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Research Paper|Volume 14, Issue 3|pp 1214—1232

Ribosomal DNA methylation in human and mouse oocytes increases with age

Ramya Potabattula1, Tom Trapphoff2, Marcus Dittrich1,3, Kinga Fic4, Grazyna E. Ptak4, Stefan Dieterle2,5, Thomas Haaf1
  • 1Institute of Human Genetics, Julius Maximilians University, Würzburg, Germany
  • 2Fertility Center, Dortmund, Germany
  • 3Department of Bioinformatics, Julius Maximilians University, Würzburg, Germany
  • 4Malopolska Centre of Biotechnology (MCB), Jagiellonian University, Krakow, Poland
  • 5Division of Reproductive Medicine and Infertility, Department of Obstetrics and Gynecology, Witten/Herdecke University, Dortmund, Germany
Received: September 24, 2021Accepted: February 8, 2022Published: February 14, 2022
https://doi.org/10.18632/aging.203891

Copyright: © 2022 Potabattula et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

An age-dependent increase in ribosomal DNA (rDNA) methylation has been observed across a broad spectrum of somatic tissues and the male mammalian germline. Bisulfite pyrosequencing (BPS) was used to determine the methylation levels of the rDNA core promoter and the rDNA upstream control element (UCE) along with two oppositely genomically imprinted control genes (PEG3 and GTL2) in individual human germinal vesicle (GV) oocytes from 90 consenting women undergoing fertility treatment because of male infertility. Apart from a few (4%) oocytes with single imprinting defects (in either PEG3 or GTL2), the analyzed GV oocytes displayed correct imprinting patterns. In 95 GV oocytes from 42 younger women (26-32 years), the mean methylation levels of the rDNA core promoter and UCE were 7.4±4.0% and 9.3±6.1%, respectively. In 79 GV oocytes from 48 older women (33-39 years), methylation levels increased to 9.3±5.3% (P = 0.014) and 11.6±7.4% (P = 0.039), respectively. An age-related increase in oocyte rDNA methylation was also observed in 123 mouse GV oocytes from 29 4-16-months-old animals. Similar to the continuously mitotically dividing male germline, ovarian aging is associated with a gain of rDNA methylation in meiotically arrested oocytes. Oocytes from the same woman can exhibit varying rDNA methylation levels and, by extrapolation, different epigenetic ages.