Effects of oxidants and antioxidants on proliferation of endometrial stromal cells.
OBJECTIVE
To evaluate the effects of oxidative stress and antioxidants on proliferation of endometrial stromal cells.


METHODS
In vitro study.


METHODS
Academic laboratory.


METHODS
Women, with and without endometriosis, of reproductive age.


METHODS
Culture of endometrial stromal cells with antioxidants or with agents inducing oxidative stress.


METHODS
Proliferation of endometrial stromal cells as determined by thymidine incorporation assay and 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) assay.


RESULTS
Antioxidants induced a dose-dependent inhibition of thymidine incorporation: vitamin E succinate was inhibitory at 10-100 microM (by 43%-95%), ebselen at 10-30 microM (by 29%-77%), and N-acetylcysteine at 10-30 mM (by 52%-85%). In contrast, modest oxidative stress induced by hypoxanthine/xanthine oxidase (1 mM/3-30 microU/mL) stimulated proliferation by 40%-62%. H2O2 (1 microM) increased DNA synthesis by 56%. Comparable findings were obtained using MTT proliferation assay. Antioxidants inhibited proliferation: vitamin E succinate (100 microM) by 91%, ebselen (30 microM) by 81%, and N-acetylcysteine (30 mM) by 95%. Hypoxanthine/xanthine oxidase (1 mM/30 microU/mL) and H2O2 (1 microM) stimulated growth by 122% and 58%, respectively.


CONCLUSIONS
Reactive oxygen species may modulate growth of endometrial stroma. Under pathologic conditions such as endometriosis, increased oxidative stress and depletion of antioxidants may contribute to excessive growth of endometrial stromal cells.
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Nastaran
N
Foyouzi
Murat
M
Berkkanoglu
Aydin
A
Arici
Jakub
J
Kwintkiewicz
Daniel
D
Izquierdo
Antoni J
AJ
Duleba
D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D016022:Case-Control Studies; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004715:Endometriosis / Q000378:metabolism / Q000473:pathology*; D004717:Endometrium / Q000473:pathology*; D005260:Female; D006801:Humans; D016877:Oxidants / Q000008:administration & dosage / Q000494:pharmacology*; D018384:Oxidative Stress; D017154:Stromal Cells / Q000473:pathology*; D013936:Thymidine / Q000037:antagonists & inhibitors / Q000378:metabolism
D000975:Antioxidants; D016877:Oxidants; D004247:DNA; D013936:Thymidine