Prostaglandin F2alpha- and FAS-activating antibody-induced regression of the corpus luteum involves caspase-8 and is defective in caspase-3 deficient mice

Silvia F Carambula; James K Pru; Maureen P Lynch; Tiina Matikainen; Paulo Bayard D Gonçalves; Richard A Flavell; Jonathan L Tilly; Bo R Rueda

doi:10.1186/1477-7827-1-15

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Prostaglandin F2alpha- and FAS-activating antibody-induced regression of the corpus luteum involves caspase-8 and is defective in caspase-3 deficient mice

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Prostaglandin F2alpha- and FAS-activating antibody-induced regression of the corpus luteum involves caspase-8 and is defective in caspase-3 deficient mice

Silvia F Carambula, James K Pru, Maureen P Lynch, Tiina Matikainen, Paulo Bayard D Gonçalves, Richard A Flavell, Jonathan L Tilly and Bo R Rueda

Reproductive biology and endocrinology, Vol.1(1), pp.15-15

02/11/2003

DOI: https://doi.org/10.1186/1477-7827-1-15

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https://hdl.handle.net/2376/110700

PMCID: PMC152637

PMID: 12657159

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Abstract

Research

We recently demonstrated that caspase -3 is important for apoptosis during spontaneous involution of the corpus luteum (CL). These studies tested if prostaglandin F 2α (PGF 2α ) or FAS regulated luteal regression, utilize a caspase -3 dependent pathway to execute luteal cell apoptosis, and if the two receptors work via independent or potentially shared intracellular signaling components/pathways to activate caspase -3. Wild-type (WT) or caspase -3 deficient female mice, 25–26 days old, were given 10 IU equine chorionic gonadotropin (eCG) intraperitoneally (IP) followed by 10 IU human chorionic gonadotropin (hCG) IP 46 h later to synchronize ovulation. The animals were then injected with IgG (2 micrograms, i.v.), the FAS-activating antibody Jo2 (2 micrograms, i.v.), or PGF 2α (10 micrograms, i.p.) at 24 or 48 h post-ovulation. Ovaries from each group were collected 8 h later for assessment of active caspase -3 enzyme and apoptosis (measured by the TUNEL assay) in the CL. Regardless of genotype or treatment, CL in ovaries collected from mice injected 24 h after ovulation showed no evidence of active caspase -3 or apoptosis. However, PGF 2α or Jo2 at 48 h post-ovulation and collected 8 h later induced caspase -3 activation in 13.2 ± 1.8% and 13.7 ± 2.2 % of the cells, respectively and resulted in 16.35 ± 0.7% (PGF 2α ) and 14.3 ± 2.5% TUNEL-positive cells when compared to 1.48 ± 0.8% of cells CL in IgG treated controls. In contrast, CL in ovaries collected from caspase -3 deficient mice whether treated with PGF 2α , Jo2, or control IgG at 48 h post-ovulation showed little evidence of active caspase -3 or apoptosis. CL of WT mice treated with Jo2 at 48 h post-ovulation had an 8-fold increase in the activity of caspase -8, an activator of caspase -3 that is coupled to the FAS death receptor. Somewhat unexpectedly, however, treatment of WT mice with PGF 2α at 48 h post-ovulation resulted in a 22-fold increase in caspase -8 activity in the CL, despite the fact that the receptor for PGF 2α has not been shown to be directly coupled to caspase -8 recruitment and activation. We hypothesize that PGF 2α initiates luteolysis in vivo , at least in part, by increasing the bioactivity or bioavailability of cytokines, such as FasL and that multiple endocrine factors work in concert to activate caspase -3-driven apoptosis during luteolysis.

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Title: Prostaglandin F2alpha- and FAS-activating antibody-induced regression of the corpus luteum involves caspase-8 and is defective in caspase-3 deficient mice
Creators: Silvia F Carambula - Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts 02114, USA
James K Pru - Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts 02114, USA
Maureen P Lynch - Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts 02114, USA
Tiina Matikainen - Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts 02114, USA
Paulo Bayard D Gonçalves - Departamento De Clínica De Grandes Animais, Universidade Federal De Santa Maria, Faculdade de Medicina Veterinária, RS, Brazil
Richard A Flavell - Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven Connecticut 06510, USA
Jonathan L Tilly - Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts 02114, USA
Bo R Rueda - Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts 02114, USA
Publication Details: Reproductive biology and endocrinology, Vol.1(1), pp.15-15
Academic Unit: Animal Sciences, Department of
Publisher: BioMed Central; London
Identifiers: 99900547172301842
Language: English
Resource Type: Journal article