Fujikawa M, Fujita Y, Yagi H, Onoyama I, Hidaka N, Sonoda K, Kato K
  • Journal Title: Am J Pathol Volume: 188(3) Issue: 3 Pages: 683-695
  • DOI: 10.1016/j.ajpath.2017.11.008
  • Peer Reviewed
• [Journal Article] Infertility after abdominal trachelectomy. (2018)
  • Author(s): Katsuko Egashira, Kana Hiasa, Natsuko Yokota, Teruhiko Kawamura, Chihiro Minami, Kaoru Okugawa, Hideaki Yahata, Kenzo Sonoda, Kiyoko Kato.
  • Journal Title: Acta Obstetricia et Gynecologica Scandinavica Volume: 97 Issue: 11 Pages: 1358-1364
  • DOI: 10.1111/aogs.13429
  • Peer Reviewed / Open Access
• [Journal Article] Ectopic neurogenesis induced by prenatal antiepileptic drug exposure augments seizure susceptibility in adult mice. (2018)
  • Author(s): Sakai A, Matsuda T, Doi H, Nagaishi Y, Kato K, Nakashima K
  • Journal Title: Proc Natl Acad Sci USA Volume: - Issue: 16 Pages: 4270-4275
  • DOI: 10.1073/pnas.1716479115
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Annual report of the Women's Health Care Committee, Japan Society of Obstetrics and Gynecology, 2018 (2018)
  • Author(s): Kitawaki J, Kato K
  • Journal Title: J Obstet Gynaecol Res. Volume: 45(1) Issue: 1 Pages: 22-29
  • DOI: 10.1111/jog.13803
  • Peer Reviewed
• [Presentation] 摘出卵巣からの未成熟卵回収および IVM-ICSI を行い妊娠に至った1例 (2019)
  • Author(s): 水本 茂利, 長尾 洋三, 水本 真夕, 遠藤 祐子, 江頭 活子, 矢幡 秀昭, 加藤 聖子, 蔵本 武志
  • Organizer: 第76回九州・沖縄生殖医学会
• [Presentation] International Session Poster 53 ART 2（Group 53）; One case of successful ICSI therapy for a patient of Glanzmann thrombasthenia (2019)
  • Author(s): Inoue R, Egashira K, Miyazaki M, Kato K
  • Organizer: 第71回日本産科婦人科学会学術講演会
• [Presentation] 性腺摘出術を施行したアンドロゲン不応症の2例 (2019)
  • Author(s): 磯邉 明子, 蔵本 和孝, 井上 令子, 林 広典, 宮崎 順秀, 江頭 活子, 加藤 聖子
  • Organizer: 第59回日本産科婦人科内視鏡学会学術講演会
• [Presentation] 女性の一生を診る (2019)
  • Author(s): 加藤 聖子
  • Organizer: 第34回日本女性医学学会学術集会
  • Invited
• [Presentation] Oncofertility・妊孕性温存1; 当院における妊孕性温存のとりくみ (2019)
  • Author(s): 磯邉 明子, 井上 令子, 蔵本 和孝, 河村 圭子, 林 広典, 宮崎 順秀, 江頭 活子, 加藤 聖子
  • Organizer: 第64回日本生殖医学会学術講演会・総会