Abstract

Prostaglandin F_{2 α} (PGF_{2 α}) is a key factor in the triggering of the regression of the corpus luteum (CL). Furthermore, it has been reported that Slit/Robo signaling is involved in the regulation of luteolysis. However, the interactions between PGF_{2 α} and Slit/Robo in the progression of luteolysis remain to be established. This study was designed to determine whether luteolysis is regulated by the interactions of PGF_{2 α} and Slit/Robo in the mouse CL. Real-time PCR and immunohistochemistry results showed that Slit2 and its receptor Robo1 are highly and specifically co-expressed in the mouse CL. Functional studies showed that Slit/Robo participates in mouse luteolysis by enhancing cell apoptosis and upregulating caspase3 expression. Both in vitro and in vivo studies showed that PGF_{2 α} significantly increases the expression of Slit2 and Robo1 during luteolysis through protein kinase C-dependent ERK1/2 and P38 MAPK signaling pathways, whereas an inhibitor of Slit/Robo signaling significantly decreases the stimulating effect of PGF_{2 α} on luteolysis. These findings indicate that Slit/Robo signaling plays important roles in PGF_{2 α}-induced luteolysis by mediating the PGF_{2 α} signaling pathway in the CL.