Gametic mitochondrial DNA
One of my recent reads was about the mitochondria in the oocyte. The mitochondria is more than merely just the boring sentence “power house of a cell”. I mean, it is what it is but, there is more insight that goes into the phrase.
It is known that mitochondria is of paramount importance with regard to the cell’s respiratory activities. However, what I did not know was that the mitochondrial DNA content is highly variable. In this, I talk mainly about the mitochondrial DNA content in oocyte aka the female gamete.
Briefly, the oocyte develops from the primordial germ cell. Around the 5th week of gestation, these primordial germ cells migrate to the future gonads and begin proliferating to produce oogonia (surrounded by follicular cells) which then develops into the primary oocyte which is arrested at prophase 1 of meiosis 1. This happens during the fetal life. At birth, there are approximately 2 million primary oocyte which readily undergo atresia or death until menopause. at menarche, the primary oocytes surrounded by follicular cells slowly start growing due to hormonal stimulus and among the few (5-12) follicles that are growing, one follicle becomes the dominant follicle and is selected for release by the process of ovulation with response to the LH surge. This leads to the resumption meiosis and are the oocyte (now, called secondary oocyte) is again arrested at metaphase II of meiosis II. At fertilization, the oocyte completes meiosis II and is now called the zygote.
As oogenesis takes place since the fetal life, simultaneously there are a lot of cytoplasmic changes taking place within the cell as well. Recent research suggests that the cytoplasmic component (mitochondria) has a central role to play in regulation and normality of early human development.
In oocyte as well as the embryo, the knowledge of mitochondrial parameter such as the mitochondrial DNA (mtDNA) copy number has been related to the lower pregnancy rates and aneuploid births. Therefore, mtDNA content can act as a marker or a reflection of the maturity of oocyte.
mtDNA content in oocyte are highly variable. that is, there is an increase and decrease in the mtDNA content at different stages of the oocyte development since the time of primordial germ cell proliferation until after the zygote development into a blastocyst and further. The fluctuation maybe as a reason for the constant change in energy demand throughout the various developmental stages. There is seen an upregulation mtDNA content at the preovulatory stage. The reason for which is explained as the signals received from the rise in LH that causes preovulatory oocyte to undergo final maturation before ovulation. Low mtDNA copy numbers have been associated with maturation and fertilization failure of oocytes and poor embryo performance in vitro. However studies suggest that almost 80% of the mtDNA detected in a mature oocyte are not measurable in the cleavage stage embryo. And again, post implantation, there is seen an increase in mtDNA content. This is explained as a reason for differential energy demands during preovulatory and early embryonic stages.
The differential energy demand is not the only reason for the fluctuation of mtDNA copy numbers. The upregulation of mtDNA is also considered as a compensatory mechanism to increase ATP production under conditions of reduced respiratory function and also to compensate for bioenergetic deficiencies associated with sublethal mitochondrial dysfunction may be particularly relevant for women of advanced reproductive age. As maternal age increases there occurs mutations in the mtDNA and thereby affecting the maturation of the oocytes in such women. However, the mtDNA compensatory mechanism in such women have yet to be confirmed.