Understanding Epigenetic Mechanisms Associated with Heritable Fertility Trends in D. Melanogaster

Overview

The global rate of infertility stands at an all-time high and nutrition has been discussed as an impactful factor in such skewed trends. Stable oogenesis is continually threatened by genotoxic stress stemming from DNA damage, much of which is inflicted by transposition at the germline. Using Drosophila melanogaster as a biological model, this study successfully identified multiple heritable mechanisms that govern nutritionally malleable response to DNA damage and infertility at the molecular level, including piRNA and, downstream, checkpoint kinases such as ATR, CHK1, and CHK2. Imaging analysis software ImageJ and Icy were used to quantify pole plasm deposits and intermediate stage proliferation in subjects. Next-generation sequencing (NGS) was used to holistically profile the cellular transcriptome of wild-type and mutant D. melanogaster, uniquely elucidating the role of kinase-mediated DNA damage response pathways in the context of genotoxic insults and further identifying the PIWI-interacting RNA (piRNA) pathway, a mammalian homologue, as a safeguard against genomic instability in response to variable dietary intake. This study also identified MT-ND3, MT-ND4, and MT-ND5 as potentially impactful genes in piRNA localization. Presented herein is a model for further experimental analysis of the heritable properties of DNA damage repression that could be used in the development of methods to address underlying intrinsic mutations fueling the burgeoning fertility crisis.