ArticleCell death and differentiation2019
Transient inhibition of p53 homologs protects ovarian function from two distinct apoptotic pathways triggered by anticancer therapies.
Article in Cell death and differentiation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 90 citations in OpenAlex.
- ABL kinases regulate FGF signaling independent of CRK phosphorylation to prevent Peters anomaly type II.Nature communications · 2026Article
- Exosomes in oncofertility: emerging roles in chemotherapy-induced reproductive damage and fertility preservation.Reproduction & fertility · 2026Review
- DNA damage response signaling in oocytes from an oncofertility perspective†.Biology of reproduction · 2026Review
- Existing and emerging strategies for fertility preservation in female patients with leukemia.Frontiers in endocrinology · 2026Review
- A TAp63alpha truncating variant associated with primary ovarian insufficiency lowers the cellular apoptotic rate.Journal of ovarian research · 2025Article
- Does gonadotoxic chemotherapy deplete the ovarian reserve through activation of primordial follicles?Human reproduction (Oxford, England) · 2025Article
- Primordial Follicle Survival and Changes in Ovarian Vasculature May Be Independently Regulated During Chemotherapy.Endocrinology · 2025Article
- Leukemic Cells Infiltrate the Ovaries Without Damaging Ovarian Reserve in an Acute Myeloid Leukemia Mouse Model.Endocrinology · 2025Article
- AMH protects the ovary from doxorubicin by regulating cell fate and the response to DNA damage.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Single-cell and bulk transcriptional profiling of mouse ovaries reveals novel genes and pathways associated with DNA damage response in oocytes.Developmental biology · 2025Article
- Oocyte death is triggered by the stabilization of TAp63α dimers in response to cisplatin.Cell death & disease · 2024Article
- KIT in oocytes: a key factor for oocyte survival and reproductive lifespan.EBioMedicine · 2024Article
- The role of declining ataxia-telangiectasia-mutated (ATM) function in oocyte aging.Cell death discovery · 2024Article
- Patients with gynecological malignancies are similar to other IVF patients without cancer for clinical and molecular reproductive parameters and DNA damage response pattern.Scientific reports · 2024Article
- Deletion of Fbxw7 in oocytes causes follicle loss and premature ovarian insufficiency in mice.Journal of cellular and molecular medicine · 2024Article
- Sodium thiosulfate does not protect ovarian reserve from cisplatin-induced gonadotoxicity†.Biology of reproduction · 2024Article
- TP63 truncating mutation causes increased cell apoptosis and premature ovarian insufficiency by enhanced transcriptional activation of CLCA2.Journal of ovarian research · 2024Article
- The Dominant Mechanism of Cyclophosphamide-Induced Damage to Ovarian Reserve: Premature Activation or Apoptosis of Primordial Follicles?Reproductive sciences (Thousand Oaks, Calif.) · 2024Review
- Evidence of apoptosis as an early event leading to cyclophosphamide-induced primordial follicle depletion in a prepubertal mouse model.Frontiers in endocrinology · 2024Article
- Molecular Mechanisms Determining Mammalian Oocyte Quality with the Treatment of Cancer Therapy.Advances in anatomy, embryology, and cell biology · 2024Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Platinum-based chemotherapies can result in ovarian insufficiency by reducing the ovarian reserve, a reduction believed to result from apoptosis of immature oocytes via activation/phosphorylation of TAp63α by multiple kinases including CHEK2, CK1, and ABL1. Here we demonstrate that cisplatin (CDDP) induces oocyte apoptosis through a novel pathway and that temporary repression of this pathway fully preserves ovarian function in vivo. Although ABL kinase inhibitors effectively block CDDP-induced apoptosis of oocytes, oocytic ABL1, and ABL2 are dispensable for damage-induced apoptosis. Instead, CDDP activates TAp63α through the ATR > CHEK1 pathway independent of TAp63α hyper-phosphorylation, whereas X-irradiation activates the ATM > CHEK2 > TAp63α-hyper-phosphorylation pathway. Furthermore, oocyte-specific deletion of Trp73 partially protects oocytes from CDDP but not from X-ray, highlighting the fundamental differences of two pathways. Nevertheless, temporary repression of DNA damage response by a kinase inhibitor that attenuates phosphorylation of ATM, ATR, CHEK1, and CHEK2 fully preserves fertility in female mice against CDDP as well as X-ray. Our current study establishes the molecular basis and feasibility of adjuvant therapies to protect ovarian function against two distinctive gonadotoxic therapeutics, CDDP, and ionizing radiation.
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