Melatonin-induced demethylation of antioxidant genes increases antioxidant capacity through RORα in cumulus cells of prepubertal lambs

Fang, Yi; Zhang, Jinlong; Li, Yihai; Guo, Xiaofei; Liu, Jun-Jie; Zhong, Rongzhen; Zhang, Xiaosheng

doi:10.1016/j.freeradbiomed.2018.11.027

Cited by 29 publications

(17 citation statements)

References 72 publications

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“…In addition, melatonin treatment affects oocytes DNA methylation pattern, reversing the effects of oocyte aging [86]. Thus, although we did not find differential protein expression for the antioxidant enzymes, a recent study in lambs showed that melatonin decreased total DNA methylation of SOD1, GPx4 and CAT, favoring the antioxidant capacity [87]. The melatonin-induced epigenetic regulation must be acting in the pulmonary vasculature of the treated lambs, promoting a balanced REDOX state.…”

Section: Discussioncontrasting

confidence: 53%

Antenatal melatonin modulates an enhanced antioxidant/pro-oxidant ratio in pulmonary hypertensive newborn sheep

et al. 2019

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Chronic hypobaric hypoxia during fetal and neonatal life induces neonatal pulmonary hypertension. Hypoxia and oxidative stress are driving this condition, which implies an increase generation of reactive oxygen species (ROS) and/or decreased antioxidant capacity. Melatonin has antioxidant properties that decrease oxidative stress and improves pulmonary vascular function when administered postnatally. However, the effects of an antenatal treatment with melatonin in the neonatal pulmonary function and oxidative status are unknown. Therefore, we hypothesized that an antenatal therapy with melatonin improves the pulmonary arterial pressure and antioxidant status in high altitude pulmonary hypertensive neonates. Twelve ewes were bred at high altitude (3600 m); 6 of them were used as a control group (vehicle 1.4% ethanol) and 6 as a melatonin treated group (10 mg d -1 melatonin in vehicle). Treatments were given once daily during the last third of gestation (100–150 days). Lambs were born and raised with their mothers until 12 days old, and neonatal pulmonary arterial pressure and resistance, plasma antioxidant capacity and the lung oxidative status were determined. Furthermore, we measured the pulmonary expression and activity for the antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase, and the oxidative stress markers 8-isoprostanes, 4HNE and nitrotyrosine. Finally, we assessed pulmonary pro-oxidant sources by the expression and function of NADPH oxidase, mitochondria and xanthine oxidase. Melatonin decreased the birth weight. However, melatonin enhanced the plasma antioxidant capacity and decreased the pulmonary antioxidant activity, associated with a diminished oxidative stress during postnatal life. Interestingly, melatonin also decreased ROS generation at the main pro-oxidant sources. Our findings suggest that antenatal administration of melatonin programs an enhanced antioxidant/pro-oxidant status, modulating ROS sources in the postnatal lung.

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Section: Discussioncontrasting

confidence: 53%

Antenatal melatonin modulates an enhanced antioxidant/pro-oxidant ratio in pulmonary hypertensive newborn sheep

et al. 2019

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“…Figure 3 summarizes the mechanism of melatonin that are assumed to improve oocyte maturation and quality based on reports to date. Melatonin membrane receptors (MT1, MT2) are located in oocytes and granulosa cells (cumulus cells) [58][59][60][61]; it would be of great interest to determine the intracellular signaling pathway by which melatonin promotes oocyte maturation and embryo development. While some reports have examined these intracellular processes of melatonin in oocytes [62][63][64][65], the details remain unclear.…”

Section: Oocyte Maturation Embryo Development and Melatoninmentioning

confidence: 99%

“…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

163

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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“…The differential expression of CDK1 indicates that inhibition of TBX2 can promote entry into M phase and the transition from G2 to M phase, thus contributing to mitotic progression in cell division 32,33 . In addition, inhibition of TBX2 may also be associated with D-type cyclins (D1, D2, and D3) and CDK4/6 and disrupt the essential processes for entry into G1 phase 34 45,46 .…”

Section: Discussionmentioning

confidence: 99%

“…Finally, we examined the potential effects of TBX2 inhibition on the expansion and physiological function of cumulus cells. Although the expansion of monolayer cells on a hard surface does not fully reflect cumulus cell expansion, we hypothesized that TBX2 would regulate the cumulus cell contact, as TBX2 has been shown to downregulate key factors affecting cumulus cell expansion, such as PTX3, PTGS2, and HAS2 45,46 .…”

Section: Discussionmentioning

confidence: 99%

TBX2 Regulates Proliferation, Apoptosis, and Cholesterol Generation of Bovine Through Maintaining Mitochondrial Function and Autophagy in Bovine Cumulus Cell

Li¹,

Xie²,

Yu³

et al. 2021

Preprint

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TBX2 is a member of T-box gene family whose members are highly conserved in evolution and encoding genes are involved in the regulation of developmental processes. The encoding genes play an important role in growth and development, but its regulatory effects in bovine cumulus cells are still unclear. In this study, the changes of cell physiological function were detected after TBX2 gene was knocked down. Compared with the control group, when TBX2 was inhibited, the levels of autophagy, apoptosis and reactive oxygen species in cumulus cells were increased, the proliferation, expansion ability and the amount of cholesterol secreted by cells were significantly decreased, and the cell cycle was also disrupted. The results showed that TBX2 could regulate the normal physiological activities of bovine cumulus cells.

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Melatonin-induced demethylation of antioxidant genes increases antioxidant capacity through RORα in cumulus cells of prepubertal lambs

Cited by 29 publications

References 72 publications

Antenatal melatonin modulates an enhanced antioxidant/pro-oxidant ratio in pulmonary hypertensive newborn sheep

Antenatal melatonin modulates an enhanced antioxidant/pro-oxidant ratio in pulmonary hypertensive newborn sheep

Importance of Melatonin in Assisted Reproductive Technology and Ovarian Aging

TBX2 Regulates Proliferation, Apoptosis, and Cholesterol Generation of Bovine Through Maintaining Mitochondrial Function and Autophagy in Bovine Cumulus Cell

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