title: Increase in 15-hydroxyprostaglandin dehydrogenase activity in the ovine placentome at parturition and effect of oestrogen.
abstract: Type 1 NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase (PGDH) is the key enzyme for metabolism of active primary prostaglandins to inactive forms in gestational tissues. The present study examined the activity and immunolocalization of PGDH in the ovine placenta, fetal membranes and uterus over the latter half of pregnancy, and its potential regulation by oestradiol. Placenta, fetal membranes and myometrium were collected from sheep with known single insemination dates on days 70, 100 and 135 of gestation and in active labour demonstrated by electromyographic activity. In addition, chronically catheterized fetuses were infused with oestradiol (100 microgram kg(-1) per 24 h) (n = 5) or saline vehicle into the fetus from day 120 to day 125. PGDH activity measured in placental extracts remained constant from day 70 to day 135 of gestation, and then significantly (P < 0.05) increased by 300% in active labour. Immunoreactive PGDH was localized in the placentome at all stages and was present predominantly in the fetal component of the placentome in uninucleate, but not in binucleate, trophoblast cells. Similarly, in the fetal membranes PGDH immuno-reactivity was present in the uninucleate trophoblast but not in the binucleate cells of the chorion. PGDH immunostaining was also present in the endometrial luminal epithelium, in the smooth muscle of the myometrium, and the glandular epithelium of the cervix. Infusion of oestradiol into the fetal circulation from day 120 to day 125 of gestation had no effect on placental PGDH activity. Immunohistochemistry was used to localize oestrogen receptor alpha in intrauterine tissues to investigate further the failure of oestradiol to increase PGDH activity. Immunoreactive oestrogen receptor alpha was not present in the fetal component of the placenta, although it was expressed in adjacent maternal-derived cells. It is concluded that (1) PGDH activity increases in late gestation; (2) PGDH is expressed in uninucleate trophoblast cells in the ovine placenta and fetal membranes, and also in the maternal endometrial epithelium and stroma, myometrium and cervix; (3) oestrogen receptor alpha is not expressed in fetal cells in the placenta or fetal membranes; and (4) the increase in PGDH activity is not regulated by oestradiol administered to the fetus.
authors.affiliation: Department of Reproductive and Developmental Sciences, Obstetrics and Gynaecology Section, University of Edinburgh, Edinburgh, UK.
authors.forename: S C
authors.initials: SC
authors.lastname: Riley
authors.forename: R
authors.initials: R
authors.lastname: Leask
authors.forename: J V
authors.initials: JV
authors.lastname: Selkirk
authors.forename: R W
authors.initials: RW
authors.lastname: Kelly
authors.forename: A N
authors.initials: AN
authors.lastname: Brooks
authors.forename: D C
authors.initials: DC
authors.lastname: Howe
mesh_terms: D000818:Animals; D002584:Cervix Uteri / Q000201:enzymology; D004717:Endometrium / Q000201:enzymology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005865:Gestational Age; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism*; D007150:Immunohistochemistry; D007743:Labor, Obstetric / Q000378:metabolism*; D009215:Myometrium / Q000201:enzymology; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D011453:Prostaglandins / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000032:analysis; D012756:Sheep / Q000378:metabolism*; D014327:Trophoblasts / Q000187:drug effects / Q000201:enzymology
chemical_list: D011453:Prostaglandins; D011960:Receptors, Estrogen; D004958:Estradiol; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase