Sex differences in preclinical models of sepsis: a systematic review

Many differences exist between men and women when it comes to how diseases affect the body, and how effective treatments for those disease are. Despite this, medical research has demonstrated a lack of gender diversity over the years, even more so in the preclinical animal research setting. Significant evidence exists demonstrating a large portion of animal research is performed only in male animals. In the past, drugs have been approved by regulatory agencies, only to later be taken off the market due to detrimental effects in women. These harms could have potentially been avoided, had the preclinical research been sufficiently performed in both male and female animals. Our team wishes to study differences in treatment effect between sexes in animal models of sepsis . We will identify these potential differences by reviewing the current scientific literature, in order to identify existing research pertaining to sex-dependent responses to treatment in this devastating disease. Sepsis has been chosen as differences in outcomes have been seen between sexes in the human population, and understanding those differences in animal research may lead to more efficient discovery of treatments. Results from this study will also contribute to a nation-wide initiative, as members of our team are currently in the process of developing Canadian network of preclinical sepsis researchers who will conduct experiments together. Elements of biological sex will feature prominently in these experiments, and our review study proposed here will be essential to appropriately plan these experiments. Ultimately, by identifying differences in treatment response between sexes in preclinical studies, we can better identify therapies and drugs to bring to clinical trials in humans.