The effect of molecular targeted chemotherapies on fertility

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K18683
• 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: St. Marianna University School of Medicine
• Principal Investigator: Shiraishi Eriko 聖マリアンナ医科大学, 医学部, 研究員 (60837011)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 卵巣予備能 / 妊孕性 / 分子標的治療薬

Outline of Final Research Achievements

We investigated molecular targeted chemotherapies that gonadal toxicity unknown. The drugs we investigated were the PARP inhibitor olaparib and the tyrosine kinase inhibitor imatinib. We used mice, olaparib damaged granulosa cells that form follicles in the ovary,adversely affecting hormone production and the outcome of in vitro fertilization. Imatinib also damaged granulosa cells, adversely affecting hormone production and IVF outcomes. However, the effect was limited in short-term administration, and the adverse effects were reversed when similar experiments were performed after a washout period. Imatinib is a drug that is taken for a long period of time, and we are thinking that it is necessary to investigate the effects of long-term administration in the future.

Free Research Field

がん・生殖医療

Academic Significance and Societal Importance of the Research Achievements

若年がん患者が妊孕性温存を検討する際、どの程度性腺毒性があるかという情報が重要となるが、新規抗がん剤、特に分子標的薬の場合は、性腺毒性が不明なものが多く、妊孕性温存をすべきか苦慮することが多い。今回我々は、慢性骨髄性白血病治療薬であるイマチニブと、PARP阻害薬であるオラパリブの卵巣毒性について調査した。両薬剤とも、顆粒膜細胞への悪影響により、卵巣機能を低下させる可能性が示唆された。しかし、休薬期間により悪影響は相殺された。イマチニブは、長期的な内服が必要な薬剤であり、卵巣予備能低下を来す可能性があるため、妊孕性温存を検討することにも意義があると考えられた。