Oxidative Stress Induces Telomere Dysfunction and Shortening in Human Oocytes of Advanced Age Donors.

Paweł Kordowitzki

doi:10.3390/cells10081866

Abstract

Research from the past decades provided strong evidence that in humans the pool of oocytes starts to decline already before the birth of a female individual, and from menarche to menopause the oocyte is exposed to different environmental stimuli. Since more and more women of the 21st century in developed countries wish to postpone the first pregnancy to their thirties, higher rates of miscarriage and chromosomal non-disjunction might occur. In oocytes of advanced maternal age, meaning above 35 years of age, characteristics such as chromosomal instabilities/abnormalities, spindle defects, decreased mitochondrial function and telomere shortening become more prevalent than in younger counterparts. Telomere attrition belongs to the so-called “hallmarks of aging” which are also relevant for the female germ-line cells. In oocytes, telomeres shorten with advancing maternal age due to the effects of reactive oxygen species and not upon replicative senescence, similar to how it is common in dividing cells.

Highlights

Telomere attrition and dysfunction are recognized as a hallmark of aging [1] since they are well-established phenomena contributing to organismal aging and telomere homeostasis is a contributor to other processes of aging, too
Potential explanations were provided on how elevated reactive oxygen species (ROS) alter telomere length homeostasis and biology, and there is no doubt that in human oocytes oxidative telomeric DNA damage appears to be the most relevant cause
Some questions still remain unelucidated, and future studies on oocytes could aim to reveal if changes in telomere length and function upon ROS are induced directly or indirectly

Summary

Introduction

Telomere attrition and dysfunction are recognized as a hallmark of aging [1] since they are well-established phenomena contributing to organismal aging and telomere homeostasis is a contributor to other processes of aging, too. The implication of telomere biology in oocyte aging and women’s fertility is barely starting to be unveiled. Researchers provided evidence that telomere dysfunction and the decreasing activity of the telomerase in ovarian cell types and oocytes is a common property of women’s sub-and infertility with regards to advanced maternal age [4]. In this commentary piece, the most recent knowledge about the correlation between ROS, telomere dysfunction and chromosome instability in oocytes of women will be provided since age-related fertility decline could represent an interesting model to study fundamental phenomena contributing to organismal aging in humans

Telomeres and the Aging Oocyte

Conclusions and Final Remarks