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An imbalance between apoptosis and proliferation contributes to follicular persistence in polycystic ovaries in rats

BACKGROUND: Cystic ovarian disease is an important cause of infertility that affects bovine, ovine, caprine and porcine species and even human beings. Alterations in the ovarian micro-environment of females with follicular cysts could alter the normal processes of proliferation and programmed cell d...

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Autores principales: Salvetti, Natalia R, Panzani, Carolina G, Gimeno, Eduardo J, Neme, Leandro G, Alfaro, Natalia S, Ortega, Hugo H
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2713246/
https://www.ncbi.nlm.nih.gov/pubmed/19570211
http://dx.doi.org/10.1186/1477-7827-7-68
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author Salvetti, Natalia R
Panzani, Carolina G
Gimeno, Eduardo J
Neme, Leandro G
Alfaro, Natalia S
Ortega, Hugo H
author_facet Salvetti, Natalia R
Panzani, Carolina G
Gimeno, Eduardo J
Neme, Leandro G
Alfaro, Natalia S
Ortega, Hugo H
author_sort Salvetti, Natalia R
collection PubMed
description BACKGROUND: Cystic ovarian disease is an important cause of infertility that affects bovine, ovine, caprine and porcine species and even human beings. Alterations in the ovarian micro-environment of females with follicular cysts could alter the normal processes of proliferation and programmed cell death in ovarian cells. Thus, our objective was to evaluate apoptosis and proliferation in ovarian cystic follicles in rats in order to investigate the cause of cystic follicle formation and persistence. METHODS: We compared the number of in situ apoptotic cells by TUNEL assay, expression of active caspase-3 and members of Bcl-2 family by immunohistochemistry; and cell proliferation by the expression of the proliferation markers: PCNA and Ki-67. RESULTS: The proliferation index was low in granulosa of tertiary and cystic follicles of light exposed rats when compared with tertiary follicles of control animals, while in theca interna only cystic follicles presented low proliferation index when compared with tertiary follicles (p < 0.05). The granulosa of cysts exhibited a similar cell DNA fragmentation to early atretic follicles. In the granulosa and theca interna, active caspase-3 shown similar immunostaining levels in tertiary and cystic follicles (p < 0.05). The granulosa cells presented high expression of Bcl-2, Bcl-xL and Bcl-w in the tertiary and cystic follicles with diminishing intensity in the atretic follicles, except with Bcl-w where the intensity was maintained in the atretic follicles (p < 0.05). The expression of Bax was weak in the healthy and cystic follicles. In the theca interna, Bcl-2 expression was the same as the pattern found in the granulosa; no differences were found between tertiary and cystic follicles from both groups for Bcl-xL and Bcl-w. The expression of Bax in this layer was higher in the tertiary follicles of the treated animals (p < 0.05) while the values for cystic follicles were similar to those in the tertiary follicles of controls. The theca externa showed low expression of the pro and anti-apoptotic proteins. CONCLUSION: These results show that the combination of weak proliferation indices and low apoptosis observed in follicular cysts, could explain the cause of the slow growth of cystic follicles and the maintenance of a static condition without degeneration, which leads to their persistence. These alterations may be due to structural and functional modifications that take place in these cells and could be related to hormonal changes in animals with this condition.
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spelling pubmed-27132462009-07-21 An imbalance between apoptosis and proliferation contributes to follicular persistence in polycystic ovaries in rats Salvetti, Natalia R Panzani, Carolina G Gimeno, Eduardo J Neme, Leandro G Alfaro, Natalia S Ortega, Hugo H Reprod Biol Endocrinol Research BACKGROUND: Cystic ovarian disease is an important cause of infertility that affects bovine, ovine, caprine and porcine species and even human beings. Alterations in the ovarian micro-environment of females with follicular cysts could alter the normal processes of proliferation and programmed cell death in ovarian cells. Thus, our objective was to evaluate apoptosis and proliferation in ovarian cystic follicles in rats in order to investigate the cause of cystic follicle formation and persistence. METHODS: We compared the number of in situ apoptotic cells by TUNEL assay, expression of active caspase-3 and members of Bcl-2 family by immunohistochemistry; and cell proliferation by the expression of the proliferation markers: PCNA and Ki-67. RESULTS: The proliferation index was low in granulosa of tertiary and cystic follicles of light exposed rats when compared with tertiary follicles of control animals, while in theca interna only cystic follicles presented low proliferation index when compared with tertiary follicles (p < 0.05). The granulosa of cysts exhibited a similar cell DNA fragmentation to early atretic follicles. In the granulosa and theca interna, active caspase-3 shown similar immunostaining levels in tertiary and cystic follicles (p < 0.05). The granulosa cells presented high expression of Bcl-2, Bcl-xL and Bcl-w in the tertiary and cystic follicles with diminishing intensity in the atretic follicles, except with Bcl-w where the intensity was maintained in the atretic follicles (p < 0.05). The expression of Bax was weak in the healthy and cystic follicles. In the theca interna, Bcl-2 expression was the same as the pattern found in the granulosa; no differences were found between tertiary and cystic follicles from both groups for Bcl-xL and Bcl-w. The expression of Bax in this layer was higher in the tertiary follicles of the treated animals (p < 0.05) while the values for cystic follicles were similar to those in the tertiary follicles of controls. The theca externa showed low expression of the pro and anti-apoptotic proteins. CONCLUSION: These results show that the combination of weak proliferation indices and low apoptosis observed in follicular cysts, could explain the cause of the slow growth of cystic follicles and the maintenance of a static condition without degeneration, which leads to their persistence. These alterations may be due to structural and functional modifications that take place in these cells and could be related to hormonal changes in animals with this condition. BioMed Central 2009-07-01 /pmc/articles/PMC2713246/ /pubmed/19570211 http://dx.doi.org/10.1186/1477-7827-7-68 Text en Copyright © 2009 Salvetti et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Salvetti, Natalia R
Panzani, Carolina G
Gimeno, Eduardo J
Neme, Leandro G
Alfaro, Natalia S
Ortega, Hugo H
An imbalance between apoptosis and proliferation contributes to follicular persistence in polycystic ovaries in rats
title An imbalance between apoptosis and proliferation contributes to follicular persistence in polycystic ovaries in rats
title_full An imbalance between apoptosis and proliferation contributes to follicular persistence in polycystic ovaries in rats
title_fullStr An imbalance between apoptosis and proliferation contributes to follicular persistence in polycystic ovaries in rats
title_full_unstemmed An imbalance between apoptosis and proliferation contributes to follicular persistence in polycystic ovaries in rats
title_short An imbalance between apoptosis and proliferation contributes to follicular persistence in polycystic ovaries in rats
title_sort imbalance between apoptosis and proliferation contributes to follicular persistence in polycystic ovaries in rats
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2713246/
https://www.ncbi.nlm.nih.gov/pubmed/19570211
http://dx.doi.org/10.1186/1477-7827-7-68
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