The Adverse Outcome Pathway to Deposition of Energy Leading to Female Decreased Fertility

Deposition on energy to infertility

Evgeniia Kazymova

<p>Jessica D'Urbano, Awurakua Asamoah-Mensah, Saadia Khilji, Shiven Gupta, Amy Michelle Simms, Biyanka Hati, Vinita Chauhan</p> <p>Jean Calleja Agius, Edouard Azzam, Ruth Farrell, Begum Aydogan Mathyk, Haley Race, Aylin Yaba Ucar, Marcelo Vasquez</p> <div> <div> <div> </div> <div> <div> <div> </div> <div> <p dir="auto"> </p> <p dir="auto"> </p> </div> </div> </div> </div> </div>

2.7

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:"Times New Roman",serif"><span style="font-family:"Lato",sans-serif">Infertility is a disorder of the reproductive system defined by the inability to conceive after 12 months of regular, unprotected intercourse. Ionizing radiation is known to exert gonadotoxic effects, impacting female fertility by damaging reproductive organs or disrupting the hypothalamic-pituitary-gonadal axis. These effects can lead to ovarian insufficiency, pubertal arrest, and infertility, with severity depending on radiation dose and the individual's age. As space missions extend in duration and distance, understanding the effects of space radiation on female fertility becomes increasingly critical, not only for the individual but also for potential impacts on future generations. </span></span></span><span style="font-size:11pt"><span style="font-family:"Times New Roman",serif"><span style="font-family:"Lato",sans-serif">To address this need, International Space Agencies, in collaboration with Health Canada and the Nuclear Energy Agency, are developing an Adverse Outcome Pathway (AOP) to consolidate knowledge on radiation-induced infertility in females. This initiative complements existing AOPs addressing space-related health risks such as cataracts, vascular remodelling, bone loss, and cognitive impairments. The proposed AOP uses scoping review methodology combined with expert consultation to identify the limited but growing literature, drawing from invitro studies, animal models and past spaceflight missions.</span></span></span><span style="font-size:11pt"><span style="font-family:"Times New Roman",serif"><span style="font-family:"Lato",sans-serif">The hypothetical AOP links deposition of energy as the molecular initiating event (MIE) to a series of measurable key events (KEs) including oxidative stress, DNA damage, oocyte apoptosis, and reduced follicular pool ultimately leading to infertility. These events align with AOPs 238, 311, and 396 in the AOP-Wiki (www.aopwiki.org). </span></span></span><span style="font-size:11pt"><span style="font-family:"Times New Roman",serif"><span style="font-family:"Lato",sans-serif">The resulting AOP can inform risk assessment, identify biomarkers, guide countermeasure development, and support multi-stressor risk evaluations. Its broader applicability may also enhance our understanding of infertility caused by chemical exposures, providing a valuable tool for space medicine and environmental toxicology.</span></span></span></p>

<div> <table class="table table-bordered table-fullwidth"> <thead> <tr> <th>Modulating Factor (MF)</th> <th>Influence or Outcome</th> <th>KER(s) involved</th> </tr> </thead> <tbody> <tr> <td> </td> <td> </td> <td> </td> </tr> </tbody> </table> </div>

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2026-06-26T16:12:16