Is Sexually Dimorphic Adaptation to Oxidative Stress a Tissue Specific or a Systemic Phenomenon in D. Melanogaster

Sex-specific differences are evident from fruit flies to humans. The ability to activate stress-responsive genes is sex and oxidant-dependent, with earlier work demonstrating adaption in D. melanogaster to hydrogen peroxide (H 2 O 2 ) occurring in a female-specific manner. We have previously shown that whole-body overexpression of the transformer female-specific transcript ( traf ) led to the successful generation of pseudo-female fruit flies, which are chromosomally male, but phenotypically female, and increased ability to adapt to H 2 O 2 . In this study, we sought to investigate if a specific tissue is necessary for adaptation to H 2 O 2 pretreatment. To investigate this, we feminized individual tissues in male fruit flies: the gut, the nervous system, fat bodies, and oenocytes. Prior work from Regan and colleagues (2016) showed feminized male guts, under caloric restriction, demonstrated increased lifespan, a phenomenon usually selective for females. In the present study, males with specific feminized tissues were either not pretreated or were pretreated with low, signaling doses (µM) of H 2 O 2 before being subjected to a semi-lethal amount of H 2 O 2 . Adaptation was measured by changes in survival. We found that the feminization of the four individual tissues in males did not endow an adaptive response to H 2 O 2 . This finding indicates a potential systemic interaction may be necessary to cause a female-specific response, requiring the feminization of multiple tissues. We consider these studies to be the first steps in (one day) understanding sexually dimorphic oxidative stress responses and adaptive homeostasis in tissues of higher organisms.