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Antioxidants induce apoptosis of rat ovarian theca-interstitial cells
Izabela J Rzepczynska1, Nastaran Foyouzi, Piotr C Piotrowski
1Department of Gynecology and Obstetrics, Poznan University of Medical Sciences, Poznan, Poland.
Abstract:
Regulation of growth of ovarian theca-interstitial tissues is essential for normal ovarian development and function. Reactive oxygen species are involved in modulation of signal transduction pathways, including regulation of tissue growth and apoptosis. Previously, we have demonstrated that antioxidants inhibit proliferation of theca-interstitial cells. This report evaluates the effects of antioxidants on apoptosis of rat theca-interstitial cells. The cells were cultured in chemically defined media without or with vitamin E succinate and ebselen. Apoptosis was evaluated by cytochemical assessment of nuclear morphology, activity of executioner caspases 3 and 7, and determination of staining with annexin V in combination with propidium iodide. Both tested antioxidants induced significant morphological changes consistent with apoptosis, including chromatin condensation, nuclear shrinkage, and pyknosis. Antioxidants also induced other hallmarks of apoptosis including increased activity of caspases 3/7 as well as increased staining with annexin V. The present findings demonstrate that antioxidants with distinctly different mechanisms of action induce a series of events consistent with the process of apoptosis in ovarian mesenchyme. These observations may be of translational-clinical relevance, providing mechanistic support for the use of antioxidants in the treatment of PCOS, a condition associated with excessive growth and activity of theca-interstitial cells.
Insights
Antioxidants promote apoptosis in rat ovarian cells. This finding supports using antioxidants to treat Polycystic Ovary Syndrome (PCOS), which involves excessive theca-interstitial cell growth.
Area of Science:
- Reproductive biology
- Cellular and molecular biology
- Biochemistry
Background:
- Ovarian theca-interstitial tissue growth regulation is crucial for ovarian function.
- Reactive oxygen species (ROS) influence cell signaling, including tissue growth and apoptosis.
- Previous studies showed antioxidants inhibit theca-interstitial cell proliferation.
Purpose of the Study:
- To investigate the effects of antioxidants on apoptosis in rat theca-interstitial cells.
- To explore the potential of antioxidants in managing conditions like PCOS.
Main Methods:
- Culturing rat theca-interstitial cells in a chemically defined medium.
- Treating cells with vitamin E succinate and ebselen (antioxidants).
- Assessing apoptosis via nuclear morphology, caspase 3/7 activity, and annexin V/propidium iodide staining.
Main Results:
- Both antioxidants induced significant apoptotic morphological changes (chromatin condensation, nuclear shrinkage).
- Antioxidants increased caspase 3/7 activity and annexin V staining, confirming apoptosis.
- Distinct antioxidants triggered apoptosis through different mechanisms.
Conclusions:
- Antioxidants induce apoptosis in ovarian mesenchyme cells.
- These findings provide mechanistic support for antioxidant use in treating PCOS.
- Antioxidants may help manage PCOS by targeting theca-interstitial cell overgrowth.
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