Poor Quality Egg Cells are Threatened by Jumping Genes
This image displays the dramatic increase in the endowment of immature egg cells in new-born mice when the Fetal Oocyte Attrition is prevented from occurring. Shown in white is an ovary exposed to normal physiological activity of the jumping gene LINE-1. Shown in purple is an ovary that’s been treated with AZT to inhibit LINE-1 and mutated to turn off the DNA damage checkpoint Chk2. The nuclei of individual immature egg cells are labelled by a germ cell-specific marker. CREDIT: Marla Tharp and Navid Marvi
Researchers at Carnegie Institution for Science, USA have discovered a mechanism in which the body tries to eliminate egg cells of the poorest quality. Published in Nature Communications, the findings indicate that this elimination during foetal development is related to a transposable element, or “jumping gene”, called LINE-1 that promotes the survival of eggs with more “jumping gene” activity.
It’s widely known that a woman’s supply of eggs is finite and needs to maintain a good quality of genetic material. Up to 80% of a female mammal’s original pool of potential egg cells are eliminated during foetal development through a process called foetal oocyte attrition (FOA). The mechanisms behind this process are unknown, although it’s conserved in all studied mammals to date. The new research says that FOA targets those egg cells with reduced genetic quality.
The team found that a transposable element, or “jumping gene”, called LINE-1 could be related to the elimination of certain egg cells in foetal development. Jumping genes can “jump” to different parts of DNA, which can introduce new genetic innovations that improve a species’ survival, but can also break genes.
Jumping genes don’t play a role in sperm production like they do during egg development. The team theorised that by removing eggs with the highest activity of the jumping LINE-1 gene, other immature eggs with low jumping LINE-1 activity could survive.
They found that a drug called AZT blocked the multiplication of HIV and LINE-1, and temporarily prevented death of immature egg cells. It showed that there’s more than one mechanism to detect and eliminate egg cells with excessive LINE-1 activity.
In the next stage of their research, they used AZT in mice lacking Chk2, a protein that can detect DNA damage. When the LINE-1 jumping gene was inhibited by AZT and no Chk2 was present, the reserve of egg cells increased. This means that egg cells with lower quality of DNA could survive and were not removed during FOA.
Jumping genes could play a part in the quality control process to maintain a good quality of the available egg supply. More work is needed to see if this mechanism plays a role in premature ovarian failure and could help combat this infertility by increasing a woman’s total egg supply.