Melatonin Improves the Quality of Inferior Bovine Oocytes and Promoted Their Subsequent IVF Embryo Development: Mechanisms and Results

Yang, Minghui; Tao, Jingli; Chai, Menglong; Wu, Hao; Wang, Jing; Li, Guangdong; He, Chao; Xie, Lu; Ji, Pengyun; Dai, Yong; Yang, Liguo; Liu, Guoshi

doi:10.3390/molecules22122059

Cited by 58 publications

(44 citation statements)

References 59 publications

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“…GDF9 and BMP15 are limited to oocyte cytoplasm, and GDF9 and BMP15 addition improves expression of genes related with oocyte maturation and cumulus expansion in porcine oocytes during IVM [53]. Melatonin treatment moderates reduction of relative values of BMP15 and GDF9 mRNA caused by oocyte denudation during IVM in the bovine [6], and also upregulates expression of BMP15 and GDF9 in inferior oocytes, which are beneficial for oocyte maturation and embryo development in cattle [54]. Melatonin supplementation enhances expression of GDF9 gene via melatonin membrane receptors in oocytes, which are beneficial for bovine oocyte IVM [55].…”

Section: Discussionmentioning

confidence: 99%

Effect of Melatonin on the In Vitro Maturation of Porcine Oocytes, Development of Parthenogenetically Activated Embryos, and Expression of Genes Related to the Oocyte Developmental Capability

Yang

Wang

Cui

et al. 2020

Animals

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Melatonin treatment can improve quality and in vitro development of porcine oocytes, but the mechanism of improving quality and developmental competence is not fully understood. In this study, porcine cumulus–oocyte complexes were cultured in TCM199 medium with non-treated (control), 10−5 M luzindole (melatonin receptor antagonist), 10−5 M melatonin, and melatonin + luzindole during in vitro maturation, and parthenogenetically activated (PA) embryos were treated with nothing (control), or 10−5 M melatonin. Cumulus oophorus expansion, oocyte survival rate, first polar body extrusion rate, mitochondrial distribution, and intracellular levels of reactive oxygen species (ROS) and glutathione of oocytes, and cleavage rate and blastocyst rate of the PA embryos were assessed. In addition, expression of growth differentiation factor 9 (GDF9), tumor protein p53 (P53), BCL2 associated X protein (BAX), catalase (CAT), and bone morphogenetic protein 15 (BMP15) were analyzed by real-time quantitative PCR. The results revealed that melatonin treatment not only improved the first polar body extrusion rate and cumulus expansion of oocytes via melatonin receptors, but also enhanced the rates of cleavage and blastocyst formation of PA embryos. Additionally, melatonin treatment significantly increased intraooplasmic level of glutathione independently of melatonin receptors. Furthermore, melatonin supplementation not only significantly enhanced mitochondrial distribution and relative abundances of BMP15 and CAT mRNA, but also decreased intracellular level of ROS and relative abundances of P53 and BAX mRNA of the oocytes. In conclusion, melatonin enhanced the quality and in vitro development of porcine oocytes, which may be related to antioxidant and anti-apoptotic mechanisms.

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Section: Discussionmentioning

confidence: 99%

Effect of Melatonin on the In Vitro Maturation of Porcine Oocytes, Development of Parthenogenetically Activated Embryos, and Expression of Genes Related to the Oocyte Developmental Capability

Yang

Wang

Cui

et al. 2020

Animals

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“…While some reports have examined these intracellular processes of melatonin in oocytes [62][63][64][65], the details remain unclear. It has been reported that melatonin controls the expression of genes related to oocyte maturation including mitochondrial function [53,60,66,67], antioxidative enzymes [53,59,67,68], apoptosis [52,[65][66][67][68][69], cumulus cell expansion [51,61,70], and oocyte maturation factors [61,67]. Furthermore, epigenetic mechanisms such as DNA methylation and histone acetylation have also been reported [59,66,71].…”

