title: Antioxidants induce apoptosis of rat ovarian theca-interstitial cells.
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.
authors.affiliation: Department of Gynecology and Obstetrics, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Izabela J
authors.initials: IJ
authors.lastname: Rzepczynska
authors.forename: Nastaran
authors.initials: N
authors.lastname: Foyouzi
authors.forename: Piotr C
authors.initials: PC
authors.lastname: Piotrowski
authors.forename: Ciler
authors.initials: C
authors.lastname: Celik-Ozenci
authors.forename: Amanda
authors.initials: A
authors.lastname: Cress
authors.forename: Antoni J
authors.initials: AJ
authors.lastname: Duleba
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000235:genetics / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001393:Azoles / Q000494:pharmacology*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053179:Caspase 7 / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D054833:Isoindoles; D016566:Organoselenium Compounds / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013799:Theca Cells / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D024505:Tocopherols / Q000494:pharmacology*
chemical_list: D017304:Annexin A5; D000975:Antioxidants; D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; C042986:ebselen; D053148:Caspase 3; D053179:Caspase 7; D024505:Tocopherols