Ontogeny and regulation of ovine placental prostaglandin E2 synthase.
Recent evidence suggests that ovine placental output of prostaglandin (PG) E2 rises through late gestation partly because of a direct effect of cortisol on PGH2 synthase 2 (PGHS-2) expression and activity within trophoblast tissue. Synthesis of PGE2 is also dependent, however, on PGE2 synthase (PGES), which converts PGH2 to PGE2. We hypothesized that PGES is expressed in the ovine placenta, and that, similar to PGHS-2, expression increases through gestation and is regulated positively by cortisol. Placental tissues from pregnant ewes in mid and late gestation, at term, and during early and active labor were analyzed to determine the gestational profile of PGES. The regulation of PGES expression was assessed in placental tissues from pregnant ewes in which intrafetal cortisol infusion was administered in late gestation, in the presence or absence of an aromatase inhibitor, to block the cortisol-stimulated rise in estradiol. Expression of PGES was analyzed by in situ hybridization, Western blot analysis, and immunohistochemistry. In the placentome, PGES localized to fetal trophoblast cells and endothelial cells in maternal blood vessels, consistent with its contribution to the rise in placental PGE2 output toward the onset of labor and with a role of PGE2 in the local regulation of uteroplacental blood flow, respectively. Expression of PGES mRNA and protein increased with gestation. However, there was no significant further change with labor or during cortisol infusion in the presence or absence of a rise in fetal plasma estradiol, in contrast to reported changes in PGHS-2. These results suggest that PGES is not coregulated with PGHS-2 in the sheep placenta at term. The progressive increase in PGES, however, likely contributes to the rise in circulating PGE2 in the fetus in late pregnancy.
Martin
R L
RL
Canadian Institutes for Health Research Groups in Fetal and Neonatal Health and Development, Department of Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
Whittle
W L
WL
Holloway
A C
AC
Gyomorey
S
S
Gibb
W
W
Lye
S
S
Challis
J R G
JR
D000818:Animals; D015153:Blotting, Western; D015232:Dinoprostone / Q000097:blood; D004958:Estradiol / Q000097:blood; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005865:Gestational Age; D006854:Hydrocortisone / Q000494:pharmacology; D017403:In Situ Hybridization; D019746:Intramolecular Oxidoreductases / Q000032:analysis / Q000235:genetics*; D007743:Labor, Obstetric; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D000071876:Prostaglandin-E Synthases; D012333:RNA, Messenger / Q000032:analysis; D012756:Sheep
D012333:RNA, Messenger; D004958:Estradiol; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone; D006854:Hydrocortisone