Apoptosis in rat placenta is zone-dependent and stimulated by glucocorticoids.
Apoptosis, or physiological cell death, is elevated in the placenta of human pregnancies complicated by fetal growth retardation, suggesting that placental apoptosis may be a key factor in the overall control of feto-placental growth. The present study used DNA internucleosomal fragmentation analysis to characterize apoptosis in the two morphologically and functionally distinct regions of the rat placenta, the basal and labyrinth zones, during the last week of pregnancy (Days 16, 22, and 23). In addition, because glucocorticoids are potent inhibitors of feto-placental growth and can stimulate apoptosis in other tissues, we examined whether dexamethasone treatment in vivo induces placental apoptosis. DNA fragmentation was clearly evident in both 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 staining of cells in the basal zone, particularly giant trophoblast cells. Dexamethasone treatment increased DNA fragmentation in the basal zone but not the 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 dexamethasone and carbenoxolone on placental apoptosis were associated with reduced placental and fetal weights. In conclusion, this study shows that apoptosis 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 important player in the regulation of feto-placental growth, and establish the rat as a useful model to study the endocrine control of placental apoptosis.
Waddell
B J
BJ
Department of Anatomy & Human Biology, The University of Western Australia, Nedlands, Western Australia. bwaddell@anhb.uwa.edu.au
Hisheh
S
S
Dharmarajan
A M
AM
Burton
P J
PJ
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002229:Carbenoxolone / Q000494:pharmacology; D053938:DNA Fragmentation; D003907:Dexamethasone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D020567:Fetal Weight / Q000187:drug effects; D005865:Gestational Age; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors; D020287:In Situ Nick-End Labeling; D009929:Organ Size / Q000187:drug effects; D010920:Placenta / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D003907:Dexamethasone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D002229:Carbenoxolone