Melatonin protects mouse oocytes from DNA damage by enhancing nonhomologous end-joining repair

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Published on Wednesday, 27 November 2019

Abstract

Mammalian oocytes remain arrested at the first prophase of meiosis in ovarian follicles for an extended period. During this protracted arrest, oocytes are remarkably susceptible to the accumulation of DNA damage.

Melatonin (N-acetyl-5-methoxytryptamine), a hormone secreted by the pineal gland, has diverse effects on various physiological processes. However, the effect of melatonin on DNA damage response in mammalian oocytes has not been explored.

Here, we showed that melatonin protected mouse oocytes from DNA damage induced by double-strand breaks (DSBs) during prophase arrest and subsequently improved oocyte quality. We found that DNA damage during prophase arrest impaired subsequent meiotic maturation and deteriorated oocyte quality, increasing chromosome fragmentation, spindle abnormality, mitochondrial aggregation, and oxidative stress. However, melatonin treatment during DNA damage accumulation at prophase improved meiotic maturation and relieved the quality decline of oocytes.

In addition, melatonin inhibited the accumulation of DNA damage during prophase arrest by reducing the γ-H2AX levels. Although activated ATM levels were decreased by melatonin treatment, the effect of melatonin on DNA damage response was not a direct consequence of ATM inhibition. Instead, melatonin enhanced DNA repair via nonhomologous end-joining (NHEJ) pathway. Interestingly, these actions of melatonin on DNA damage response are receptor-independent in mouse oocytes.

Therefore, our results demonstrated that melatonin protects oocytes from DNA damage during prophase arrest by enhancing DNA repair via NHEJ and subsequently prevents the deterioration of oocyte quality during meiotic maturation.

 

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See also:

- Official Web Site: The Di Bella Method;

- The Di Bella Method (A Fixed Part - Melatonin tablets. From 30-40mg/day up to 200mg/day orally in patients with advanced stage of cancer disease and/or patients without respond to traditional treatments);

- Melatonin with adenosine solubilized in water and stabilized with glycine for oncological treatment - technical preparation, effectivity and clinical findings;

- About Melatonin - In vitro, review and in vivo publications;

- Publication: Melatonin anticancer effects: Review (from Di Bella's Foundation);

- Publication: Key aspects of melatonin physiology: 30 years of research (from Di Bella's Foundation);

- The Synergism of Somatostatin, Melatonin, Vitamins Prolactin and Estrogen Inhibitors Increased Survival, Objective Response and Performance Status In 297 Cases of Breast Cancer;

- Complete objective response, stable for 5 years, with the Di Bella Method, of multiple-metastatic carcinoma of the breast;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma;

- Recurrent Glioblastoma Multiforme (grade IV – WHO 2007): a case of complete objective response achieved by means of the concomitant administration of Somatostatin and Octreotide – Retinoids – Vitamin E – Vitamin D3 – Vitamin C – Melatonin – D2 R agonists (Di Bella Method – DBM) associated with Temozolomide;

- The Di Bella Method DBM improved survival objective response and performance status in a retrospective observational clinical study on 23 tumours of the head and neck;

- Chronic Lymphocytic Leukemia: Long-Lasting Remission with Combination of Cyclophosphamide, Somatostatin, Bromocriptine, Retinoids, Melatonin, and ACTH;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in advanced non-small-cell lung cancer patients with low performance status;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in chemotherapy-pretreated patients with advanced lung adenocarcinoma and low performance status;

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