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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.
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.
Epigenetics of anxiety and stress–related disorders is the field studying the relationship between epigenetic modifications of genes and anxiety and stress-related disorders, including mental health disorders such as generalized anxiety disorder (GAD), post-traumatic stress disorder, obsessive-compulsive disorder (OCD), and more.
In one theory, meiosis is primarily an adaptation for repairing DNA damage. Environmental stresses often lead to oxidative stress within the cell, which is well known to cause DNA damage through the production of reactive forms of oxygen, known as reactive oxygen species (ROS). DNA damages, if not repaired, can kill a cell by blocking DNA ...
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]
Arrested oocytes do not enter the subsequent stage, anaphase I. DNA double strand breaks, UVB and ionizing radiation induced DNA damage cause an effective block to anaphase promoting complex activity. [57] This checkpoint may help prevent oocytes with damaged DNA from progressing to become fertilizable mature eggs. [57]
The integrated stress response can be triggered within a cell due to either extrinsic or intrinsic conditions. Extrinsic factors include hypoxia, amino acid deprivation, glucose deprivation, viral infection and presence of oxidants. The main intrinsic factor is endoplasmic reticulum stress due to the accumulation of unfolded proteins.
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 .