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The DNA of a cell is vulnerable to the damaging effect of oxidative free radicals produced as byproducts of cellular metabolism. DNA damage occurring in oocytes, if not repaired, can be lethal and result in reduced fecundity and loss of potential progeny.
Oocyte abnormalities can be caused by a variety of genetic factors affecting different stages in meiosis. [1] Moreover, ageing is associated with oocyte abnormalities since higher maternal age is associated with oocytes with a reduced gene expression of spindle assembly checkpoints which are important in maintaining stability in the genome.
Oxidative stress mechanisms in tissue injury. Free radical toxicity induced by xenobiotics and the subsequent detoxification by cellular enzymes (termination).. Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. [1]
The secondary oocyte continues the second stage of meiosis (meiosis II), and the daughter cells are one ootid and one polar body. Secondary oocytes are the immature ovum shortly after ovulation, to fertilization, where it turns into an ootid. Thus, the time as a secondary oocyte is measured in days.
When there is DNA damage, Mdm2 is phosphorylated, most likely caused by ATM. The phosphorylation of Mdm2 leads to a reduction in the activity of Mdm2, thus preventing the degradation of p53. Normal, undamaged cell, usually has low levels of p53 while cells under stress and DNA damage, will have high levels of p53. [13]
The response of oocytes to DNA double-strand break damage involves a pathway hierarchy in which ATR kinase signals to CHEK2 which then activates p53 and p63 proteins. [ 15 ] In the fruit fly Drosophila , irradiation of germ line cells generates double-strand breaks that result in cell cycle arrest and apoptosis .
This is known as the primary oocyte. Human females are born with all the primary oocytes they will ever have. [10] Starting at puberty the process of meiosis can complete resulting in the secondary oocyte and the first polar body. [10] The secondary oocyte can later be fertilized with the male sperm.
The emergence of Earth's oxygen-rich atmosphere (known as the "oxygen catastrophe") due to photosynthetic organisms, as well as the presence of potentially damaging free radicals in the cell due to oxidative phosphorylation, necessitated the evolution of DNA repair mechanisms that act specifically to counter the types of damage induced by ...