Articles
Vol. 70 No. 2 (2026)
Senolytics alleviate cyclophosphamide-induced premature ovarian insufficiency by eliminating senescent cells
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Published: 21 April 2026
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Alkylating agents, particularly cyclophosphamide (CY), are known for their high toxicity, which can lead to iatrogenic premature ovarian insufficiency (POI) and infertility in young cancer survivors. Currently, effective prevention and treatment strategies remain limited. Given that chemotherapy induces cellular senescence, we investigated the therapeutic potential of dasatinib (D) and quercetin (Q), a senolytic combination known to eliminate senescent cells. Using a CY-induced murine model of ovarian injury, we found that CY treatment increased the accumulation of senescent cells in the ovaries. The resulting senescence-associated secretory phenotype (SASP) led to a deterioration of the ovarian microenvironment, characterized by increased follicular atresia and a decline in follicle quantity, ultimately culminating in POI. Our findings demonstrate that DQ therapy effectively mitigated CY-induced damage by clearing senescent cells and reducing SASP secretion. Clinically, DQ administration restored sex hormone levels and regularity of the estrous cycle, resulting in an overall increase in follicle numbers across all developmental stages. Furthermore, DQ treatment significantly normalized estrous cyclicity, restoring regular cycles in 60% of the CY+DQ mice compared to only ~15% in the CY-alone group (p<0.0001). RNA sequencing analysis revealed that DQ treatment upregulated Pagr1a, a gene associated with extraembryonic development, while downregulating genes involved in senescence induction (Itgb3, Wnt10b, Vegfa) and immune function (A2m, Ccl21d). These results suggest that senescent cells drive CY-induced ovarian damage and that DQ represents a promising therapeutic strategy for preserving the ovarian reserve and endocrine function in female cancer patients.
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Ethics Approval
This study was approved by the Experimental Animal Ethics Committee at Peking University People's HospitalCRediT authorship contribution
Xin Yang, Huina Su, study designing, data interpretation. Huina Su, Ruiqiong Ma, Dehui Su, Cheng Tan, Ye Zhu, experiments and analysis performing. Huina Su, Ruiqiong Ma, analysis and interpretation of data. Huina Su, writing - original draft. All authors made a substantive intellectual contribution, read and approved the final version of the manuscript, agreed to be accountable for all aspects of the work.
Supporting Agencies
National Natural Science Foundation of ChinaData Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
How to Cite
1.
Su H, Ma R, Su D, Tan C, Zhu Y, Yang X. Senolytics alleviate cyclophosphamide-induced premature ovarian insufficiency by eliminating senescent cells. Eur J Histochem [Internet]. 2026 Apr. 21 [cited 2026 Apr. 22];70(2). Available from: https://www.ejh.it/ejh/article/view/4537
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