Increased Parental Age Compromises Primordial Germ Cell Migration to the Gonad

Increased Parental Age Compromises Primordial Germ Cell Migration to the Gonad

Lacy J Barton¹, Rosario Lopez-Roca Fernandez¹; Harry Siegel¹, 

¹Dept of Neuroscience, Developmental and Regenerative Biology, The University of Texas at San Antonio

 

Abstract Text:

Increased parental age compromises gamete quality and increases risk of developmental disorders in offspring. The degree to which increased parental age compromises germline development in offspring is less clear. Using Drosophila melanogaster, we found that even minor increases in parental age compromise an essential step in germ cell development: the migration of primordial germ cells (PGCs) to the embryonic gonad. To measure the extent of this phenomenon, we intercrossed three wild type Drosophila strains and quantified the number of mis-migrated PGCs in 120 embryos from matched parents at five different ages. Across all wild type backgrounds tested, we found a consistent, sharp, and statistically significant increase in PGC migration errors between parental ages six and nine-days old, such that more than half of embryos from nine-day old parents exhibited mild, moderate, or severe PGC migration defects. Only ~15% through their normal lifespan, nine days old is much younger than previously reported ages when DNA damage and chromosomal segregation errors increase in Drosophila gametes. To test whether increased errors in PGC migration coincide with accumulation of DNA damage in gametes, we quantified gammaH2Av foci in oocyte and sperm nuclei at all five parental ages. We found increased errors in PGC migration occurred in the absence of any detectable DNA damage in parental oocytes and sperm. We are currently testing the role of age-dependent hormone dynamics in flies and the impact of parental age on PGC migration in mice. In humans, errors in PGC migration risk the development of extragonadal germ cell tumors. Our Drosophila-based findings are consistent with epidemiological studies positively correlating parental age with germ cell tumor incidence. Together, these findings suggest that minor increases in parental age have the potential to impact two subsequent generations and reinforce the need for embryonic germ cell biologists to precisely control for parental age.