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Local effects of the sphingosine 1‐phosphate on prostaglandin F2alpha‐induced luteolysis in the pregnant rat
Author(s) -
Hernandez Fatima,
Peluffo Marina C.,
Bas Diana,
Stouffer Richard L.,
Tesone Marta
Publication year - 2009
Publication title -
molecular reproduction and development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 105
eISSN - 1098-2795
pISSN - 1040-452X
DOI - 10.1002/mrd.21083
Subject(s) - luteolysis , corpus luteum , apoptosis , luteal phase , medicine , endocrinology , sphingosine 1 phosphate , biology , prostaglandin f2alpha , estrous cycle , caspase 3 , prostaglandin , prostaglandin e2 , tumor necrosis factor alpha , andrology , sphingosine , programmed cell death , ovary , hormone , receptor , biochemistry
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. Mol. Reprod. Dev. 76: 1153–1164, 2009. © 2009 Wiley‐Liss, Inc.