Local effects of the sphingosine 1-phosphate on prostaglandin F2alpha-induced luteolysis in the pregnant rat

Fatima Hernandez, Marina C. Peluffo, Diana Bas, Richard Stouffer, Marta Tesone

    Research output: Contribution to journalArticle

    14 Citations (Scopus)

    Abstract

    Since the regression of the corpus luteum (CL) occurs via a tightly controlled apoptotic process, studies were designed to determine if local administration of the antiapoptotic agent sphingosine 1-phosphate (S1P) effectively blocks the luteolytic action of prostaglandin F-2alpha (PGF-2α). On day 19 of pregnancy, 2 hr before systemic PGF-2α administration, rats were injected intrabursa with either S1P or vehicle (control). The activity of four caspases, which contribute to the initial (caspase-2, -8, and -9) and final (caspase-3) events in apoptosis was measured in pooled CL from four individual ovaries at 0 and 4 hr after PGF-2α injection. The expression of the phosphorylated form of AKT (pAKT) and tumor necrosis factor-alpha (TNF-α) was analyzed by ELISA. In addition, cell death was evaluated by electronic microscopy (EM) in CL 4 and 36 hr after PGF-2α injection. The activity of caspase-2, -3, and -8 was significantly greater by 4 hr after PGF-2α, but not caspase-9 activity. In contrast, expression of pAKT and TNF-α decreased significantly. Administration of S1P suppressed (P <0.05) these effects, decreasing caspase activities and increasing pAKT and TNF-α expression. The administration of S1P also significantly decreased the percentage of luteal apoptotic cells induced by PGF-2α. PGF-2α treatment increased the prevalence of luteal cells with advanced signs of apoptosis (i.e., multiple nuclear fragments, chromatin condensation, or apoptotic bodies). S1P treatment suppressed these changes and increased the blood vessel density. These results suggest that S1P blocks the luteolytic effect of the PGF-2α by decreasing caspase-2, -3, and -8 activities and increasing AKT phosphorylation and TNF-α expression.

    Original languageEnglish (US)
    Pages (from-to)1153-1164
    Number of pages12
    JournalMolecular Reproduction and Development
    Volume76
    Issue number12
    DOIs
    StatePublished - Dec 2009

    Fingerprint

    Luteolysis
    Dinoprost
    Prostaglandins F
    Caspase 2
    Tumor Necrosis Factor-alpha
    Caspase 3
    Luteal Cells
    Corpus Luteum
    Caspases
    Luteolytic Agents
    Apoptosis
    Injections
    sphingosine 1-phosphate
    Caspase 9
    Caspase 8
    Chromatin
    Blood Vessels
    Microscopy
    Ovary
    Cell Death

    ASJC Scopus subject areas

    • Genetics
    • Developmental Biology
    • Cell Biology

    Cite this

    Local effects of the sphingosine 1-phosphate on prostaglandin F2alpha-induced luteolysis in the pregnant rat. / Hernandez, Fatima; Peluffo, Marina C.; Bas, Diana; Stouffer, Richard; Tesone, Marta.

    In: Molecular Reproduction and Development, Vol. 76, No. 12, 12.2009, p. 1153-1164.

    Research output: Contribution to journalArticle

    Hernandez, Fatima ; Peluffo, Marina C. ; Bas, Diana ; Stouffer, Richard ; Tesone, Marta. / Local effects of the sphingosine 1-phosphate on prostaglandin F2alpha-induced luteolysis in the pregnant rat. In: Molecular Reproduction and Development. 2009 ; Vol. 76, No. 12. pp. 1153-1164.
    @article{ec2b5bded8f44176b1c2cb848da6daa5,
    title = "Local effects of the sphingosine 1-phosphate on prostaglandin F2alpha-induced luteolysis in the pregnant rat",
    abstract = "Since the regression of the corpus luteum (CL) occurs via a tightly controlled apoptotic process, studies were designed to determine if local administration of the antiapoptotic agent sphingosine 1-phosphate (S1P) effectively blocks the luteolytic action of prostaglandin F-2alpha (PGF-2α). On day 19 of pregnancy, 2 hr before systemic PGF-2α administration, rats were injected intrabursa with either S1P or vehicle (control). The activity of four caspases, which contribute to the initial (caspase-2, -8, and -9) and final (caspase-3) events in apoptosis was measured in pooled CL from four individual ovaries at 0 and 4 hr after PGF-2α injection. The expression of the phosphorylated form of AKT (pAKT) and tumor necrosis factor-alpha (TNF-α) was analyzed by ELISA. In addition, cell death was evaluated by electronic microscopy (EM) in CL 4 and 36 hr after PGF-2α injection. The activity of caspase-2, -3, and -8 was significantly greater by 4 hr after PGF-2α, but not caspase-9 activity. In contrast, expression of pAKT and TNF-α decreased significantly. Administration of S1P suppressed (P <0.05) these effects, decreasing caspase activities and increasing pAKT and TNF-α expression. The administration of S1P also significantly decreased the percentage of luteal apoptotic cells induced by PGF-2α. PGF-2α treatment increased the prevalence of luteal cells with advanced signs of apoptosis (i.e., multiple nuclear fragments, chromatin condensation, or apoptotic bodies). S1P treatment suppressed these changes and increased the blood vessel density. These results suggest that S1P blocks the luteolytic effect of the PGF-2α by decreasing caspase-2, -3, and -8 activities and increasing AKT phosphorylation and TNF-α expression.",
    author = "Fatima Hernandez and Peluffo, {Marina C.} and Diana Bas and Richard Stouffer and Marta Tesone",
    year = "2009",
    month = "12",
    doi = "10.1002/mrd.21083",
    language = "English (US)",
    volume = "76",
    pages = "1153--1164",
    journal = "Molecular Reproduction and Development",
    issn = "1040-452X",
    publisher = "Wiley-Liss Inc.",
    number = "12",

