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Keywords = fertoprotective agents

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18 pages, 1263 KB  
Review
Fertility Protection in Female Cancer Patients: From Molecular Mechanisms of Gonadotoxic Therapies to Pharmacotherapeutic Possibilities
by Weronika Zajączkowska, Maria Buda, Witold Kędzia and Karina Kapczuk
Int. J. Mol. Sci. 2025, 26(15), 7314; https://doi.org/10.3390/ijms26157314 - 29 Jul 2025
Cited by 1 | Viewed by 2871
Abstract
Chemotherapeutic agents and radiotherapy are highly effective in treating malignancies. However, they carry a significant risk of harming the gonads and may lead to endocrine dysfunction and reproductive issues. This review outlines the molecular mechanisms of gonadotoxic therapies, focusing on radiation, alkylating agents, [...] Read more.
Chemotherapeutic agents and radiotherapy are highly effective in treating malignancies. However, they carry a significant risk of harming the gonads and may lead to endocrine dysfunction and reproductive issues. This review outlines the molecular mechanisms of gonadotoxic therapies, focusing on radiation, alkylating agents, and platinum compounds. It discusses the loss of PMFs due to gonadotoxic exposure, including DNA double-strand breaks, oxidative stress, and dysregulated signaling pathways like PI3K/PTEN/Akt/mTOR and TAp63-mediated apoptosis. Furthermore, it explores strategies to mitigate gonadal damage, including GnRH agonists, AMH, imatinib, melatonin, sphingolipid metabolites, G-CSF, mTOR inhibitors, AS101, and LH. These therapies, paired with existing fertility preservation methods, could safeguard reproductive and hormonal functions and improve the quality of life for young cancer patients. Despite the progress made in recent years in understanding gonadotoxic mechanisms, gaps remain due to questionable reliance on mouse models and the lack of models replicating human ovarian dynamics. Long-term studies are vital for wider analyses and exploration of protective strategies based on various animal models and clinical trials. It is essential to verify that these substances do not hinder the anti-cancer effectiveness of treatments or cause lasting DNA changes in granulosa cells, raising the risk of miscarriages and infertility. Full article
(This article belongs to the Section Molecular Oncology)
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23 pages, 727 KB  
Review
Female Oncofertility: Current Understandings, Therapeutic Approaches, Controversies, and Future Perspectives
by Kim Cat Tuyen Vo and Kazuhiro Kawamura
J. Clin. Med. 2021, 10(23), 5690; https://doi.org/10.3390/jcm10235690 - 3 Dec 2021
Cited by 18 | Viewed by 4979
Abstract
Recent advances in early detection and oncological therapies have ameliorated the survival rate of young cancer patients. Yet, ovarian impairment induced by chemotherapy and radiotherapy is still a challenging issue. This review, based on clinical and lab-based studies, summarizes the evidence of gonadotoxicity [...] Read more.
Recent advances in early detection and oncological therapies have ameliorated the survival rate of young cancer patients. Yet, ovarian impairment induced by chemotherapy and radiotherapy is still a challenging issue. This review, based on clinical and lab-based studies, summarizes the evidence of gonadotoxicity of chemoradiotherapy, the recent approaches, ongoing controversies, and future perspectives of fertility preservation (FP) in female patients who have experienced chemo- or radio-therapy. Existing data indicate that chemotherapeutic agents induce DNA alterations and massive follicle activation via the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. Meanwhile, the radiation causes ionizing damage, leading to germ cell loss. In addition to the well-established methods, numerous therapeutic approaches have been suggested, including minimizing the follicle loss in cryopreserved ovarian grafts after transplantation, in vitro activation or in vitro growing of follicles, artificial ovarian development, or fertoprotective adjuvant to prevent ovarian damage from chemotherapy. Some reports have revealed positive outcomes from these therapies, whereas others have demonstrated conflictions. Future perspectives are improving the live birth rate of FP, especially in patients with adverse ovarian reserve, eliminating the risk of malignancy reintroducing, and increasing society’s awareness of FP importance. Full article
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13 pages, 1923 KB  
Article
Crocetin Mitigates Irradiation Injury in an In Vitro Model of the Pubertal Testis: Focus on Biological Effects and Molecular Mechanisms
by Giulia Rossi, Martina Placidi, Chiara Castellini, Francesco Rea, Settimio D'Andrea, Gonzalo Luis Alonso, Giovanni Luca Gravina, Carla Tatone, Giovanna Di Emidio and Anna Maria D’Alessandro
Molecules 2021, 26(6), 1676; https://doi.org/10.3390/molecules26061676 - 17 Mar 2021
Cited by 13 | Viewed by 4401
Abstract
Infertility is a potential side effect of radiotherapy and significantly affects the quality of life for adolescent cancer survivors. Very few studies have addressed in pubertal models the mechanistic events that could be targeted to provide protection from gonadotoxicity and data on potential [...] Read more.
Infertility is a potential side effect of radiotherapy and significantly affects the quality of life for adolescent cancer survivors. Very few studies have addressed in pubertal models the mechanistic events that could be targeted to provide protection from gonadotoxicity and data on potential radioprotective treatments in this peculiar period of life are elusive. In this study, we utilized an in vitro model of the mouse pubertal testis to investigate the efficacy of crocetin to counteract ionizing radiation (IR)-induced injury and potential underlying mechanisms. Present experiments provide evidence that exposure of testis fragments from pubertal mice to 2 Gy X-rays induced extensive structural and cellular damage associated with overexpression of PARP1, PCNA, SOD2 and HuR and decreased levels of SIRT1 and catalase. A twenty-four hr exposure to 50 μM crocetin pre- and post-IR significantly reduced testis injury and modulated the response to DNA damage and oxidative stress. Nevertheless, crocetin treatment did not counteract the radiation-induced changes in the expression of SIRT1, p62 and LC3II. These results increase the knowledge of mechanisms underlying radiation damage in pubertal testis and establish the use of crocetin as a fertoprotective agent against IR deleterious effects in pubertal period. Full article
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19 pages, 1217 KB  
Review
Melatonin and Fertoprotective Adjuvants: Prevention against Premature Ovarian Failure during Chemotherapy
by Hoon Jang, Kwonho Hong and Youngsok Choi
Int. J. Mol. Sci. 2017, 18(6), 1221; https://doi.org/10.3390/ijms18061221 - 7 Jun 2017
Cited by 46 | Viewed by 10363
Abstract
Premature ovarian failure is one of the side effects of chemotherapy in pre-menopausal cancer patients. Preservation of fertility has become increasingly important in improving the quality of life of completely recovered cancer patients. Among the possible strategies for preserving fertility such as ovarian [...] Read more.
Premature ovarian failure is one of the side effects of chemotherapy in pre-menopausal cancer patients. Preservation of fertility has become increasingly important in improving the quality of life of completely recovered cancer patients. Among the possible strategies for preserving fertility such as ovarian tissue cryopreservation, co-treatment with a pharmacological adjuvant is highly effective and poses less of a burden on the human body. Melatonin is generally produced in various tissues and acts as a universally acting antioxidant in cells. Melatonin is now more widely used in various biological processes including treating insomnia and an adjuvant during chemotherapy. In this review, we summarize the information indicating that melatonin may be useful for reducing and preventing premature ovarian failure in chemotherapy-treated female patients. We also mention that many adjuvants other than melatonin are developed and used to inhibit chemotherapy-induced infertility. This information will give us novel insights on the clinical use of melatonin and other agents as fertoprotective adjuvants for female cancer patients. Full article
(This article belongs to the Special Issue Melatonin and Its Analogues: Experimental and Clinical Aspects)
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