Modeling female reproductive disturbances post-traumatic injury in Drosophila melanogaster
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Citation
Abstract
Traumatic injuries (TIs) from intimate partner violence, vehicular collisions, high-impact sports, and even mundane activities can be fatal. However, survivors of TIs can have residual pathophysiological disturbances post-injury that lead to life altering conditions, including neurodegenerative diseases, mental illness, and metabolic disorders. Reproductive issues are a known consequence of TI especially in women, however this has remained poorly understood. These issues with reproduction are seen through menstrual cycle dysregulation, lower libido, decreased fertility, and increased rates of miscarriages. These consequences are not only localized to the time of injury but can persist through the remainder of the individual’s life.Drosophila melanogaster have recently emerged as a stellar model of TI due to the conservation of molecular/cellular cascades following injury response, relatively short lifespans, and the avoidance of many of the ethical dilemmas of using vertebrate models. Reproductive consequences had not previously been tested using the Drosophila model, and we have found that reproductive consequences are conserved. These reproductive consequences come in the form of decreased egg laying behavior, increased cell death and the retention of mature egg chambers, mimicking issues in ovulation. To investigate the genetic and cellular mechanisms of these reproductive responses, we hypothesized that either hormonal or immune disruption following TI leads to these changes. Interestingly, patients who have undergone TI have higher rates of diabetes and immune dysregulation, supporting that reproductive deficits may be linked to hormonal and/or immune breakdown. We investigated potential roles of the major hormones insulin-like peptide 8 (Ilp8), neuropeptide F (NPF), and adipokinetic hormone (AKH) via knockdowns in several tissues and while we did not recapitulate findings with Ilp8 and NPF we did however see recapitulation of retention with the knockdown of akh. Additionally, we found that disruption to the major phagocytic receptor of Drosophila, Draper (drpr), leads to similar defects in reproduction. These findings suggest that immune dysregulation contributes to these reproductive failures post-TI.
Description
2025
License
Attribution 4.0 International