ArticleCell death & disease2019
Kinase-independent inhibition of cyclophosphamide-induced pathways protects the ovarian reserve and prolongs fertility.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- Loss of Nemp1 disrupts female meiosis and activates a conserved ATM-CHK2 checkpoint.Nature communications · 2026Article
- Retinoic Acid and Calcitriol Protect Mouse Primordial Follicles from Cyclophosphamide Treatment-Induced Apoptosis.Antioxidants (Basel, Switzerland) · 2026Article
- Combination olaparib and cyclophosphamide cancer therapy exacerbates ovarian reserve depletion in mice with conditional loss ofFrontiers in endocrinology · 2026Article
- Oocyte and embryo developmental competence following small multiple cyclophosphamide dose administrations in prepubertal female mice are comparable to adolescents.Scientific reports · 2025Article
- An updated look into reactive oxygen species and cyclophosphamide-induced ovarian damage.Journal of ovarian research · 2025Review
- Ethanolic Extract of Pomegranate (Animals : an open access journal from MDPI · 2025Article
- Fertility Protection in Female Cancer Patients: From Molecular Mechanisms of Gonadotoxic Therapies to Pharmacotherapeutic Possibilities.International journal of molecular sciences · 2025Review
- Effects of Huluan decotion on cyclophosphamide-induced autoimmune premature ovarian failure in murine models.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2025Article
- Intrinsic differences in mTOR activity mediates lineage-specific responses to cyclophosphamide in mouse and human granulosa cells.Journal of ovarian research · 2025Article
- Comparison of large single and small multiple doses of cyclophosphamide exposure in mice during early prepubertal age on fertility outcome.Scientific reports · 2024Article
- An overview of different methods to establish a murine premature ovarian failure model.Animal models and experimental medicine · 2024Review
- Fertility protective effects of Brillantaisia patula leaf extract against cyclophosphamide-induced ovarian damage in Wistar rats.BMC biotechnology · 2024Article
- The role of declining ataxia-telangiectasia-mutated (ATM) function in oocyte aging.Cell death discovery · 2024Article
- Review
- Rapamycin prevents cyclophosphamide-induced ovarian follicular loss and potentially inhibits tumour proliferation in a breast cancer xenograft mouse model.Human reproduction (Oxford, England) · 2024Article
- Research progress on the prevention and treatment of chemotherapy-induced ovarian damage.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024Review
- Anti-Mullerian hormone attenuates both cyclophosphamide-induced damage and PI3K signalling activation, while rapamycin attenuates only PI3K signalling activation, in human ovarian cortex in vitro.Human reproduction (Oxford, England) · 2024Article
- Protective Effect of Glutathione Administration on Ovarian Function in Female Rats with Cyclophosphamide-Induced Ovarian Damage.Gynecologic and obstetric investigation · 2024Article
- The Dominant Mechanism of Cyclophosphamide-Induced Damage to Ovarian Reserve: Premature Activation or Apoptosis of Primordial Follicles?Reproductive sciences (Thousand Oaks, Calif.) · 2024Review
- A Journey to Reach the Ovary Using Next-Generation Technologies.International journal of molecular sciences · 2023Review
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Authors and funding
8 authors.
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Abstract
Premature ovarian failure and infertility are adverse effects of cancer therapies. The mechanism underlying chemotherapy-mediated depletion of the ovarian reserve remains unclear. Here, we aim to identify the signaling pathways involved in the loss of the ovarian reserve to prevent the damaging effects of chemotherapy. We evaluated the effects of cyclophosphamide, one of the most damaging chemotherapeutic drugs, against follicle reserve. In vivo studies showed that the cyclophosphamide-induced loss of ovarian reserve occurred through a sequential mechanism. Cyclophosphamide exposure induced the activation of both DNAPK-γH2AX-checkpoint kinase 2 (CHK2)-p53/TAp63α isoform and protein kinase B (AKT)-forkhead box O3 (FOXO3a) signaling axes in the nucleus of oocytes. Concomitant administration of an allosteric ABL inhibitor and cyclophosphamide modulated both pathways while protecting the ovarian reserve from chemotherapy assaults. As a consequence, the fertility of the treated mice was prolonged. On the contrary, the administration of an allosteric ABL activator enhanced the lethal effects of cyclophosphamide while shortening mouse fertility. Therefore, kinase-independent inhibition may serve as an effective ovarian-protective strategy in women under chemotherapy.
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