Mechanisms of Aneuploidy in Human Eggs

Fertility steadily decreases as women age and, by mid-life, women fail to produce healthy eggs. Meiotic chromosomes experience age-related structural changes that may contribute to increasing rates of chromosome segregation errors. Novel error-causing pathways are reported in human oocytes that might explain how a previously undetected alternative segregation pattern arises. Emerging studies provide a better understanding of why oocytes are frequently defective and lead to age-related infertility. Recent studies have found that meiosis in mammalian females is intrinsically error prone, causing high rates of aneuploidy and infertility. Cellular mechanisms responsible for segregating chromosomes are inefficient, affecting females of all ages. Eggs and sperm develop through a specialized cell division called meiosis. During meiosis, the number of chromosomes is reduced by two sequential divisions in preparation for fertilization. In human female meiosis, chromosomes frequently segregate incorrectly, resulting in eggs with an abnormal number of chromosomes. When fertilized, these eggs give rise to aneuploid embryos that usually fail to develop. As women become older, errors in meiosis occur more frequently, resulting in increased risks of infertility, miscarriage, and congenital syndromes, such as Down's syndrome. Here, we review recent studies that identify the mechanisms causing aneuploidy in female meiosis, with a particular emphasis on studies in humans. Eggs and sperm develop through a specialized cell division called meiosis. During meiosis, the number of chromosomes is reduced by two sequential divisions in preparation for fertilization. In human female meiosis, chromosomes frequently segregate incorrectly, resulting in eggs with an abnormal number of chromosomes. When fertilized, these eggs give rise to aneuploid embryos that usually fail to develop. As women become older, errors in meiosis occur more frequently, resulting in increased risks of infertility, miscarriage, and congenital syndromes, such as Down's syndrome. Here, we review recent studies that identify the mechanisms causing aneuploidy in female meiosis, with a particular emphasis on studies in humans. the stage of cell division when the spindle segregates chromosomes by pulling them to opposite spindle poles. a stage in early embryo development that forms before implantation into the uterus. the region of a chromosome where the kinetochore is assembled and microtubules attach. an event specific to meiosis where DNA of homologous chromosomes is covalently exchanged to produce chromosomes with new allele combinations and that links homologous chromosomes with each other to form a bivalent. a proteinaceous structure assembled on the centromeres of chromosomes that binds spindle microtubules responsible for pulling chromosomes apart during segregation. a single kinetochore incorrectly bound to microtubules originating from opposite spindle poles. the stage of cell division when spindle microtubules align chromosomes at the metaphase plate between spindle poles before anaphase. a female germ cell that becomes a fertilizable egg after meiosis. the product of asymmetric cell division during female meiosis containing discarded genetic material from the oocyte. a chromosome segregation error where cohesion between sister chromatids is lost, permitting them to randomly segregate during meiosis. two identical copies of a chromosome replicated during the S phase of the cell cycle. a male germ cell produced by meiosis that can fertilize an oocyte. a cytoskeletal network comprising microtubules formed between two spindle poles that segregates chromosomes during cell division. a type of chromosome comprising a pair of sister chromatids that forms abnormally in meiosis I. Univalents can form by the premature splitting of a bivalent before anaphase I, or if chromosomes fail to undergo homologous recombination.