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Dysregulation of methylation and expression of imprinted genes in oocytes and reproductive tissues in mice of advanced maternal age

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

Abstract

Purpose

To evaluate reproductive outcomes in aged compared to young female mice, and determine associated methylation and expression of imprinted genes in reproductive tissues.

Methods

Fetal, placental, and ovarian tissue were collected on d16.5 of pregnancy from young (4–5 weeks) and aged (15 months) mice. Uterine tissue and in vivo matured oocytes were collected from non-pregnant females. Methylation of imprinted genes was determined by restriction enzyme based assays, and transcript abundance of imprinted and nutrient supply genes were analyzed by quantitative PCR (qPCR).

Results

Maternal age was associated with fetal growth restriction and placental overgrowth. In maternally aged mice, methylation was minimally dysregulated in fetal tissue, while placental tissue showed aberrant methylation and transcript abundance of imprinted genes. Ovarian methylation and gene expression was severely dysregulated, although oocyte gene expression was only minimally altered. Abundance of Kcnq1 transcripts was significantly (P < 0.05) increased in oocytes obtained from aged females compared to young females. Gene expression was also severely dysregulated in the uterus, including nutrient transport genes.

Conclusion

Fetal and placental growth abnormalities correspond to aberrant methylation and gene expression in reproductive tissues from maternally aged mice. Significant alterations in gene expression and methylation in the aged ovary suggests that the follicular environment may be compromised. Aberrant methylation and expression of imprinted genes in the aged uterus may contribute to reduced implantation. Maternal age negatively affects imprinted gene methylation and expression in both germ cells and somatic cells of the reproductive tract, contributing to the reduced fertility observed with advanced maternal age.

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Author information

Authors and Affiliations

  1. National Foundation for Fertility Research, 10290 RidgeGate Circle, Lone Tree, CO, 80124, USA

    M. Paczkowski & R. L. Krisher

  2. Colorado Center for Reproductive Medicine, 10290 RidgeGate Circle, Lone Tree, CO, 80124, USA

    W. B. Schoolcraft

  3. Baylor Scott & White Healthcare, 2401 S. 31st Street, Temple, TX, 76508, USA

    M. Paczkowski

Authors
  1. M. Paczkowski
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  2. W. B. Schoolcraft
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  3. R. L. Krisher
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Corresponding author

Correspondence to M. Paczkowski.

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Capsule Maternal age dysregulates the methylation and expression patterns of imprinted genes in reproductive tissues of mice, resulting in abnormal fetal and placental development.

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Paczkowski, M., Schoolcraft, W.B. & Krisher, R.L. Dysregulation of methylation and expression of imprinted genes in oocytes and reproductive tissues in mice of advanced maternal age. J Assist Reprod Genet 32, 713–723 (2015). https://doi.org/10.1007/s10815-015-0463-9

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  • DOI: https://doi.org/10.1007/s10815-015-0463-9

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