The Cell Cycle, Cellular Growth, and Cancer
Health and The Cell Cycle, Cellular Growth, and Cancer
It is been blamed for the split of Sheryl Crow and Lance Armstrong. Some people call it their biological clock, and for many women in their 30s and 40s, its ticking can be more than a little bit loud. Money doesn't solve everything, and even for women with deep pocketbooks, like Hollywood stars, having a child later in life can be difficult.
While you probably have heard about a woman's biological clock in reference to the difficulty in having children later in life, you may not understand exactly what it needs to do with cell division. A large player in age related pregnancy difficulties is aneuploidy, a condition where a cell has extra (or missing) copies of a particular chromosome. For women late in their reproductive lives, the possibility of their releasing an aneuploid egg can be 50% or higher. In fact, while the percentage of clinically recognized pregnancies containing an abnormal number of chromosomes is about 2-3% for women in their 20's, the percentage jumps to 30-45% for women in their 40's (Hunt & Hassold, 2008). Aneuploidy is the leading cause of miscarriages, although aneuploidy of some chromosomes is compatible with life. A good example is having an extra copy of all or part of chromosome 21, which leads to Down Syndrome.
How does aneuploidy happen? Well, we know that most trisomies occur during oogenesis, or the production of a female's eggs, most commonly in meiosis I. We also know that the occurrence of aneuploidy increases with the age of the mother. Why the age correlation? One amazing thing about human meiosis is that the first meiotic division occurs in the fetal ovary, but doesn't finish until ovulation, which can be anywhere from 10-50 years later. While this delay may help explain the age correlation with aneuploidy, it is not the only answer. For example, a surprising number of chromosome 18 trisomies are due to chromosome missegregation in meiosis II, and women who have just started puberty also have a surprisingly high rate of producing aneuploid eggs (Hassold, Hall, & Hunt 2007).
What could be going wrong in meiosis I that could result in aneuploidy? If you remember back to our In Depth section, homologous chromosomes are held together in meiosis I by the linkages generated through recombination. A common theme concerning trisomy 21 cases is that the pattern of recombination is altered. If recombination were to fail completely, this would be expected to produce completely random segregation of that chromosome at meiosis I. In other words, there would be a 50% chance that a daughter cell would have an extra copy of the chromosome, and a 50% chance that the cell would be missing that chromosome all together. Current scientific research has also found that mutations in the proteins important for gluing the sister chromatids together and ensuring the pairing of homologous chromosomes—both major events of prophase I—can also lead to chromosome segregation defects (Hassold, Hall, & Hunt 2007).
Even as scientists make significant strides in understanding what goes wrong in meiotic cell division, any clinical solutions to delay or eliminate age related nondisjunction are far off. For many American women, this is disconcerting, especially given the trend that over the last 30 years women have delayed their first pregnancy by about 3.6 years (Hunt & Hassold, 2008). To compound the issue, some recent research has suggested that environmental factors may also increase the amount of maternal nondisjunction. You may have heard about BPA (bisphenol A) that, after being linked to aneuploidy in model organisms, has been increasingly removed from baby products and water bottles. It brings up the somewhat unfortunate possibility that the female reproductive system is not only captive to its own biological clock, but also to environmental factors.