Abstract

BackgroundImproved cancer therapeutics and enhanced cancer survivorship have emphasized the severe long-term side effects of chemotherapy. Specifically, studies have linked many chemotherapy agents with primary ovarian insufficiency, although an exact insult model has not yet been determined. To investigate and ultimately solve this problem, a novel device for extended study of mammalian ovaries in vitro was developed.MethodsA bioreactor was fabricated for bovine ovarian culture that provides intravascular delivery of media to the ovary through isolation and cannulation of a main ovarian artery branch. Whole ovaries were cultured in vitro using three methods: (1) continuously supplied fresh culture media, (2) recirculated culture media, or (3) continuously supplied fresh culture media supplemented with 500 nM doxorubicin for 24 or 48 h. TUNEL assay was used to assess apoptotic cell percentages in the three groups as compared to uncultured baseline ovaries.ResultsThe ovary culture method was shown to maintain cell viability by effectively delivering nutrient-enriched pH-balanced media at a constant flow rate. Lower apoptosis observed in ovaries cultured in continuously supplied fresh culture media illustrates that this culture device and method are the first to sustain whole bovine ovary viability for 48 h. Meanwhile, the increase in the percentage of cell apoptosis with doxorubicin treatment indicates that the device can provide an alternative model for testing chemotherapy and chemoprotection treatments to prevent primary ovarian insufficiency in cancer patients.ConclusionsAn ovarian bioreactor with consistent culture media flow through an ovarian vasculature-assisted approach maintains short-term whole bovine ovary viability.Electronic supplementary materialThe online version of this article (doi:10.1186/s13048-016-0249-4) contains supplementary material, which is available to authorized users.

Highlights

  • Improved cancer therapeutics and enhanced cancer survivorship have emphasized the severe long-term side effects of chemotherapy

  • These factors provide motivation to determine the cellular cause of chemotherapy-induced primary ovarian insufficiency (POI) and develop drug-based measures to inhibit its development in cancer patients

  • Bioreactor system setup and functionality To study the bioreactor system functionality and efficacy, we examined fluid distribution through the ovarian tissue over time

Read more

Summary

Introduction

Improved cancer therapeutics and enhanced cancer survivorship have emphasized the severe long-term side effects of chemotherapy. Studies have linked many chemotherapy agents with primary ovarian insufficiency, an exact insult model has not yet been determined. While innovations in cancer chemotherapy allow patients to live longer, they have been shown to lead to subsequent long-term complications, such as primary ovarian insufficiency (POI) [1]. Further complications have been associated with POI, including onset of osteoporosis and cardiovascular disease [2, 3]. These factors provide motivation to determine the cellular cause of chemotherapy-induced POI and develop drug-based measures to inhibit its development in cancer patients. The effects of DXR have been documented in mice as well as marmoset ovaries including DNA damage within 2 h, follicular attrition in as little as 12 h postinjection, and permanent reduction in ovary size up to Zanotelli et al Journal of Ovarian Research (2016) 9:47

Methods
Results
Discussion
Conclusion
Full Text
Paper version not known

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.