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

HERNANDEZ F; PELUFFO MC; BAS D; STOUFFER RL; TESONE M

MOLECULAR REPRODUCTION AND DEVELOPMENT

WILEY-LISS, DIV JOHN WILEY & SONS INC

Año: 2009 vol. 76 p. 1153 - 1164

1040-452X

Since the regression of the corpus luteum (CL) occurs via a tightly controlled apoptoticprocess, studies were designed to determine if local administration of the antiapoptoticagent sphingosine 1-phosphate (S1P) effectively blocks the luteolytic action of prostaglandinF-2alpha (PGF-2a). On day 19 of pregnancy, 2 hr before systemic PGF-2aadministration, rats were injected intrabursa with either S1P or vehicle (control). Theactivity 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 individualovaries at 0 and 4 hr after PGF-2a injection. The expression of the phosphorylatedform ofAKT(pAKT) and tumor necrosis factor-alpha (TNF-a) was analyzed by ELISA.In addition, cell death was evaluated by electronic microscopy (EM) in CL 4 and 36 hrafter PGF-2a injection. The activity of caspase-2, -3, and -8 was significantly greaterby 4 hr after PGF-2a, but not caspase-9 activity. In contrast, expression of pAKT andTNF-a decreased significantly. Administration of S1P suppressed (P<0.05) theseeffects, decreasing caspase activities and increasing pAKT and TNF-a expression.The administration of S1P also significantly decreased the percentage of lutealapoptotic cells induced by PGF-2a. PGF-2a treatment increased the prevalence ofluteal cells with advanced signs of apoptosis (i.e., multiple nuclear fragments,chromatin condensation, or apoptotic bodies). S1P treatment suppressed thesechanges and increased the blood vessel density. These results suggest that S1Pblocks the luteolytic effect of the PGF-2a by decreasing caspase-2, -3, and -8activities and increasing AKT phosphorylation and TNF-a expression.