Oocyte Aging: A Multifactorial Phenomenon in A Unique Cell

Abstract

The oocyte is considered to be the largest cell in mammalian species. Women hoping to become pregnant face a ticking biological clock. This is becoming increasingly challenging as an increase in life expectancy is accompanied by the tendency to conceive at older ages. With advancing maternal age, the fertilized egg will exhibit lower quality and developmental competence, which contributes to increased chances of miscarriage due to several causes such as aneuploidy, oxidative stress, epigenetics, or metabolic disorders. In particular, heterochromatin in oocytes and with it, the DNA methylation landscape undergoes changes. Further, obesity is a well-known and ever-increasing global problem as it is associated with several metabolic disorders. More importantly, both obesity and aging negatively affect female reproduction. However, among women, there is immense variability in age-related decline of oocytes’ quantity, developmental competence, or quality. Herein, the relevance of obesity and DNA-methylation will be discussed as these aspects have a tremendous effect on female fertility, and it is a topic of continuous and widespread interest that has yet to be fully addressed for the mammalian oocyte.

What is driving the global decline of human fertility? Need for a multidisciplinary approach to the underlying mechanisms

“…Unfortunately, the issue for ageing women is not failed fertilization but a loss of developmental potential on the part of their eggs as a consequence of ∼40 years exposure to environmental and lifestyle factors that compromise the capacity of this single cell to be fertilized and develop into a new individual. This functional decline in the oocyte's developmental potential involves a variety of mechanisms including oxidative stress and aneuploidy that cannot be reversed by ART—even though many couples mistakenly believe it can ( 108 – 112 ).…”

Ovarian aging: energy metabolism of oocytes

“…Additionally, RNA epitranscriptomes significantly impact oocyte quality [207][208][209][210][211][212][213]. The epigenome of oocytes changes with age, potentially contributing to the decline in oocyte quality associated with aging [206,[214][215][216][217][218]. Epigenetics can also reshape cellular metabolism by participating in metabolic reprogramming through the regulation of metabolic enzymes and upstream regulator expression and function.…”

Population decline: where demography, social science, and biology intersect

“…Delayed childbearing is a particular problem for our species because women rapidly lose their fertility after the age of 36. This decline in fertility is largely due to a loss of developmental potential on the part of the oocyte due to high levels of oxidative stress and the onset of aneuploidy in a majority of eggs ( Mikwar et al 2020 , Jaswa et al 2021 , Aitken et al 2022 , Kordowitzki et al 2024 ). Unfortunately, such age-dependent infertility cannot be rescued by the ART industry and, as a result, live birth rates following assisted conception show the same decline with maternal age as we see with natural conceptions ( Padilla & Garcia 1989 ).…”