ArticleScientific reports2021
Individual-oocyte transcriptomic analysis shows that genotoxic chemotherapy depletes human primordial follicle reserve in vivo by triggering proapoptotic pathways without growth activation.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- Beyond apoptosis: evidence of other regulated cell death pathways in the ovary throughout development and life.Human reproduction update · 2023Pooled it
- The role of anti-Müllerian hormone as a therapeutic agent to preserve the ovarian follicle pool during chemotherapy.Journal of assisted reproduction and genetics · 2026Review
- Technological Advances of Cryopreservation in Ovarian Tissue for Female Children: Exploring the Molecular Insights and Mechanisms.International journal of molecular sciences · 2026Review
- hAECs restore follicular development in premature ovarian insufficiency via IGFBP2/IGF1R-mediated intercellular communication.Stem cell research & therapy · 2026Article
- Female fertility preservation: 25 years of progress, expanding indications and future prospects.Human reproduction update · 2026Review
- DNA damage response signaling in oocytes from an oncofertility perspective†.Biology of reproduction · 2026Review
- Fertility under fire: how chemotherapy harms the ovaries and the science fighting back?Journal of ovarian research · 2026Review
- Retinoic Acid and Calcitriol Protect Mouse Primordial Follicles from Cyclophosphamide Treatment-Induced Apoptosis.Antioxidants (Basel, Switzerland) · 2026Article
- A Two-Hit Hypothesis for Chemotherapy-Induced Primary Ovarian Insufficiency in Asian Populations: A Population-Specific Mechanistic Framework Linking Genetic Susceptibility and Cytotoxic Stress via the PI3K-AKT-FOXO3 Axis.BioMed research international · 2026Review
- Proteomic profiling reveals the molecular signatures of chemotherapy-induced human ovarian damage.Human reproduction (Oxford, England) · 2025Article
- Pituitary extract supplementation enhances follicular survival and gonadotropin receptor expression in vitrified ovarian tissue of Aceh cattle, Indonesia.Veterinary world · 2025Article
- Three-dimensional visualisation of human ovarian follicles using a whole-mount immunolabelling and optical tissue clearing method.Reproduction & fertility · 2025Article
- Reply: Are transitional primordial follicles stationing in the human ovary?Human reproduction (Oxford, England) · 2025Article
- Fertility Protection in Female Cancer Patients: From Molecular Mechanisms of Gonadotoxic Therapies to Pharmacotherapeutic Possibilities.International journal of molecular sciences · 2025Review
- Classification system of human ovarian follicle morphology: recommendations of the National Institute of Child Health and Human Development - sponsored ovarian nomenclature workshop.Fertility and sterility · 2025Article
- Does gonadotoxic chemotherapy deplete the ovarian reserve through activation of primordial follicles?Human reproduction (Oxford, England) · 2025Article
- Review
- Pyrroloquinoline quinone promotes human mesenchymal stem cell-derived mitochondria to improve premature ovarian insufficiency in mice through the SIRT1/ATM/p53 pathway.Stem cell research & therapy · 2024Article
- 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
- Evidence of apoptosis as an early event leading to cyclophosphamide-induced primordial follicle depletion in a prepubertal mouse model.Frontiers in endocrinology · 2024Article
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8 authors at 1 institution in 1 country.
Funding
Abstract
Gonadotoxic chemotherapeutics, such as cyclophosphamide, can cause early menopause and infertility in women. Earlier histological studies showed ovarian reserve depletion via severe DNA damage and apoptosis, but others suggested activation of PI3K/PTEN/Akt pathway and follicle 'burn-out' as a cause. Using a human ovarian xenograft model, we performed single-cell RNA-sequencing on laser-captured individual primordial follicle oocytes 12 h after a single cyclophosphamide injection to determine the mechanisms of acute follicle loss after gonadotoxic chemotherapy. RNA-sequencing showed 190 differentially expressed genes between the cyclophosphamide- and vehicle-exposed oocytes. Ingenuity Pathway Analysis predicted a significant decrease in the expression of anti-apoptotic pro-Akt PECAM1 (p = 2.13E-09), IKBKE (p = 0.0001), and ANGPT1 (p = 0.003), and reduced activation of PI3K/PTEN/Akt after cyclophosphamide. The qRT-PCR and immunostaining confirmed that in primordial follicle oocytes, cyclophosphamide did not change the expressions of Akt (p = 0.9), rpS6 (p = 0.3), Foxo3a (p = 0.12) and anti-apoptotic Bcl2 (p = 0.17), nor affect their phosphorylation status. There was significantly increased DNA damage by γH2AX (p = 0.0002) and apoptosis by active-caspase-3 (p = 0.0001) staining in the primordial follicles and no change in the growing follicles 12 h after chemotherapy. These data support that the mechanism of acute follicle loss by cyclophosphamide is via apoptosis, rather than growth activation of primordial follicle oocytes in the human ovary.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.