In Situ Gene Therapy Rescues Doxorubicin-induced Ovarian Damage via Adenovirus Mediated Sirt1 and Tgfbr2

Chemotherapy-induced ovarian damage and fertility loss have negative impacts on the quality of life for female cancer patients worldwide. Thus, we aimed to explore the feasibility and safety of gene therapy for prevention of such damage. First, we validated doxorubicin-induced ovarian damage in human and mouse ovarian tissues and identified two key genes (Sirt1 and Tgfbr2). Next, we generated AdV-Sirt1 and AdV-Tgfbr2 after vectors screening (AdV,AAV and LV) for their ability to transduce mouse ovaries. Finally, we conducted in situ ovarian injection of AdV-Sirt1 and AdV-Tgfbr2 in doxorubicin-treated mice and assessed their ovarian functions and reserves. The interventions dramatically alleviated doxorubicin-induced ovarian damage without apparently influencing the health status of their offspring. Together, our results indicate that AdV-Sirt1 and AdV-Tgfbr2 can serve as effective and safe agents for reducing doxorubicin-induced ovarian damage and also suggest that they may be potentially applicable for post-chemotherapy protection in female cancer patients.