It is proposed that amnion apoptosis requires: (1) Activation of cyclooxygenase-2; (2) Funneling of PGDH2, the cyclooxygenase product, to PGD2, and thereafter to metabolites of thePGJ2 series; and (3) Activation of PPARy nuclear receptors which control genes critical to apoptosis. A study of the dependence of amnion cell apoptosis upon this specific prostaglandin pathway is proposed. Activators of cyclooxygenase which initiate amnion apoptosis will be compared to those that do not initiate apoptosis in terms of: (1) Activation of transcription, translation, and activity of cyclooxygenase 1 and 2; (2) Spectrum of the primary prostaglandin metabolites produced (PGE2, PGF2, PGD2, etc.); (3) Production of apoptotic prostaglandin metabolite (PGE/PGJ); and (4) Activation of specific genes via PPARy. The effects upon apoptosis of activation and inhibition at each step of this prostaglandin cascade will be determined.