Section: Oocyte Maturation Embryo Development and Melatoninmentioning

confidence: 99%

Importance of Melatonin in Assisted Reproductive Technology and Ovarian Aging

Tamura

Jozaki

Tanabe

et al. 2020

IJMS

152

105

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Melatonin is probably produced in all cells but is only secreted by the pineal gland. The pineal secretion of melatonin is determined by the light-dark cycle, and it is only released at night. Melatonin regulates biological rhythms via its receptors located in the suprachiasmatic nuclei of the hypothalamus. Melatonin also has strong antioxidant activities to scavenge free radicals such as reactive oxygen species (ROS). The direct free radical scavenging actions are receptor independent. ROS play an important role in reproductive function including in the ovulatory process. However, excessive ROS can also have an adverse effect on oocytes because of oxidative stress, thereby causing infertility. It is becoming clear that melatonin is located in the ovarian follicular fluid and in the oocytes themselves, which protects these cells from oxidative damage as well as having other beneficial actions in oocyte maturation, fertilization, and embryo development. Trials on humans have investigated the improvement of outcomes of assisted reproductive technology (ART), such as in vitro fertilization and embryo transfer (IVF-ET), by way of administering melatonin to patients suffering from infertility. In addition, clinical research has examined melatonin as an anti-aging molecule via its antioxidative actions, and its relationship with the aging diseases, e.g., Alzheimer's and Parkinson's disease, is also underway. Melatonin may also reduce ovarian aging, which is a major issue in assisted reproductive technology. This review explains the relationship between melatonin and human reproductive function, as well as the clinical applications expected to improve the outcomes of assisted reproductive technology such as IVF, while also discussing possibilities for melatonin in preventing ovarian aging.

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“…Under the situations in which the cells require ATP for their biological activities including in embryo development (143)(144)(145), or under the situation of ATP production deficiency caused by mitochondrial dysfunctions or other insults, melatonin always promotes ATP production. For example, melatonin improves aging-related ATP deficiency in cybrids (96), restores the normal ATP production in a parkinsonian phenotype zebra fish which express high oxidative stress (88) and increases ATP levels in neural stem cells (NSCs) which require high energy to differentiate into oligodendrocytes and neurons (146).…”

Section: 3melatonin On Atp Production In Mitochondriamentioning

confidence: 99%

Mitochondria: the birth place, battle ground and the site of melatonin metabolism in cells

2019

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It was a surprising discovery when mitochondria, as the power houses of cells, were also found to synthesize the potent mitochondrial targeted antioxidant, melatonin. The melatonin synthetic enzyme serotonin N-acetyltransferase (SNAT) was found in matrix and also in the intermembrane space of mitochondria. We hypothesize that the melatonin synthesis occurs in the matrix due to substrate (N-acetyl co-enzyme A) availability while the intermembrane space may serve as the recycling pool of SNAT to regulate the melatonin circadian rhythm. Another surprise was that the melatonin membrane receptors, including MT1 and MT2, were also present in mitochondria. The protective effects of melatonin against neuronal injury induced by brain ischemia/reperfusion were proven to be mainly mediated by mitochondrial melatonin receptors rather than the cell surface membrane receptors which is contrary to the classical principle. In addition, melatonin metabolic enzyme has also been identified in the mitochondria. This enzyme can convert melatonin to N-acetylserotonin to strengthen the antitumor effects of melatonin. Thus, mitochondria are the generator, battle ground and metabolic sites of melatonin. The biological significance of the strong association between mitochondria and melatonin should be intensively investigated.

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Melatonin Improves the Quality of Inferior Bovine Oocytes and Promoted Their Subsequent IVF Embryo Development: Mechanisms and Results

Cited by 58 publications

References 59 publications

Effect of Melatonin on the In Vitro Maturation of Porcine Oocytes, Development of Parthenogenetically Activated Embryos, and Expression of Genes Related to the Oocyte Developmental Capability

Effect of Melatonin on the In Vitro Maturation of Porcine Oocytes, Development of Parthenogenetically Activated Embryos, and Expression of Genes Related to the Oocyte Developmental Capability

Importance of Melatonin in Assisted Reproductive Technology and Ovarian Aging

Mitochondria: the birth place, battle ground and the site of melatonin metabolism in cells

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