Abstract
Objective: To evaluate the effects of resveratrol on growth and function of granulosa cells. Previously, we demonstrated that resveratrol exerts profound proapoptotic effects on theca-interstitial cells. Design: In vitro study. Setting: Research laboratory. Animal(s): Immature Sprague-Dawley female rats. Intervention(s): Granulosa cells were cultured in the absence or presence of resveratrol. Main Outcome Measure(s): DNA synthesis was determined by thymidine incorporation assay, apoptosis by activity of caspases 3/7, cell morphology by immunocytochemistry, steroidogenesis by mass spectrometry, antimüllerian hormone (AMH), and vascular endothelial growth factor (VEGF) expression by polymerase chain reaction and Western blot. Result(s): Resveratrol induced a biphasic effect on DNA synthesis, whereby a lower concentration stimulated thymidine incorporation and higher concentrations inhibited it. Additionally, resveratrol slightly increased the cell number and modestly decreased the activity of caspases 3/7 with no effect on cell morphology or progesterone production. However, resveratrol decreased aromatization and VEGF expression, whereas AMH expression remained unaltered. Conclusion(s): Resveratrol, by exerting cytostatic but not cytotoxic effects, together with antiangiogenic actions mediated by decreased VEGF in granulosa cells, may alter the ratio of theca-to-granulosa cells and decrease vascular permeability, and therefore may be of potential therapeutic use in conditions associated with highly vascularized theca-interstitial hyperplasia and abnormal angiogenesis, such as those seen in women with polycystic ovary syndrome.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1563-1573 |
| Number of pages | 11 |
| Journal | Fertility and Sterility |
| Volume | 98 |
| Issue number | 6 |
| DOIs | |
| State | Published - Dec 2012 |
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Keywords
- AMH
- Apoptosis
- granulosa cells
- proliferation
- resveratrol
- steroidogenesis
- VEGF
ASJC Scopus subject areas
- Obstetrics and Gynecology
- Reproductive Medicine
Cite this
Effects of resveratrol on growth and function of rat ovarian granulosa cells. / Ortega, Israel; Wong, Donna H.; Villanueva, Jesus A.; Cress, Amanda B.; Sokalska, Anna; Stanley, Scott D; Duleba, Antoni J.
In: Fertility and Sterility, Vol. 98, No. 6, 12.2012, p. 1563-1573.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effects of resveratrol on growth and function of rat ovarian granulosa cells
AU - Ortega, Israel
AU - Wong, Donna H.
AU - Villanueva, Jesus A.
AU - Cress, Amanda B.
AU - Sokalska, Anna
AU - Stanley, Scott D
AU - Duleba, Antoni J.
PY - 2012/12
Y1 - 2012/12
N2 - Objective: To evaluate the effects of resveratrol on growth and function of granulosa cells. Previously, we demonstrated that resveratrol exerts profound proapoptotic effects on theca-interstitial cells. Design: In vitro study. Setting: Research laboratory. Animal(s): Immature Sprague-Dawley female rats. Intervention(s): Granulosa cells were cultured in the absence or presence of resveratrol. Main Outcome Measure(s): DNA synthesis was determined by thymidine incorporation assay, apoptosis by activity of caspases 3/7, cell morphology by immunocytochemistry, steroidogenesis by mass spectrometry, antimüllerian hormone (AMH), and vascular endothelial growth factor (VEGF) expression by polymerase chain reaction and Western blot. Result(s): Resveratrol induced a biphasic effect on DNA synthesis, whereby a lower concentration stimulated thymidine incorporation and higher concentrations inhibited it. Additionally, resveratrol slightly increased the cell number and modestly decreased the activity of caspases 3/7 with no effect on cell morphology or progesterone production. However, resveratrol decreased aromatization and VEGF expression, whereas AMH expression remained unaltered. Conclusion(s): Resveratrol, by exerting cytostatic but not cytotoxic effects, together with antiangiogenic actions mediated by decreased VEGF in granulosa cells, may alter the ratio of theca-to-granulosa cells and decrease vascular permeability, and therefore may be of potential therapeutic use in conditions associated with highly vascularized theca-interstitial hyperplasia and abnormal angiogenesis, such as those seen in women with polycystic ovary syndrome.
AB - Objective: To evaluate the effects of resveratrol on growth and function of granulosa cells. Previously, we demonstrated that resveratrol exerts profound proapoptotic effects on theca-interstitial cells. Design: In vitro study. Setting: Research laboratory. Animal(s): Immature Sprague-Dawley female rats. Intervention(s): Granulosa cells were cultured in the absence or presence of resveratrol. Main Outcome Measure(s): DNA synthesis was determined by thymidine incorporation assay, apoptosis by activity of caspases 3/7, cell morphology by immunocytochemistry, steroidogenesis by mass spectrometry, antimüllerian hormone (AMH), and vascular endothelial growth factor (VEGF) expression by polymerase chain reaction and Western blot. Result(s): Resveratrol induced a biphasic effect on DNA synthesis, whereby a lower concentration stimulated thymidine incorporation and higher concentrations inhibited it. Additionally, resveratrol slightly increased the cell number and modestly decreased the activity of caspases 3/7 with no effect on cell morphology or progesterone production. However, resveratrol decreased aromatization and VEGF expression, whereas AMH expression remained unaltered. Conclusion(s): Resveratrol, by exerting cytostatic but not cytotoxic effects, together with antiangiogenic actions mediated by decreased VEGF in granulosa cells, may alter the ratio of theca-to-granulosa cells and decrease vascular permeability, and therefore may be of potential therapeutic use in conditions associated with highly vascularized theca-interstitial hyperplasia and abnormal angiogenesis, such as those seen in women with polycystic ovary syndrome.
KW - AMH
KW - Apoptosis
KW - granulosa cells
KW - proliferation
KW - resveratrol
KW - steroidogenesis
KW - VEGF
UR - http://www.scopus.com/inward/record.url?scp=84870341531&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84870341531&partnerID=8YFLogxK
U2 - 10.1016/j.fertnstert.2012.08.004
DO - 10.1016/j.fertnstert.2012.08.004
M3 - Article
C2 - 22959450
AN - SCOPUS:84870341531
VL - 98
SP - 1563
EP - 1573
JO - Fertility and Sterility
JF - Fertility and Sterility
SN - 0015-0282
IS - 6
ER -