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Abnormal DNA methylation in oocytes could be associated with a decrease in reproductive potential in old mice

  • Epigenetics
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

This study was designed to evaluate DNA methylation and the expression of DNA methyltransferases (Dnmt1, Dnmt3a, Dnmt3b and Dnmt3L) in metaphaseII (MII) oocytes and the DNA methylation of pre-implantation embryos during mouse aging to address whether such aging-related changes are associated with decreased reproductive potential in aged mice.

Methods

Oocytes (MII) from 6 to 8 weeks old female mice are referred to as the ‘young group’; oocytes from the same group that were maintained until 35–40 weeks old are referred to as the ‘old group.’ The oocytes were fertilized both in vitro and in vivo to obtain embryos. The DNA methylation levels in the oocytes (MII) and pre-implantation embryos were assessed using fluorescence staining. The expression levels of the Dnmt genes in the oocytes (MII) were assessed using Western blotting.

Results

The DNA methylation levels in the oocytes and pre-implantation embryos (in vivo and in vitro) decreased significantly during the aging of the mice. The expression levels of all of the examined Dnmt proteins in the old group were lower than young group. Both the cleavage and blastocyst rate were significantly lower in the oocytes of the older mice (69.9 % vs. 80.9 %, P < 0.05; 33.9 % vs. 56.4 %, P < 0.05). The pregnancy rate of the old mice was lower than that of the young mice (46.7 % vs. 100 %, P < 0.05). The stillbirth and fetal malformation rate was significantly higher in the old group than in the young group (17.2 % vs. 2.9 %, P < 0.05).

Conclusions

The decreased expression of Dnmt1, Dnmt3a, Dnmt3b and Dnmt3L in oocytes (MII) and the change of genome-wide DNA methylation in oocytes and pre-implantation embryos due to aging may be related to lower reproductive potential in old female mice.

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Acknowledgments

This work was supported by the National Natural Science Foundation Project of China (No. 30972102); China Agricultural University Graduate Scientific Research and Innovation Special Project (No. kycx09027). We thank Professor William Hohenboken, Professor Tiantian Zhang and Dr. QingGang Meng for proofreading the manuscript.

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Authors and Affiliations

  1. Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture and National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, People’s Republic of China

    Ming-xing Yue, Xiang-wei Fu, Guang-bin Zhou, Yun-peng Hou, Ming DU, Liang Wang & Shi-en Zhu

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  1. Ming-xing Yue
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  7. Shi-en Zhu
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Correspondence to Shi-en Zhu.

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Capsule

Aging caused a significant decrease in the expression of four key Dnmts and genome-wide DNA methylation in oocytes and pre-implantation embryos.

Ming-xing Yue and Xiang-wei Fu contributed equally to this work.

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Yue, Mx., Fu, Xw., Zhou, Gb. et al. Abnormal DNA methylation in oocytes could be associated with a decrease in reproductive potential in old mice. J Assist Reprod Genet 29, 643–650 (2012). https://doi.org/10.1007/s10815-012-9780-4

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  • DOI: https://doi.org/10.1007/s10815-012-9780-4

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