Duration: 24 months
Long-term space missions present important issues for the human health, primarily because of the exposure to significant environmental stressors such as cosmic radiation, pressure variations, and microgravity [1]. In particular, permanence in prolonged microgravity aboard, for example, the International Space Station (ISS), has severe effects on human physiology including reductions in bone and muscle mass, alterations in brain structure, and changes in the distribution of intravascular fluids [2]. Considering the reproductive system, space flights have a notable impact on female health, causing changes in menstrual cycles, hormonal fluctuations, radiation exposure of oocytes, and variations in blood flow within the ovaries [3]. Recent studies have highlighted the critical role of ovarian follicles for oocyte quality by providing physiological support, nutrition, and signaling for maturation [4, 5]. Variations in follicle components, primarily composed of granulosa and theca cells, lead to cytoskeletal reorganization and hormonal changes to adapt to the environment. Ethical considerations and scarcity of research samples have limited the availability of data in the literature, hindering significant advancements in the field. Here, we aim to develop ovarian follicles within an organ-on-chip systems; this model will allow exposition to simulated microgravity using a random positioning machine (RPM). After comprehensive analysis through cellular, molecular, and omic techniques, we will leverage machine learning to predict potential drug compounds to address the identified issues. The in-silico approach will allow to analyse extensive datasets of known physicochemical features to select molecules for testing, minimizing the risk of unforeseen toxicities during oogenesis. This multidisciplinary project offers novel approaches to address microgravity-related risks to the female reproductive system, with potential spill-over for mitigating similar abnormalities on Earth.
