Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Protects the Ovary of Mice Against Mitoxantrone Cytotoxicity

Abstract

PACAP is a pleiotropic polypeptide with cytotrophic, anti-inflammatory, and anti-apoptotic activities. Mitoxantrone (MTX) is a chemotherapeutic drug used for treatment of multiple sclerosis. My hypothesis is that PACAP will protect the granulosa cells of the ovarian follicle from cytotoxic cell death caused by MTX treatment. A total number of 27 mice were assigned to 3 groups; MTX, MTX + PACAP, and control. TUNEL staining, caspase-3 assay, and H&E staining were used to visualize the granulosa cells in ovary sections. H&E staining showed that MTX treatment reduced the number of developing follicles. Positive TUNEL in granulosa cells of ovary treated with MTX confirmed cell damage by MTX. Follicles in the MTX + PACAP group were TUNEL negative. The caspase-3 staining was negative in all groups. These observations suggest that MTX causes granulosa cell death from DNA damage but not due to apoptosis, and PACAP protects the granulosa cells from DNA damage.