INVESTIGADORES
ORTEGA Hugo Hector
artículos
Título:
An imbalance between apoptosis and proliferation contributes to follicular persistence in polycystic ovaries in rats
Autor/es:
SALVETTI NR; PANZANI, CG; GIMENO EJ; NEME, L; ALFARO N; ORTEGA, HH
Revista:
Reproductive Biology and Endocrinology
Editorial:
BIOMED CENTRAL LTD
Referencias:
Año: 2009 vol. 7 p. 68 - 78
ISSN:
1477-7827
Resumen:
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.