Chromosome Segregation in the Oocyte: What Goes Wrong during Aging

Abstract

Human female fertility and reproductive lifespan decrease significantly with age, resulting in an extended post-reproductive period. The central dogma in human female reproduction contains two important aspects. One is the pool of oocytes in the human ovary (the ovarian reserve; approximately 106 at birth), which diminishes throughout life until menopause around the age of 50 (approximately 103 oocytes) in women. The second is the quality of oocytes, including the correctness of meiotic divisions, among other factors. Notably, the increased rate of sub- and infertility, aneuploidy, miscarriages, and birth defects are associated with advanced maternal age, especially in women above 35 years of age. This postponement is also relevant for human evolution; decades ago, the female aging-related fertility drop was not as important as it is today because women were having their children at a younger age. Spindle assembly is crucial for chromosome segregation during each cell division and oocyte maturation, making it an important event for euploidy. Consequently, aberrations in this segregation process, especially during the first meiotic division in human eggs, can lead to implantation failure or spontaneous abortion. Today, human reproductive medicine is also facing a high prevalence of aneuploidy, even in young females. However, the shift in the reproductive phase of humans and the strong increase in errors make the problem much more dramatic at later stages of the female reproductive phase. Aneuploidy in human eggs could be the result of the non-disjunction of entire chromosomes or sister chromatids during oocyte meiosis, but partial or segmental aneuploidies are also relevant. In this review, we intend to describe the relevance of the spindle apparatus during oocyte maturation for proper chromosome segregation in the context of maternal aging and the female reproductive lifespan.

Resveratrol and SIRT1: Antiaging Cornerstones for Oocytes?

“…The functioning of these two elements is tightly regulated by several external, as well as internal, factors so that they can work together. Recently, the sirtuin family has been presented as one of the most important factors influencing precisely these two processes—mitochondrial function and the course of meiotic division [ 12 , 13 , 14 ]. In particular, SIRT1 is responsible for modulating mitochondrial activity and is one of the protectors against oxidative stress at the ovarian site [ 15 ].…”

Unfertilized oocytes after intracytoplasmic sperm injection and women’s age

“…3 The number of oocytes in the ovarian gradually decreases throughout life until reaching menopause (about 10 6 at birth to about 10³ at menopause). 8 However, there were not significant differences in the mature oocytes rate and fertilization rate between the two age groups (p>0.05) (Table 2). The fertilization rate was not affected by the increasing age of women in IVF and ICSI that demonstrated by previous studies.…”

Effects of follicular output rate on cumulative clinical pregnancy rate and cumulative live birth rate in PCOS patients with different characteristics

“…We know that oocyte quality gradually declines with women aging and the competence of women’s oocytes begins to deteriorate around their third decade ( 35 ). Multiple potential mechanisms may be responsible for this, such as meiotic spindle abnormalities, mitochondrial dysfunction and chronic exposure to oxidative stress, which usually lead to aneuploidy of the embryo and a higher incidence of adverse pregnancy outcomes ( 36 – 39 ). In general, younger women have better oocyte quality, which may somewhat attenuate the impact of FORT on pregnancy outcomes.…”