    }

    TY - JOUR

    T1 - Local effects of the sphingosine 1-phosphate on prostaglandin F2alpha-induced luteolysis in the pregnant rat

    AU - Hernandez, Fatima

    AU - Peluffo, Marina C.

    AU - Bas, Diana

    AU - Stouffer, Richard

    AU - Tesone, Marta

    PY - 2009/12

    Y1 - 2009/12

    N2 - Since the regression of the corpus luteum (CL) occurs via a tightly controlled apoptotic process, studies were designed to determine if local administration of the antiapoptotic agent sphingosine 1-phosphate (S1P) effectively blocks the luteolytic action of prostaglandin F-2alpha (PGF-2α). On day 19 of pregnancy, 2 hr before systemic PGF-2α administration, rats were injected intrabursa with either S1P or vehicle (control). The activity of four caspases, which contribute to the initial (caspase-2, -8, and -9) and final (caspase-3) events in apoptosis was measured in pooled CL from four individual ovaries at 0 and 4 hr after PGF-2α injection. The expression of the phosphorylated form of AKT (pAKT) and tumor necrosis factor-alpha (TNF-α) was analyzed by ELISA. In addition, cell death was evaluated by electronic microscopy (EM) in CL 4 and 36 hr after PGF-2α injection. The activity of caspase-2, -3, and -8 was significantly greater by 4 hr after PGF-2α, but not caspase-9 activity. In contrast, expression of pAKT and TNF-α decreased significantly. Administration of S1P suppressed (P <0.05) these effects, decreasing caspase activities and increasing pAKT and TNF-α expression. The administration of S1P also significantly decreased the percentage of luteal apoptotic cells induced by PGF-2α. PGF-2α treatment increased the prevalence of luteal cells with advanced signs of apoptosis (i.e., multiple nuclear fragments, chromatin condensation, or apoptotic bodies). S1P treatment suppressed these changes and increased the blood vessel density. These results suggest that S1P blocks the luteolytic effect of the PGF-2α by decreasing caspase-2, -3, and -8 activities and increasing AKT phosphorylation and TNF-α expression.

    AB - Since the regression of the corpus luteum (CL) occurs via a tightly controlled apoptotic process, studies were designed to determine if local administration of the antiapoptotic agent sphingosine 1-phosphate (S1P) effectively blocks the luteolytic action of prostaglandin F-2alpha (PGF-2α). On day 19 of pregnancy, 2 hr before systemic PGF-2α administration, rats were injected intrabursa with either S1P or vehicle (control). The activity of four caspases, which contribute to the initial (caspase-2, -8, and -9) and final (caspase-3) events in apoptosis was measured in pooled CL from four individual ovaries at 0 and 4 hr after PGF-2α injection. The expression of the phosphorylated form of AKT (pAKT) and tumor necrosis factor-alpha (TNF-α) was analyzed by ELISA. In addition, cell death was evaluated by electronic microscopy (EM) in CL 4 and 36 hr after PGF-2α injection. The activity of caspase-2, -3, and -8 was significantly greater by 4 hr after PGF-2α, but not caspase-9 activity. In contrast, expression of pAKT and TNF-α decreased significantly. Administration of S1P suppressed (P <0.05) these effects, decreasing caspase activities and increasing pAKT and TNF-α expression. The administration of S1P also significantly decreased the percentage of luteal apoptotic cells induced by PGF-2α. PGF-2α treatment increased the prevalence of luteal cells with advanced signs of apoptosis (i.e., multiple nuclear fragments, chromatin condensation, or apoptotic bodies). S1P treatment suppressed these changes and increased the blood vessel density. These results suggest that S1P blocks the luteolytic effect of the PGF-2α by decreasing caspase-2, -3, and -8 activities and increasing AKT phosphorylation and TNF-α expression.

    UR - http://www.scopus.com/inward/record.url?scp=70350439433&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=70350439433&partnerID=8YFLogxK

    U2 - 10.1002/mrd.21083

    DO - 10.1002/mrd.21083

    M3 - Article

    VL - 76

    SP - 1153

    EP - 1164

    JO - Molecular Reproduction and Development

    JF - Molecular Reproduction and Development

    SN - 1040-452X

    IS - 12

    ER -