Dynamic expression of DNA methyltransferases (DNMTs) in oocytes and early embryos

Uysal, Fatma; Akkoyunlu, Gökhan; Öztürk, Saffet

doi:10.1016/j.biochi.2015.06.019

Cited by 111 publications

(75 citation statements)

References 114 publications

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“…Notably, oocyte maturation under high NEFA concentrations significantly altered the expression of genes involved in establishing methylation patterns in the matured cumulus oocyte complex, as well as in resultant day 7.5 blastocysts [5, 7]. Cumulus cells from HIGH COMBI-exposed oocytes exhibited down-regulated expression of DNMT3A [7], which is involved in de novo methylation of cytosine residues at CpG sites in oocytes and early preimplantation embryos until embryonic genome activation [8, 9]. This finding also raises the possibility of altered methylation status due to exposure to adverse maternal metabolic conditions.…”

Section: Introductionmentioning

confidence: 99%

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Exposure of bovine oocytes and embryos to elevated non-esterified fatty acid concentrations: integration of epigenetic and transcriptomic signatures in resultant blastocysts

et al. 2016

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BackgroundMetabolic stress associated with negative energy balance in high producing dairy cattle and obesity in women is a risk factor for decreased fertility. Non-esterified fatty acids (NEFA) are involved in this pathogenesis as they jeopardize oocyte and embryo development. Growing evidence indicates that maternal metabolic disorders can disturb epigenetic programming, such as DNA methylation, in the offspring. Oocyte maturation and early embryo development coincide with methylation changes and both are sensitive to adverse environments. Therefore, we investigated whether elevated NEFA concentrations affect establishment and maintenance of DNA methylation in oocytes and embryos, subsequently altering transcriptomic profiles and developmental competence of resultant blastocysts.ResultsBovine oocytes and embryos were exposed to different NEFA concentrations in separate experiments. In the first experiment, oocytes were matured in vitro for 24 h in medium containing: 1) physiological (“BASAL”) concentrations of oleic (OA), palmitic (PA) and stearic (SA) acid or 2) pathophysiological (“HIGH COMBI”) concentrations of OA, PA and SA. In the second experiment, zygotes were cultivated in vitro for 6.5 days under BASAL or HIGH COMBI conditions. Developmental competence was evaluated by assessing cleavage and blastocyst rate. Overall gene expression and DNA methylation of resultant blastocysts were analyzed using microarray. DNA methylation data were re-evaluated by pyrosequencing. HIGH COMBI-exposed oocytes and embryos displayed a lower competence to develop into blastocysts compared to BASAL-exposed counterparts (19.3% compared to 23.2% and 18.2% compared to 25.3%, respectively) (P < 0.05). HIGH COMBI-exposed oocytes and embryos resulted in blastocysts with altered DNA methylation and transcriptomic fingerprints, compared to BASAL-exposed counterparts. Differences in gene expression and methylation were more pronounced after exposure during culture compared to maturation suggesting that zygotes are more susceptible to adverse environments. Main gene networks affected were related to lipid and carbohydrate metabolism, cell death, immune response and metabolic disorders.ConclusionsOverall, high variation in methylation between blastocysts made it difficult to draw conclusions concerning methylation of individual genes, although a clear overview of affected pathways was obtained. This may offer clues regarding the high rate of embryonic loss and metabolic diseases during later life observed in offspring from mothers displaying lipolytic disorders.

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Section: Introductionmentioning

confidence: 99%

“…DNMTs , are crucial for driving appropriate growth and differentiation in the developing embryo, especially during oocyte maturation and early embryo development [9–12]. In the oocyte, an increase in DNA methylation occurs during its growth with the highest level reached at the germinal vesicle stage [13, 14].…”

Section: Introductionmentioning

confidence: 99%

Exposure of bovine oocytes and embryos to elevated non-esterified fatty acid concentrations: integration of epigenetic and transcriptomic signatures in resultant blastocysts

et al. 2016

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“…DNA methylation, a mechanism of epigenetic reprogramming of the genome during embryogenesis [44,45,46], is accomplished through the activities of DNA methyltransferases (DNMTs) [47], which mainly focuses on two different methylation processes: maintenance and de novo , and are catalyzed by DNMT1 and DNMT3a, respectively [48]. The DNMT gene appears to be affected by in vitro culture conditions, which may result in aberrant DNA methylation [48, 49].…”

