Oocyte aging-induced Neuronatin (NNAT) hypermethylation affects oocyte quality by impairing glucose transport in porcine

Gao, Yingying; Chen, Li; Wang, Tao; Nie, Zheng‐Wen; Zhang, Xia; Miao, Yi‐Liang

doi:10.1038/srep36008

Cited by 18 publications

(22 citation statements)

References 32 publications

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“…In contrast, the methylation levels of the same site are 0% in untreated oocytes. We observed the similar results in aged oocytes; however, the difference was that it was site 15 that had low level of methylation in fresh porcine oocytes (Gao et al, ). We speculate that specific CpG sites methylation pattern of NNAT are sensitive to different environment.…”

Section: Discussionsupporting

confidence: 73%

“…A). We have previously proved that the expression of NNAT would affect glucose transport (Gao et al, ). So we detected whether NaF affected glucose transport in oocytes treated by NaF.…”

Section: Resultsmentioning

confidence: 96%

“…We have previously reported that the expression of NNAT was declined by elevating DNA methylation, which affected oocyte quality by decreasing the ability of glucose transport in aged oocytes (Gao et al, ). So we speculated that NaF also could induce the hypermethylation of NNAT and decreased their expression, which affected oocyte quality by decreasing the ability of glucose transport in treated oocytes.…”

Section: Discussionmentioning

confidence: 99%

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Sodium fluoride disturbs DNA methylation of NNAT and declines oocyte quality by impairing glucose transport in porcine oocytes

Liu

Nie

Gao

et al. 2017

Environ and Mol Mutagen

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Sodium fluoride (NaF) is used as a medicine to prevent tooth decay; however, excessive NaF could cause a pathological damage to the health. Recent studies showed that NaF impaired mouse oocyte maturation, included of abnormal spindle configuration, actin cap formation, cortical granule-free domain formation, and the following development after fertilization. However, few studies used large animals as models to study the toxicology of NaF on oocytes maturation. We proposed a hypothesis that NaF would affect the nuclear and cytoplasmic maturation of porcine oocytes and DNA methylation pattern of imprinted genes in oocytes. Our results showed that NaF affected cumulus expansion, polar body emission, spindle morphology, cortical granule distribution, early apoptosis, and the following development after parthenogenetic activation during porcine oocyte maturation. Moreover, NaF increased the DNA methylation of NNAT and decreased its expression, which disturbed the glucose transport in oocytes. These results suggest that NaF impairs the porcine oocytes maturation epigenetically, which provides a new toxicological mechanism of NaF on the oocyte maturation. Environ. Mol. Mutagen. 59:223-233, 2018. © 2017 Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 73%

“…A). We have previously proved that the expression of NNAT would affect glucose transport (Gao et al, ). So we detected whether NaF affected glucose transport in oocytes treated by NaF.…”

Section: Resultsmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Sodium fluoride disturbs DNA methylation of NNAT and declines oocyte quality by impairing glucose transport in porcine oocytes

Liu

Nie

Gao

et al. 2017

Environ and Mol Mutagen

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“…Accumulating reports have documented that postovulatory aging of mouse oocytes induces a variety of morphologic and functional changes that impair fertilizing potential, disrupt developmental competence, and increase the likelihood of embryonic resorption (5,6,8,9,(16)(17)(18)(19)(20)(21). DNA methylation of some imprinted genes was also observed to be changed in postovulatory aged mouse oocytes (22).…”

Section: Discussionmentioning

confidence: 99%

Postovulatory aging causes the deterioration of porcine oocytes via induction of oxidative stress

et al. 2018

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Negative effects of postovulatory aging on fertilization ability and subsequent embryo development have been reported in rodents; however, the molecular and cellular changes during this process have not been fully defined. Here, we used porcine oocytes, a model that is physiologically and developmentally similar to humans, to explore the molecular mechanisms that underlie how postovulatory aging affects oocyte quality and fertilization capacity. We found that postovulatory aging caused the morphologic change of porcine oocytes by exhibiting the incompact expansion of cumulus cells and an increased occurrence of fragmentation. Aging also impaired oocyte quality by disrupting organelle structures, including the spindle assembly, actin polymerization, and mitochondrial integrity. Moreover, postovulatory aging led to the abnormal distribution of cortical granules and ovastacin, which, in turn, resulted in defective sperm binding and consequently compromised fertilization potential. Of note, we observed that postovulatory aging induced oxidative stress with a high level of reactive oxygen species and apoptotic rate in oocytes, thereby resulting in the deterioration of critical factors in the maintenance of oocyte quality and fertilization capacity. Taken together, our findings demonstrate that postovulatory aging perturbs a variety of molecular and cellular changes in porcine oocytes by inducing oxidative stress.-Miao, Y., Zhou, C., Cui, Z., Zhang, M., ShiYang, X., Lu, Y., Xiong, B. Postovulatory aging causes the deterioration of porcine oocytes via induction of oxidative stress.

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“…Folate pathway includes two cycles which are closely related with DNA and RNA synthesis and methylation modification respectively (1, 5). Both DNA/RNA synthesis and methylation reaction are crucial for oocyte quality and embryonic development (31)(32)(33). However, does MTX affect the oocyte quality?…”

Section: Discussionmentioning

confidence: 99%

Methotrexate impaired in-vivo matured mouse oocyte quality and the possible mechanisms

Tian

et al. 2020

Preprint

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Abstract Background: Methotrexate (MTX) is an antifolate agent which is widely used in clinic for treating malignancies, rheumatoid arthritis and ectopic pregnancy. As reported, MTX has side effects on gastrointestinal system, nervous system and reproductive system, while its potential damages on oocyte quality are still unclear. It is known that oocyte quality is essential for healthy conception and the forthcoming embryo development. Thus, this work studied the effects of MTX on the oocyte quality. Results: We established MTX model mice by single treatment with 5 mg/Kg MTX. Both morphological and molecular biology studies were performed to assess the in-vivo matured oocytes quality and to analyze the related mechanisms. The in-vivo matured oocytes from MTX-treated mice had poor in-vitro fertilization ability, and the resulting embryo formation rates and blastocyst quality were lower than the control group. We found that the in-vivo matured MTX-treated mouse oocytes displayed abnormal transcript expressions for genes of key enzymes in the folate cycles. MTX increased the rate of abnormal chromosome alignment and affected the regulation of chromosome separation via disrupting the spindle morphology and reducing the mRNA expressions of MAD2 and Sgo1. MTX reduced the DNA methylation levels in the in-vivo matured oocytes, and further studies showed that MTX altered the expressions of DNMT1 and DNMT 3b, and may also affect the levels of the methyl donor and its metabolite. Conclusions: MTX impaired the in-vivo matured mouse oocyte quality by disturbing folate metabolism and affecting chromosome stability and methylation modification.

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Oocyte aging-induced Neuronatin (NNAT) hypermethylation affects oocyte quality by impairing glucose transport in porcine

Cited by 18 publications

References 32 publications

Sodium fluoride disturbs DNA methylation of NNAT and declines oocyte quality by impairing glucose transport in porcine oocytes

Sodium fluoride disturbs DNA methylation of NNAT and declines oocyte quality by impairing glucose transport in porcine oocytes

Postovulatory aging causes the deterioration of porcine oocytes via induction of oxidative stress

Methotrexate impaired in-vivo matured mouse oocyte quality and the possible mechanisms

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