Cyclooxygenase-2-derived endogenous prostacyclin reduces apoptosis and enhances embryo viability in mouse.
The role of prostaglandins (PGs) in apoptosis in preimplantation mice embryo development is reported in this study. It is known that apoptosis plays a very important role in normal mice embryo development. Very few reports are available on this subject. Embryos (6-8 cells) were cultured in the presence of a selective cyclooxygenase (COX)1 inhibitor (SC560), a selective COX2 inhibitor (NS398) and a selective prostacyclin synthase (PGIS) inhibitor (U51605) in a 48-h culture. In another experiment, culture media were supplemented with prostaglandin E2 (PGE2) and prostaglandin I2 (PGI2 or prostacyclin) analogues. The apoptosis was evaluated by detection of active caspase-3. It was strongly detected in the presence of selective COX-2 and PGIS inhibitors, which can be decreased by a PGI2 analogue. In our embryo transfer experiment, the implantation rate decreased with exposure to either the COX2 or the PGIS inhibitor which is increased further after PGI2 supplementation. The level of PGI2 is also higher at the 8-16-cell stage, compaction and blastocyst stage than PGE2. All these results indicate that COX2-derived PGI2 plays an important role in preimplantation embryo development and acts as an antiapopetic factor in in vitro culture.
Pakrasi
Pranab Lal
PL
Embryo Physiology Laboratory, Center of Advanced Study, Department of Zoology, Banaras Hindu University, Varanasi 221005, India. pakrasi@bhu.ac.in
Jain
Anil K
AK
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001755:Blastocyst / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D053148:Caspase 3 / Q000096:biosynthesis / Q000378:metabolism; D061945:Caspase Inhibitors; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism*; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D046149:Embryo Culture Techniques / Q000379:methods; D010064:Embryo Implantation / Q000187:drug effects; D004624:Embryo Transfer; D047108:Embryonic Development / Q000187:drug effects; D011464:Epoprostenol / Q000096:biosynthesis / Q000502:physiology*; D005260:Female; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009578:Nitrobenzenes / Q000494:pharmacology*; D011247:Pregnancy; D011463:Prostaglandins H / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*
D061945:Caspase Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D009578:Nitrobenzenes; D011463:Prostaglandins H; D011720:Pyrazoles; C115461:SC 560; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; C015014:azo analog I; D003577:Cytochrome P-450 Enzyme System; D011464:Epoprostenol; D051546:Cyclooxygenase 2; C505409:Casp3 protein, mouse; D053148:Caspase 3; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase