Oocyte aging underlies female reproductive aging: biological mechanisms and therapeutic strategies

Abstract

In recent years, postponement of marriage and childbearing in women of reproductive age has led to an increase in the incidence of age-related infertility. The reproductive aging process in women is assumed to occur due to a decrease in both the quantity and quality of the oocytes, with the ultimate result being a decline in fecundity. This age-related decline in fecundity is strongly dependent on oocyte quality, which is critical for fertilization and subsequent embryo development. Aged oocytes display increased chromosomal abnormality and dysfunction of cellular organelles, both of which factor into oocyte quality. In particular, mitochondrial dysfunction has been suggested as a major contributor to the reduction in oocyte quality as well as to chromosomal abnormalities in aged oocytes and embryos. Participation of oxidative stress in the oocyte aging process has been proposed because oxidative stress has the capacity to induce mitochondrial dysfunction and directly damage many intracellular components of the oocytes such as lipids, protein, and DNA. In an attempt to improve mitochondrial function in aged oocytes, several therapeutic strategies have been investigated using both animal models and assisted reproductive technology. Here, we review the biological mechanisms and present status of therapeutic strategies in the female reproductive aging field and indicate possible future therapeutic strategies.

EXOSC10 sculpts the transcriptome during the growth-to-maturation transition in mouse oocytes

“…Among them, 12 transcripts encoded ribosomal proteins, potentially preparing the poly(A) RNA for degradation and/or translation to provide proteins necessary for the growth-tomaturation transition. The other transcripts encoded proteins that were related to mitochondria and protein transport which are involved extensively in oocyte quality control and aging (38). We also observed a dramatic elimination of RNAs during oocyte progression from GV+3hr to the MII stage, consistent with known biological shrinkage of total RNA in maturing oocytes.…”

The role of mitochondrial activity in female fertility and assisted reproductive technologies: overview and current insights

“…Calorie restriction has also been proposed as a conceivable strategy to ameliorate female fertility capacity in selected cases (Igarashi et al, 2015;Tilly and Sinclair, 2013). Experiments in rodents have shown that, when their usual calorie intake is restricted by 40%, the occurrence of germline cell division errors and mitochondrial damage significantly decreases (Selesniemi et al, 2011).…”

Feasibility of deep learning for predicting live birth from a blastocyst image in patients classified by age

“…Oocyte number and quality decrease with advancing age, and patients older than 35 years should receive prompt evaluation for causes of infertility . Aged oocytes display increased chromosomal abnormalities and dysfunction of cellular organelles, both of which factor into oocyte quality . Advanced age is a risk factor for female infertility, pregnancy loss, fetal anomalies, and stillbirth .…”

“…13 Aged oocytes display increased chromosomal abnormalities and dysfunction of cellular organelles, both of which factor into oocyte quality. 14 Advanced age is a risk factor for female infertility, pregnancy loss, fetal anomalies, and stillbirth. 15 Advanced age has a negative effect on fertility.…”