Report
Teaser, summary, work performed and final results
Periodic Reporting for period 3 - GermAge (The aging germ cell – biological pathways, risk factors and mechanisms underlying anincreasing medical and socio-economic problem)
Teaser
The goal of GermAge is to obtain critical insights into the devastating decline in germ cell quality during aging, and thus to define the determinants, pathways and risk factors for age-dependent infertility, aneuploidy and inherited diseases. The increasingly aging population...
Summary
The goal of GermAge is to obtain critical insights into the devastating decline in germ cell quality during aging, and thus to define the determinants, pathways and risk factors for age-dependent infertility, aneuploidy and inherited diseases. The increasingly aging population and the strongly increasing age of parenthood are associated with very serious medical problems and thus severe consequences for the health systems and socio-economic welfare of our societies. Therefore it is imperative to understand the biological basis and risk factors of the steep age-dependent decline in female and male germ cell quality. In addition to advancing progress in our understanding the biology of germ cell aging, the expected results will provide insights into the feasibility of intervention strategies designed to reduce the impact of ageing on reproductive health, and on the genetic risk to children of older parents. Our work will also lead to improved diagnostics in reproductive technologies including quality control in cryo-storage of male and female germ cells for the purpose of fertility preservation, diagnosis of risk of inherited diseases including aneuploidy in carriers of specific mutations, and prognosis based on individualized genomics on age-related quality decline of oocytes and spermatozoa. GermAge will also raise public awareness of the risks associated with postponing parenthood.
Work performed
The work performed by GermAge during the initial project period has established key preconditions for addressing the overall questions outlined above. A number of important technologies were established such as sophisticated live cell imaging of oocytes. Several new transgenic mouse strains were generated which allow visualization and manipulation of factors critical in age-dependent decline of germ cell quality like cohesin proteins, and a series of new reagents was developed and tested that are instrumental for further experiments such as specific antibodies and a specific marker for critical chromosome regions like the pericentromeric. Cohesins form protein complexes, which are essential to hold chromosomes together in a properly ordered structure so that the cell is able to correctly divide them during cell division and provide each daughter cell with the correct number and kind of chromosomes. Earlier members of GermAge showed that in ageing oocytes cohesins decay results in aneuploidies possibly causing diseases such as trisomy 21. Recently, the analysis of proteins that control cohesin behavior was initiated and yielded first new insights. Studies of ageing male germ cells including the germ stem cells from which sperm develops have also been started
Final results
Initial results already demonstrate the importance of certain proteins such as cohesin regulators in maintaining proper chromosome architecture and germ cell survival. Further data demonstrate the localization of cohesins on germ cell chromosomes, which is important for understanding the particular role of proteins such as cohesins in the maintenance of genome integrity and thus in avoiding chromosome missegregation. Reports on the new findings were delivered at various national and international meetings.
Website & more info
More info: http://www.germage.eu.