The repx-2 Gene Regulates Reproductive Aging in Caenorhabditis elegans

Abstract

One of the earliest human aging phenotypes is the decline in female reproductive capacity, and as more women opt to give birth later in life, this natural decline becomes an issue. Reproductive decline begins long before the onset of menopause and is therefore thought to be the result of declining oocyte quality rather than quantity. In C. elegans, oocyte quality is maintained via three known genetic pathways. However, much is still unknown about these pathways, and the Murphy lab hypothesizes that undiscovered pathways and regulators exist. A previous graduate student in the Murphy lab carried out a pilot Mos1 transposon-mediated forward genetic screen to identify novel reproductive aging regulators, and seven untested candidate mutant lines from this screen were investigated in the current study. We found that two of these lines showed extended self-reproductive spans, and one of them had its Mos1 insertion between Y47G6A.14 and spg-7. Follow-up RNAi studies determined that Y47G6A.14 regulates reproductive aging, and the gene was renamed repx-2. Finally, we found that downregulation of repx-2 significantly extends mated reproductive span, and transcriptomic data suggested that repx-2 acts in the germline to regulate reproductive aging. Taken together, our findings expand on our knowledge of the genetic regulators of reproductive aging, which will be critical in the development of new modes of intervention in human maternal age-related reproductive decline.