Section: Discussionmentioning

confidence: 99%

Baicalin increases developmental competence of mouse embryos <i>in vitro</i> by inhibiting cellular apoptosis and modulating <i>HSP70</i> and DNMT expression

Xia

et al. 2016

Journal of Reproduction and Development

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Scutellaria baicalensis has been effectively used in Chinese traditional medicine to prevent miscarriages. However, little information is available on its mechanism of action. This study is designed specifically to reveal how baicalin, the main effective ingredient of S. baicalensis, improves developmental competence of embryos in vitro, using the mouse as a model. Mouse pronuclear embryos were cultured in KSOM medium supplemented with (0, 2, 4 and 8 μg/ml) baicalin. The results demonstrated that in vitro culture conditions significantly decreased the blastocyst developmental rate and blastocyst quality, possibly due to increased cellular stress and apoptosis. Baicalin (4 µg/ml) significantly increased 2- and 4-cell cleavage rates, morula developmental rate, and blastocyst developmental rate and cell number of in vitro-cultured mouse embryos. Moreover, baicalin increased the expression of Gja1, Cdh1, Bcl-2, and Dnmt3a genes, decreased the expression of Dnmt1 gene, and decreased cellular stress and apoptosis as it decreased the expression of HSP70, CASP3, and BAX and increased BCL-2 expression in blastocysts cultured in vitro. In conclusion, baicalin improves developmental competence of in vitro-cultured mouse embryos through inhibition of cellular apoptosis and HSP70 expression, and improvement of DNA methylation.

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“…Due to reports that vitrification/cryopreservation technology causes damage in embryos [3,13,14] the safety of vitrification/cryopreservation for the cryopreservation of human embryos has received extensive attention [15] in this study, we first observed the morphology of testicular development for male mice born from embryos after vitrification/cryopreservation. At PND1-PND3, spermatocytes were located on the medial side of supporting cells and the central part of spermatogenic tubules.…”

Section: Discussionmentioning

confidence: 99%

Development of Testes and Expression of Beta-catenin in Testes Tissue of Mice Born from Vitrified/Cryopreserved Embryos

Liang¹,

Wang²,

Hu³

et al. 2017

JFIV Reprod Med Genet

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Objective: To evaluate the impact of vitrifying embryo from mice on the development of testes of offspring. Materials and methods:This study included 60 male offspring mice, 30 male mice from transferred vitrified embryos and 30 male mice from transferred fresh embryos. We tested the morphology and β-catenin gene expression of testes of difference time after they born. Results:The HE staining results of the testes of the vitrification group and the fresh group showed dark blue staining in the nuclei and varying degrees of red staining in the cytoplasm and fibrous tissue. And there were no significant differences in the morphology of the testis tissues at the different developmental stages between the two groups. With the use of reverse transcription polymerase chain reaction and Western blotting, the data showed that there were no significant differences in the expression of β-catenin in the testes between the two groups of mice at different developmental stages. Conclusion:These data suggest that vitrifying pre-implantation embryos may have no effects on morphology and β-catenin gene expression of the testes of offspring.

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Dynamic expression of DNA methyltransferases (DNMTs) in oocytes and early embryos

Cited by 111 publications

References 114 publications

Exposure of bovine oocytes and embryos to elevated non-esterified fatty acid concentrations: integration of epigenetic and transcriptomic signatures in resultant blastocysts

Exposure of bovine oocytes and embryos to elevated non-esterified fatty acid concentrations: integration of epigenetic and transcriptomic signatures in resultant blastocysts

Baicalin increases developmental competence of mouse embryos <i>in vitro</i> by inhibiting cellular apoptosis and modulating <i>HSP70</i> and DNMT expression

Development of Testes and Expression of Beta-catenin in Testes Tissue of Mice Born from Vitrified/Cryopreserved Embryos

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