Impact of Oxidative Stress on Age-Associated Decline in Oocyte Developmental Competence

Abstract

Reproductive capacity in women starts to decline beyond their mid-30s and pregnancies in older women result in higher rates of miscarriage with aneuploidy. Age-related decline in fertility is strongly attributed to ovarian aging, diminished ovarian reserves, and decreased developmental competence of oocytes. In this review, we discuss the underlying mechanisms of age-related decline in oocyte quality, focusing on oxidative stress (OS) in oocytes. The primary cause is the accumulation of spontaneous damage to the mitochondria arising from increased reactive oxygen species (ROS) in oocytes, generated by the mitochondria themselves during daily biological metabolism. Mitochondrial dysfunction reduces ATP synthesis and influences the meiotic spindle assembly responsible for chromosomal segregation. Moreover, reproductively aged oocytes produce a decline in the fidelity of the protective mechanisms against ROS, namely the ROS-scavenging metabolism, repair of ROS-damaged DNA, and the proteasome and autophagy system for ROS-damaged proteins. Accordingly, increased ROS and increased vulnerability of oocytes to ROS lead to spindle instability, chromosomal abnormalities, telomere shortening, and reduced developmental competence of aged oocytes.

Imperatorin Ameliorates the Aging-Associated Porcine Oocyte Meiotic Spindle Defects by Reducing Oxidative Stress and Protecting Mitochondrial Function

“…The aging of postovulatory oocytes has a significant negative impact on livestock production. Although the mechanism of aging is not yet fully clear, excessive accumulation of ROS is considered to be a major factor in inducing aging ( Cui et al, 2011 ; Sasaki et al, 2019 ; Tamura et al, 2020 ). Here, our results demonstrated that IMP exhibited antioxidant effects and enhanced aged oocyte quality by reducing ROS accumulation, autophagy, and apoptosis, enhancing mitochondrial function, and subsequently promoting embryonic development ( Figure 8 ).…”

Characterization of the Age-Dependent Changes in Antioxidant Defenses and Protein’s Sulfhydryl/Carbonyl Stress in Human Follicular Fluid

“…From both a scientific and clinical point of view, the analysis of the effects of oxidative stress on female fertility represents a topic of great interest [ 6 , 24 ]. A great deal of research has shown a contributory role of follicular fluid ROS on ovarian aging and consequently, on oocyte quality [ 25 , 26 , 27 ].…”

MicroRNA-Mediated Gene Regulatory Mechanisms in Mammalian Female Reproductive Health

“…Cellular senescence is the biological consequence of aging, implicated in a variety of age-associated diseases. The increased vulnerability of oocytes to age-induced oxidative stress is associated with the attenuation of the efficacy of DNA double-strand break (DSB) repair mechanisms in aged oocytes [ 142 ]. Some studies have been conducted to correlate follicular fluid extracellular miRNA with advanced women age.…”