Diminished PGE2 content, enhanced PGE2 release and defects in 3H-PGE2 transport in embryos from overtly diabetic rats

Abstract

Diminished PGE₂ levels in diabetic embryos are related to the development of malformations, and thus the aim of the present study was to determine whether PGE₂ levels are modified in rat embryos cultured in diabetic serum during organogenesis, and if PGE₂ content and release, and ³H-PGE₂ uptake and release, are altered in incubated diabetic embryos. Rats were made diabetic by steptozotocin (60 mg kg^–1) before mating. Control rat embryos cultured for 24 h (explantation Day 9) in the presence of diabetic serum showed diminished PGE₂ levels. When Day 10 diabetic embryos were incubated, embryo PGE₂ levels were lower, but the PGE₂ released to the incubation media was much higher than in controls. Uptake of ³H-PGE₂ by diabetic embryos was initially enhanced (5–10 min), then reached similar levels to controls (20–100 min). Release of ³H-PGE₂ previously incorporated during a 60-min incubation was greater in diabetic embryos than in controls. These results show diminished PGE₂ content in both diabetic and normal embryos cultured in the presence of diabetic serum, but suggest that diabetic embryos have the capability to produce and release high levels of PGE₂. The enhanced release of PGE₂ is probably the result of transport abnormalities, and leads to the elevated PGE₂ concentrations found in the incubating medium and to the diminished intraembryonic PGE₂ levels that alter embryonic development.