b'6 Carnegie Science|Fall 2020Jumping Genes and Egg-Cell Quality Affect Fertility and HealthJUMPING GENES ACTIVE JUMPING GENES EVADEDThis image displays the dramatic increase in the endowment of immature egg cells in newborn mice when fetal oocyte attrition is prevented from occurring. White shows an ovary exposed to normal physiological activity of the jumping gene LINE-1. Purple is an ovary thats 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 labeled by a germ cell-specific marker. Image courtesy Marla Tharp and Navid Marvi, Carnegie Institution for ScienceNew work from Carnegies Marla Tharp, Safia Malki, and Alex Bortvin reveals a mechanism by which, even before birth, the body tries to eliminate poor-quality egg cells. Naturepublished the findings. CommunicationsSome organisms produce a large number of offspring, many of which dont survive to adulthood. Females in these species continually produce new egg cells throughout their reproductive lives, Bortvin explained. But in mammals, females are born with a fixed supply of eggs and produce few progeny. Thus, each egg is a precious commodity necessitating quality control to ensure theMarla Tharp (left) was lead author on the paper. She represented the lab with Alex Bortvin well-being of her children. (right) at the inaugural March for Science in Washington, D.C., in 2017 shown here. For 50 years, scientists have known that up to 80% of aImage courtesy Alex Bortvins lab, Carnegie Institution for Sciencefemale mammals original pool of potential egg cells is eliminated during fetal development through a process calleddrug that blocks the multiplication of HIV and LINE-1, temporarily fetal oocyte attrition (FOA). This phenomenon is in all studiedprevented death of immature egg cells. This observation mammals. Despite its ancient origins, much about this processindicated that that there was more than one mechanism to remains mysterious. Bortvin and his team say FOA targetsdetect and eliminate egg cells with excessive LINE-1 activity.reduced-quality egg cells.Taking this idea to the next stage, the research team expanded Previous work by Bortvin and Malki indicated that thistheir investigations by using AZT in mice lacking a protein called elimination of potential egg cells during fetal development is relatedChk2, which detects DNA damage and either repairs it or flags the to a transposable element, or jumping gene, called LINE-1.DNA-damaged cells for death. When the LINE-1 jumping gene was Originally discovered by Carnegie biologist Barbarainhibited by AZT, and the Chk2 protein was rendered ineffective by McClintock, jumping genes can move around in a cells DNA,mutation, the reserve of egg cells increased. often breaking genes but sometimes also introducing geneticWhats more, the shutting off the fetal egg cell elimination innovations that improve a species survival.process did not decrease fertility, Tharp explained. This provides Bortvins group had previously demonstrated that jumpingfurther evidence that this is a quality control process undertaken genes are quashed during sperm production, but not during eggto try to maintain the caliber of the available egg supply.development. They theorized that purging the cells with theMore work is needed to determine whether these findings greatest activity by the jumping gene LINE-1 allows for thecould help combat infertility selective survival of the immature eggs that are less likely todue to premature ovarian SUPPORT:succumb to jumping genes.failure by increasing aThe National Institutes of Health funded this work.Indeed, Malki and Bortvin previously discovered that AZT, awomans total egg supply.'