Apoptosis in rat placenta is zone-dependent and stimulated by glucocorticoids

Apoptosis, or physiological cell death, is elevated in the placenta of huma n pregnancies complicated by fetal growth retardation, suggesting that plac ental apoptosis may be a key factor in the overall control of fete-placenta l growth. The present study used DNA internucleosomal fragmentation analysi s to characterize apoptosis in the two morphologically and functionally dis tinct regions of the rat placenta, the basal and labyrinth zones, during th e last week of pregnancy (Days 16, 22, and 23). In addition, because glucoc orticoids are potent inhibitors of fetoplacental growth and can stimulate a poptosis in other tissues, we examined whether dexamethasone treatment in v ivo induces placental apoptosis. DNA fragmentation was clearly evident in b oth placental zones at each stage of pregnancy, with higher levels evident in the basal zone compared with the labyrinth zone on Days 22 and 23. TUNEL analysis, which identifies dying cells in situ, demonstrated positive stai ning of cells in the basal zone, particularly giant trophoblast cells. Dexa methasone treatment increased DNA fragmentation in the basal zone but not t he labyrinth zone. Similarly, maternal treatment with carbenoxolone, which can enhance local concentrations of endogenous glucocorticoid by inhibition of 11 beta -hydroxysteroid dehydrogenase, also increased DNA fragmentation in the basal zone but not in the labyrinth zone. These effects of dexameth asone and carbenoxolone on placental apoptosis were associated; with reduce d placental and fetal weights. In conclusion, this study shows that apoptos is occurs in both zones of the rat placenta, particularly in the basal zone near term, and is elevated after increased glucocorticoid exposure in vivo . These data support the hypothesis that placental apoptosis is an importan t player in the regulation of fete-placental growth, and establish the rat as a useful model ten study the endocrine control of placental apoptosis.