Oxidative stress and ageing of the post-ovulatory oocyte

Abstract

With extended periods of time following ovulation, the metaphase II stage oocyte experiences deterioration in quality referred to as post-ovulatory oocyte ageing. Post-ovulatory ageing occurs both in vivo and in vitro and has been associated with reduced fertilization rates, poor embryo quality, post-implantation errors and abnormalities in the offspring. Although the physiological consequences of post-ovulatory oocyte ageing have largely been established, the molecular mechanisms controlling this process are not well defined. This review analyses the relationships between biochemical changes exhibited by the ageing oocyte and the symptoms associated with the ageing phenotype. We also discuss molecular events that are potentially involved in orchestrating post-ovulatory ageing with a particular focus on the role of oxidative stress. We propose that oxidative stress may act as the initiator for a cascade of events that create the aged oocyte phenotype. Specifically, oxidative stress has the capacity to cause a decline in levels of critical cell cycle factors such as maturation-promoting factor, impair calcium homoeostasis, induce mitochondrial dysfunction and directly damage multiple intracellular components of the oocyte such as lipids, proteins and DNA. Finally, this review addresses current strategies for delaying post-ovulatory oocyte ageing with a particular focus on the potential use of compounds such as caffeine or selected antioxidants in the development of more refined media for the preservation of oocyte integrity during IVF procedures.

MAPK3/1 (ERK1/2) and Myosin Light Chain Kinase in Mammalian Eggs Affect Myosin-II Function and Regulate the Metaphase II State in a Calcium- and Zinc-Dependent Manner1

“…Loss of maintenance of metaphase II arrest and loss of cortical spindle localization occur with extended time after ovulation as the egg quality deteriorates during a process known as postovulatory aging [14,15,90,91]. Postovulatory aging is associated with unsuccessful fertilization and, in instances when aged eggs are fertilized, with poor reproductive outcomes, including pregnancy loss, smaller litter sizes, or in offspring with abnormalities [14,15,90,91].…”

“…Loss of maintenance of metaphase II arrest and loss of cortical spindle localization occur with extended time after ovulation as the egg quality deteriorates during a process known as postovulatory aging [14,15,90,91]. Postovulatory aging is associated with unsuccessful fertilization and, in instances when aged eggs are fertilized, with poor reproductive outcomes, including pregnancy loss, smaller litter sizes, or in offspring with abnormalities [14,15,90,91]. Relevant to the data here, postovulatory aged eggs have reduced MAPK3/1 activity associated with a range of membrane and cortical abnormalities and the above-mentioned propensity to undergo parthenogenetic activation [92][93][94][95][96][97][98][99][100].…”

“…Proper maintenance of metaphase II arrest in unfertilized eggs is also crucial for reproductive success, with failure of eggs to maintain metaphase II arrest being associated with reduced female fertility [4][5][6][7]. Reduced ability to maintain metaphase II arrest is also observed in eggs with down-regulated activity of endogenous meiotic inhibitor 2 (EMI2), CDC25A, or PP2A, with reduced levels of cytosolic zinc, or undergoing postovulatory aging [8][9][10][11][12][13][14][15]. A related crucial component of the metaphase II state is spatial control of the meiotic spindle to maintain spindle integrity and set up the asymmetric cytokinesis of second polar body emission.…”

Maternal age effect on mouse oocytes: new biological insight from proteomic analysis

“…These oocytes had aged up to 1 year inside the ovaries and were analysed immediately after ovulation so as to appreciate the effect of maternal age on the oocyte. This should not be confused with the post-ovulatory ageing of oocytes in the oviduct or in a culture medium (Lord & Aitken 2013). We compared and confronted the quantitative protein data with the predictions of mRNA ageing studies of oocytes and somatic cells.…”

Chemotherapy-Induced Oxidative Stress and Infertility

“…Oxidative stress may induce reproductive dysfunction and infertility especially by deteriorating oocyte quality. It has been well demonstrated that oxidative stress affects oocyte integrity by disruption of the spindle structure (8), premature primordial follicle activation (9), antral follicle destruction and impairing the oocyte fusibility (9), deficit of mitochondria-derived ATP (10) and induction of postovulatory oocyte aging (11). Aerobic cells have been equipped with a complex antioxidative defense system comprising several antioxidant enzymes the most important of which superoxide dismutases (SODs), glutathione peroxidase (GPx), and catalase.…”