Melatonin maintains mitochondrial membrane potential and decreases excessive intracellular Ca2+ levels in immature human oocytes

Liu, Ya‐Jing; Ji, Dongmei; Liu, Zhenbang; Wang, Tianjuan; Xie, Fenfen; Zhang, Zhiguo; Wei, Zhaolian; Zhou, Ping; Cao, Yunxia

doi:10.1016/j.lfs.2019.116810

Cited by 41 publications

(33 citation statements)

References 33 publications

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“…The results of the JC-1 test showed that melatonin prevented effectively the reduction of the mitochondrial membrane potential caused by freezing and oxidation. Pena et al [ 40 ] and Liu et al [ 41 ] also demonstrated the role of melatonin in preserving the mitochondrial membrane potential. The main antioxidant enzymes in the cell are SOD, CAT, and GSH-Px.…”

Section: Discussionmentioning

confidence: 99%

Melatonin Protects Goat Spermatogonial Stem Cells against Oxidative Damage during Cryopreservation by Improving Antioxidant Capacity and Inhibiting Mitochondrial Apoptosis Pathway

Feng

Ren

et al. 2020

Oxidative Medicine and Cellular Longevity

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Spermatogonial stem cells (SSCs) are the only adult stem cells that pass genes to the next generation and can be used in assisted reproductive technology and stem cell therapy. SSC cryopreservation is an important method for the preservation of immature male fertility. However, freezing increases the production of intracellular reactive oxygen species (ROS) and causes oxidative damage to SSCs. The aim of this study was to investigate the effect of melatonin on goat SSCs during cryopreservation and to explore its protective mechanism. We obtained SSCs from dairy goat testes by two-step enzymatic digestion and differential plating. The SSCs were cryopreserved with freezing media containing different melatonin concentrations. The results showed that 10-6 M of melatonin increased significantly the viability, total antioxidant capacity (T-AOC), and mitochondrial membrane potential of frozen-thawed SSCs, while it reduced significantly the ROS level and malondialdehyde (MDA) content ( P < 0.05 ). Further analysis was performed by western blotting, flow cytometry, and transmission electron microscopy (TEM). Melatonin improved significantly the enzyme activity and protein expression of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) ( P < 0.05 ), thereby activating the antioxidant defense system of SSCs. Furthermore, melatonin inhibited significantly the expression of proapoptotic protein (Bax) and increased the expression of antiapoptotic proteins (Bcl-2 and Bcl-XL) ( P < 0.05 ). The mitochondrial apoptosis pathway analysis showed that the addition of melatonin reduced significantly the mitochondrial swelling and vacuolation, and inhibited the release of cytochrome C from mitochondria into the cytoplasm, thereby preventing the activation of caspase-3 ( P < 0.05 ) and inhibiting SSC apoptosis. In addition, melatonin reduced significantly the autophagosome formation and regulated the expression of autophagy-related proteins (LC3-I, LC3-II, P62, Beclin1, and ATG7) ( P < 0.05 ), thereby reversing the freeze-induced excessive autophagy. In summary, melatonin protected goat SSCs during cryopreservation via antioxidant, antiapoptotic, and autophagic regulation.

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Section: Discussionmentioning

confidence: 99%

Melatonin Protects Goat Spermatogonial Stem Cells against Oxidative Damage during Cryopreservation by Improving Antioxidant Capacity and Inhibiting Mitochondrial Apoptosis Pathway

Feng

Ren

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…12 Most recently, our group investigated that serotonin and melatoninergic components were expressed in cultured human ovarian cumulus cells, and melatonin might reduce oxidative stress of human oocytes by ameliorating mitochondrial function. 13 Furthermore, the results from recent studies strongly support the important role of serotonin in the regulation of normal mammary gland tissue and breast cancer. 14 Breast cancer is classified into different subtypes based on the presence of progesterone receptor (PR), estrogen receptor (ER) and growth factor receptor epidermal 2 (HER-2).…”

