Caspase-3 in the rat ovary: localization and possible role in follicular atresia and luteal regression.
Apoptosis, the cellular mechanism of ovarian follicular atresia and luteal regression, is triggered by the activation of a proteolytic cascade of cysteine aspartate-specific proteases (caspases). The principle downstream effector of cell death is caspase-3, but little is known about the role or regulation of this enzyme in ovarian apoptosis. Two substrates of caspase-3, actin and poly(ADP-ribose) polymerase (PARP), are inhibitors of DNase I, which is the endonuclease responsible for ovarian apoptotic DNA degradation. We therefore investigated the proteolytic cleavage of actin and PARP as well as the localization of caspase-3 during follicular atresia (induced by gonadotropin withdrawal) and luteal regression (induced by prostaglandin F2alpha) in the rat ovary. Apoptotic DNA degradation was evident during both follicular atresia and luteal regression, but cleavage of PARP and actin was observed only during luteal regression. Caspase-3 was localized in luteal cells of healthy corpora lutea (CL) and in theca, but not in granulosa cells of healthy follicles. However, caspase-3 immunostaining was evident in granulosa cells of atretic follicles in a pattern similar to that of the localization of granulosa cell death. There was no difference between healthy and apoptotic CL in the distribution or intensity of caspase-3 staining. These results demonstrate that the cleavage of actin and PARP are not necessary for activation of apoptotic DNA degradation during ovarian apoptosis. In addition, the presence of caspase-3 in granulosa cells of atretic, but not healthy, follicles suggests that the expression of this enzyme is regulated by gonadotropin and may be up-regulated as part of the apoptotic process in granulosa cells.
Boone
D L
DL
Department of Obstetrics & Gynecology, University of Ottawa, Ottawa Civic Hospital Loeb Research Institute, Ontario, Canada.
Tsang
B K
BK
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000032:analysis* / Q000378:metabolism*; D015237:Dinoprost / Q000494:pharmacology; D005260:Female; D005496:Follicular Atresia / Q000502:physiology*; D006107:Granulosa Cells / Q000201:enzymology; D003341:Luteolysis / Q000502:physiology*; D010053:Ovary / Q000166:cytology / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013799:Theca Cells / Q000201:enzymology
D006063:Chorionic Gonadotropin; D015237:Dinoprost; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases