Development of a treatment for advanced aging infertile patients by suppressing CXCL5 and establish a diagnostic method for embryo aging

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K18172
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Juntendo University (2022); International University of Health and Welfare (2020-2021)
• Principal Investigator: Kawagoe Yuta 順天堂大学, 医学部, 非常勤助教 (10609077)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: CXCL5 / 老化 / 卵子老化 / 老化胚

Outline of Final Research Achievements

In Japan, advanced aging infertile patients account for approximately 60% of all IVF cycles. The cause of aging infertility is a decline of the quality of oocytes and preimplantation embryos. However, the mechanism s of quality decline is not fully understood. We has confirmed that the inflammatory cytokine CXCL5 is highly expressed in blastocysts from aging patients. Therefore, we tried to establish a novel aging biomarker that targeting CXCL5. We also tried to conduct a clinical trial to improve pregnancy rates in aging patients by suppressing CXCL5 secreted from embryos. Cumulus cells were collected from aging patients and CXCL5 was measured. It was confirmed that expression levels of CXCL5 in cumulus cells were correlated with patients age. However, it did not correlate with morphologically grade of embryos. A humanized anti-CXCL5 antibody was produced during this study and is currently in the preparation stage for clinical trials.

Free Research Field

生殖医学

Academic Significance and Societal Importance of the Research Achievements

本研究によって、今までは不可能であった高齢不妊患者の胚の老化の程度を測定できる新規バイオマーカーを確立できる可能性を確認した。今後の継続した観察によって、卵丘細胞でのCXCL5と胚移植後の妊娠率、流産率などに相関関係が見られれば高齢不妊患者の治療がさらに効率的に行える可能性がある。また、本研究期間中に作製したヒト化抗CXCL5抗体は市販されている動物由来の抗体より抗原に対する結合力が高い高性能な抗体であり、今後の臨床試験に期待が持てる。またヒト化抗体のため、安全性に関しても問題なく使用できると考えられ、妊娠率改善効果が見られればこれまでにない新たな治療法になることが考えられる。