Section: Introductionmentioning

confidence: 77%

Identification of Serotonin as a Predictive Marker for Breast Cancer Patients

Xie

Wang

et al. 2021

IJGM

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Cumulative evidence has demonstrated that breast cancer was the most commonly diagnosed cancer in women. Despite growing evidence for a link between serotonin and tumorigenesis, research on the expression of serotoninergic systems in the human breast cancer cell and tissue has only rarely been reported. Methods: First, immunofluorescence staining, ELISA and Western blotting were used to detect serotonin and melatoninergic systems in various breast cancer cell types. Then, serotonin expression was evaluated in the cultures of TPBC cell line BT-474 and TNBC cell line MDA-MB-231 using immunofluorescence assay. To further explore the diagnostic role of serotonin in breast cancer, serotonin expression was conducted in the TPBC and TNBC tumor sections by immunostaining analysis. Results: Our results suggested that both human breast cancer cells and human breast epithelial cell line could synthesize serotonin and melatonin. Unlike melatonin, serotonin levels varied significantly between human breast cancer and breast epithelial cell line (p<0.01). In addition, serotonin N-acetyltransferase (NAT) and acetylserotonin methyltransferase (ASMT), the key enzymes in the pathway of melatonin synthesis from serotonin, were also detectable. In agreement with these findings of human breast cancer cell and human breast epithelial cell line, serotonin expression was also much higher in triple-negative (PR−, ER−, HER-2 − ) breast cancer (TNBC) and triple-positive breast cancer (TPBC) compared to para-carcinoma tissues (PCTs). Conclusion:Here, we provided evidence that the human breast cancer cell (MCF-7, Bcap-37) and human breast epithelial cell (MCF-10A) could synthesize intrinsic serotonin and melatonin, and serotonin expression was higher in the breast cancer tissue compared with PCT. The findings suggested that serotonin might be used as a predictive marker for breast cancer patients.

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“…The beneficial effects of melatonin on in vitro embryo development have been recorded in mice [29], buffalo [30,31], bovine [32,33], ovine [34], porcine [35], and humans [36]. Melatonin improves cytoplasmic maturation of bovine oocytes by improving the normal distribution of organelles and increasing intracellular GSH, ATP levels, and upregulates genes regulating oocytes maturation [33,37], and mitigates mitochondrial DNA damage [17], and increase total antioxidant capacity in mice oocytes [35]. In contrast, in bovine, melatonin supplementation of IVM media did not improve the cleavage and blastocyst rates [38].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, a variety of antioxidants has been used to decrease ROS during the IVEP [11,12]; however, which antioxidant is the most suitable to support the development of buffalo embryos is still undefined. Melatonin ameliorates oocyte OS and improves subsequent in vitro development and decreased apoptosis levels, recovered the integrity of mitochondria, amend the spindle assembly and chromosome alignment in oocytes, and enhances embryo development in bovine [1,13], pigs [14,15], mice [16], and human [17]. In addition, antioxidant Available at www.veterinaryworld.org/Vol.14/January-2021/10.pdf glutathione (GSH) plays an important role in the antioxidant system of cells [18].…”

Section: Introductionmentioning

confidence: 99%

Effect of oxygen tension and antioxidants on the developmental competence of buffalo oocytes cultured in vitro

et al. 2021

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Aim: Oxidative stress (OS) is one of the major disruptors of oocyte developmental competence, which appears due to the imbalance between the production and neutralization of reactive oxygen species (ROS). Materials and Methods: In Experiment 1, buffalo oocytes were in vitro matured, fertilized, and cultured at 38.5°C under 5% CO2 + 20% O2 in standard CO2 incubator (OS) or under 5% O2 + 5% CO2 + 90% N2 (Multi-gas incubator, low O2). In Experiment 2, buffalo cumulus oocytes complexes (COCs) were matured in Basic maturation medium (BMM) composed of TCM199+ 10% FCS+ 10 μg/ml FSH+ 50 μg/ml gentamicin (control group) or in BMM supplemented with 50 μM ascorbic acid (ascorbic acid group) or 3.0 mM glutathione (glutathione group) or 10-5 M melatonin (melatonin group) and cultured at 38.5°C under 20% O2 for 24 h. Matured buffalo oocytes in control, ascorbic acid, or melatonin groups were fertilized and zygotes were cultured for 8 days under the same conditions. Results: In both experiments, maturation, cleavage, and blastocyst rates were recorded. Results showed that culture of buffalo oocytes under low O2 (5% O2) significantly increased maturation, cleavage, and blastocyst rates (p<0.05). Meanwhile, under 20% O2, addition of 10-5 M melatonin or 50 μM ascorbic acid to in vitro maturation (IVM) medium significantly improved cumulus cell expansion, nuclear maturation rates of buffalo oocytes (p<0.05), and increased cleavage and blastocyst rates (p<0.05). Conclusion: About 5% O2 is the optimum condition for in vitro production of buffalo embryos, and addition of 10-5 M melatonin to IVM medium for oocytes cultured under 20% O2 could alleviate the adverse effect of high oxygen tension and increased embryo yield.

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Melatonin maintains mitochondrial membrane potential and decreases excessive intracellular Ca2+ levels in immature human oocytes

Cited by 41 publications

References 33 publications

Melatonin Protects Goat Spermatogonial Stem Cells against Oxidative Damage during Cryopreservation by Improving Antioxidant Capacity and Inhibiting Mitochondrial Apoptosis Pathway

Melatonin Protects Goat Spermatogonial Stem Cells against Oxidative Damage during Cryopreservation by Improving Antioxidant Capacity and Inhibiting Mitochondrial Apoptosis Pathway

Identification of Serotonin as a Predictive Marker for Breast Cancer Patients

Effect of oxygen tension and antioxidants on the developmental competence of buffalo oocytes cultured in vitro

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