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.

Highlights

  • Multiple potential mechanisms have been suggested to be responsible for the ageassociated decline in oocyte quality, such as mitochondrial dysfunction, epigenetic alterations, DNA damage, and chronic exposure to oxidative stress, which are not discussed in this review

  • It is well-established that spindle relocation from the center to the cortex of the oocyte is guided by the cytoplasmic actin microfilaments [21,22]

  • Abnormalities in the meiotic spindle in oocytes lead to disorders of chromosome segregation and, aneuploidy of the embryo [115], which usually leads to miscarriages or congenital defects in the offspring

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Summary

Introduction

Following great improvement in education and lifestyle, maternal age has significantly increased in developed countries compared with the last few decades, and in parallel, the age at which women have their first child has increased [1]. Multiple potential mechanisms have been suggested to be responsible for the ageassociated decline in oocyte quality, such as mitochondrial dysfunction, epigenetic alterations, DNA damage, and chronic exposure to oxidative stress, which are not discussed in this review. Another crucial factor for the aging-related decline of oocytes is the meiotic spindle apparatus, which has piqued researchers’ interest. Once a follicle bearing the oocyte is selected for ovulation, adequate segregation of chromosomes (euploidy) during mammalian meiosis is crucial for physiological cleavage and early embryonic development after fertilization [8]. The significance of proper meiotic spindle assembly of the mammalian oocyte in advanced maternal age and its importance for chromosome segregation is presented. We describe the aspects related to euploidy relevant for in vitro fertilization (IVF) clinics

Impact of Proper Spindle Formation on Euploidy
After the extrusion of theand firstactive polar extrusionafter of the first polar body,tomeiosis
Effect of Advanced Maternal Age on Chromosomal Segregation Accuracy
Spindle Formation Disturbances and the Clinical Relevance of Aneuploidy
Findings
Conclusions

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