Role of the DLL4-NOTCH system in PGF2alpha-induced luteolysis in the pregnant rat

Fatima Hernandez, Marina C. Peluffo, Richard Stouffer, Griselda Irusta, Marta Tesone

    Research output: Contribution to journalArticle

    17 Citations (Scopus)

    Abstract

    We investigated the expression and cell localization of NOTCH1, NOTCH4, and the delta-like ligand DLL4 in corpus luteum (CL) from pregnant rats during prostaglandin F2alpha (PGF2alpha)-induced luteolysis. We also examined serum progesterone (P4) and CL proteins related to apoptosis after local administration of the notch inhibitor N-[N-(3,5-difluorophenacetyl-L-alanyl)]-S-phenylglycine t-butyl ester (DAPT). Specific staining for NOTCH1 and NOTCH4 receptors was detected predominantly in large and small luteal cells. Furthermore, in line with the fact that the notch intracellular domain is translocated to the nucleus, where it regulates gene expression, staining was evident in the nuclei of luteal cells. In addition, we detected diffuse cytoplasmic immunostaining for DLL4 in small and large luteal cells, in accordance with the fact that DLL4 undergoes proteolytic degradation after receptor binding. The mRNA expression of Notch1, Notch4, and Dll4 in CL isolated on Day 19 of pregnancy decreased significantly after administration of PGF2alpha. Consistent with the mRNA results, administration of PGF2alpha to pregnant rats on Day 19 of pregnancy decreased the protein fragment corresponding to the cleaved forms of NOTCH1/4 CL receptors. In contrast, no significant changes were detected in protein levels for the ligand DLL4. The local intrabursal administration of DAPT decreased serum P4 levels and increased luteal levels of active caspase 3 and the BAX:BCL2 ratio 24 h after the treatment. These results support a luteotropic role for notch signaling to promote luteal cell viability and steroidogenesis, and they suggest that the luteolytic hormone PGF2alpha may act in part by reducing the expression of some notch system members.

    Original languageEnglish (US)
    Pages (from-to)859-865
    Number of pages7
    JournalBiology of Reproduction
    Volume84
    Issue number5
    DOIs
    StatePublished - May 2011

    Fingerprint

    Luteolysis
    Luteal Cells
    Dinoprost
    Corpus Luteum
    Staining and Labeling
    Pregnancy Proteins
    Ligands
    Messenger RNA
    Serum
    Caspase 3
    Progesterone
    Cell Survival
    Proteins
    Hormones
    Apoptosis
    Gene Expression
    Pregnancy

    Keywords

    • Apoptosis
    • Corpus luteum
    • Ovary
    • Pregnancy
    • Progesterone/progesterone receptor

    ASJC Scopus subject areas

    • Cell Biology

    Cite this

    Role of the DLL4-NOTCH system in PGF2alpha-induced luteolysis in the pregnant rat. / Hernandez, Fatima; Peluffo, Marina C.; Stouffer, Richard; Irusta, Griselda; Tesone, Marta.

    In: Biology of Reproduction, Vol. 84, No. 5, 05.2011, p. 859-865.

    Research output: Contribution to journalArticle

    Hernandez, Fatima ; Peluffo, Marina C. ; Stouffer, Richard ; Irusta, Griselda ; Tesone, Marta. / Role of the DLL4-NOTCH system in PGF2alpha-induced luteolysis in the pregnant rat. In: Biology of Reproduction. 2011 ; Vol. 84, No. 5. pp. 859-865.
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