Follicular Atresia and Mitochondria - Is this how the ovary picks the best egg with the best mitochondria?
I wrote previously about how babies are born young. The essence is that for youth you need efficient mitochondria with a high membrane potential (when running in a steady state generating ATP). When an egg is created it is created with a mitochondrial bottleneck. This reduces the variation in mitochondrial DNA (mtDNA) to about 3 copies (according to recent research). However, this does not as far as research indicates select for better mtDNA (and hence more efficient mitochondria).
Relatively few babies are born with mitochondrial disease because the eggs don't get fertilised, don't start replicating, don't implant into the uterine wall or miscarry. This is not the only reason for non-viability, but it is a reason. This is seen in how older eggs tend to be less viable. However, there is another selection process for eggs which is called "Follicular Atresia".
Follicular Atresia is a really interesting process and the Wikipedia article that I link to does not explain it properly.
The ovary generates follicles. Each follicle actually has only one egg in it and this is a haploid cell (meaning it has only one set of chromosomes), but it is surrounded by a number of other cells called Granulosa cells. Those cells combined with the egg cell make the follicle.
In each menstrual cycle a number of follicles start developing, but a limited number are selected by the ovary (in humans normally one). The physiology of follicle selection is a free to air review that goes into the details of follicle selection. In short, however, as a response to FSH (follicle-stimulating hormone) a group of follicles start developing (normally 10-20 at this stage). These then start developing, but only one is selected (normally in humans) and the rest undergo "atresia" where the cells undergo atoptosis. What is interesting about this is that the process involves signalling molecules from the egg itself which is signalling to the granulosa cells in the follicle. These are called Oocyte-Secreted Factors. These factors are subject to splicing variants and splicing variants arise from mitochondrial efficiency levels (through the acetylation of splicing factors).
To me that is a logical explanation as to how Follicular Atresia results from inefficient mitochondria and is used to pick the best egg to go for potential fertilisation. However, as yet I have not managed to find a paper to substantiate the step between splicing, Oocyte-secreted factors and atresia. I have found papers that reference splicing and OSFs, but not that make the direct link to atresia. It may be that this is a good research project. From a macro perspective it seems an obvious mechanism, but that is not proof.
I will continue searching for papers on this topic and update this if and when I find relevant papers. I am not aware of an animal with an ovarian based reproductive system in which this process does not occur. Hence to me it seems a conserved mechanism for maintaining mitochondrial quality in the young.
These are some links to papers that may come close on this. I have not yet had the time to read them.
Oocyte transcriptomes and follicular fluid proteomics of ovine atretic follicles reveal the underlying mechanisms of oocyte degeneration
Predictive modeling of oocyte maternal mRNA features for five mammalian species reveals potential shared and species-restricted regulators during maturation
Identification and characterization of canine growth differentiation factor-9 and its splicing variant
Homozygous Splice Site Mutation in ZP1 Causes Familial Oocyte Maturation Defect
Relatively few babies are born with mitochondrial disease because the eggs don't get fertilised, don't start replicating, don't implant into the uterine wall or miscarry. This is not the only reason for non-viability, but it is a reason. This is seen in how older eggs tend to be less viable. However, there is another selection process for eggs which is called "Follicular Atresia".
Follicular Atresia is a really interesting process and the Wikipedia article that I link to does not explain it properly.
The ovary generates follicles. Each follicle actually has only one egg in it and this is a haploid cell (meaning it has only one set of chromosomes), but it is surrounded by a number of other cells called Granulosa cells. Those cells combined with the egg cell make the follicle.
In each menstrual cycle a number of follicles start developing, but a limited number are selected by the ovary (in humans normally one). The physiology of follicle selection is a free to air review that goes into the details of follicle selection. In short, however, as a response to FSH (follicle-stimulating hormone) a group of follicles start developing (normally 10-20 at this stage). These then start developing, but only one is selected (normally in humans) and the rest undergo "atresia" where the cells undergo atoptosis. What is interesting about this is that the process involves signalling molecules from the egg itself which is signalling to the granulosa cells in the follicle. These are called Oocyte-Secreted Factors. These factors are subject to splicing variants and splicing variants arise from mitochondrial efficiency levels (through the acetylation of splicing factors).
To me that is a logical explanation as to how Follicular Atresia results from inefficient mitochondria and is used to pick the best egg to go for potential fertilisation. However, as yet I have not managed to find a paper to substantiate the step between splicing, Oocyte-secreted factors and atresia. I have found papers that reference splicing and OSFs, but not that make the direct link to atresia. It may be that this is a good research project. From a macro perspective it seems an obvious mechanism, but that is not proof.
I will continue searching for papers on this topic and update this if and when I find relevant papers. I am not aware of an animal with an ovarian based reproductive system in which this process does not occur. Hence to me it seems a conserved mechanism for maintaining mitochondrial quality in the young.
These are some links to papers that may come close on this. I have not yet had the time to read them.
Oocyte transcriptomes and follicular fluid proteomics of ovine atretic follicles reveal the underlying mechanisms of oocyte degeneration
Predictive modeling of oocyte maternal mRNA features for five mammalian species reveals potential shared and species-restricted regulators during maturation
Identification and characterization of canine growth differentiation factor-9 and its splicing variant
Homozygous Splice Site Mutation in ZP1 Causes Familial Oocyte Maturation Defect
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