The Detection of Early Epigenetic Inheritance of Mitochondrial Stress in C. Elegans with a Microfluidic Phenotyping Platform

Fluctuations and deterioration in environmental conditions potentially have a phenotypic impact that extends over generations. Transgenerational epigenetics is the defined term for such intergenerational transient inheritance without an alteration in the DNA sequence. The model organism Caenorhabditis elegans is exceptionally valuable to address transgenerational epigenetics due to its short lifespan, well-mapped genome and hermaphrodite behavior. While the majority of the transgenerational epigenetics on the nematodes focuses on generations-wide heritage, short-term and in-depth analysis of this phenomenon in a well-controlled manner has been lacking. Here, we present a novel microfluidic platform to observe mother-to-progeny heritable transmission in C. elegans at high imaging resolution, under significant automation, and enabling parallelized studies. After approximately 24 hours of culture of L4 larvae under various concentrations and application periods of doxycycline, we investigated if mitochondrial stress was transferred from the mother nematodes to the early progenies. Automated and custom phenotyping algorithms revealed that a minimum doxycycline concentration of 30 µg/mL and a drug exposure time of 15 hours applied to the mothers could induce mitochondrial stress in first embryo progenies indeed, while this inheritance was not clearly observed later in L1 progenies. We believe that our new device could find further usage in transgenerational epigenetic studies modeled on C. elegans.