Aneuploidy in mammalian oocytes and the impact of maternal ageing.
Chloe CharalambousAlexandre WebsterMelina SchuhPublished in: Nature reviews. Molecular cell biology (2022)
During fertilization, the egg and the sperm are supposed to contribute precisely one copy of each chromosome to the embryo. However, human eggs frequently contain an incorrect number of chromosomes - a condition termed aneuploidy, which is much more prevalent in eggs than in either sperm or in most somatic cells. In turn, aneuploidy in eggs is a leading cause of infertility, miscarriage and congenital syndromes. Aneuploidy arises as a consequence of aberrant meiosis during egg development from its progenitor cell, the oocyte. In human oocytes, chromosomes often segregate incorrectly. Chromosome segregation errors increase in women from their mid-thirties, leading to even higher levels of aneuploidy in eggs from women of advanced maternal age, ultimately causing age-related infertility. Here, we cover the two main areas that contribute to aneuploidy: (1) factors that influence the fidelity of chromosome segregation in eggs of women from all ages and (2) factors that change in response to reproductive ageing. Recent discoveries reveal new error-causing pathways and present a framework for therapeutic strategies to extend the span of female fertility.
Keyphrases
- pregnancy outcomes
- polycystic ovary syndrome
- endothelial cells
- copy number
- pregnant women
- induced pluripotent stem cells
- insulin resistance
- cervical cancer screening
- type diabetes
- metabolic syndrome
- emergency department
- pluripotent stem cells
- genome wide
- birth weight
- cell cycle arrest
- oxidative stress
- skeletal muscle
- gene expression
- patient safety
- weight loss
- young adults
- weight gain