Prostaglandins

and Medicine

1:

265-266,

1978.

ELEVATED CONCENTRATIONS OF 6-KETO-PROSTAGLANDIN

F1 IN FETAL AND MATERNAL PLASMA AND IN AMNIOTIC FLUID DURING OVINE PARTURIT!?ON Mitchell, D.A. Ellwood, Anne B.M. Anderson and A.C. Turnbull (reprint requests to MDM)

M.D.

Nuffield Department of Obstetrics and Gynaecology University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DU. U.K. (PGF2 ) in ovine The initial suggestion of a role for prostaglandin F2 parturition was based on the evidence of elevated ute?ine vegous plasma levels at parturition (1). More recently it has been shown that the concentration of prostaglandin E (PGE) in fetal plasma is raised shortly before delivery and prostaglandin levels in amniotic fluid are also elevated at this time (2). It is possible that these prostaglandins play a significant part in the control of fetal and placental hemodynamics (for reviews see 2). The discovery of prostacyclin (3) another metabolite of the prostaglandin endoperoxides, has aroused considerable interest and widespread re-evaluation of previous concepts of prostaglandin function. In sheep it has already been demonstrated that 6-keto-prostaglandin F1 (6-keto-PGFI - the stable metabolite of prostacyclin (4) ) is the maj8r prostaglandyn produced by non-pregnant uterine in maternal tissue (5). We report here the first measurements of 6-keto-PGF1 and fetal plasma and in amniotic fluid during late pregnancy and garturition in sheep. Maternal utero-ovarian venous, fetal inferior vena caval and amniotic fluid catheters were inserted into a sheep at laparotomy by strictly aseptic techniques on day 119 of pregnancy. After allowing 7 days for recovery parturition was induced by the intrafetal infusion of dexamethasone at 1 mg/24 hr into one of the twin fetuses (1). This procedure allowed a longer period of experimental observation which was used for serial sampling of maternal and fetal blood and amniotic fluid. Fetal blood was taken from the infused twin. 6-keto-PGF1 was measured by a specific radioimmunoassay (6). Twin lambs were born alive 15l"hrs after starting the infusion of dexamethasone. The typical fall in plasma levels of progesterone and rise in levels of oestradiol 17B associated with dexamethasone induced delivery (1) occurred (data not shown). Concentrations of 6-keto-PGF1 in fetal and maternal plasma and amniotic fluid throughout the induction of pgrturition are shown in Fig.1. The last samples of maternal and fetal p.lasma were obtained 1 hr before delivery and the last sample of amniotic fluid 1.5 hr before delivery. It is apparent that during active labour there was a marked increase in the concentration of 6-keto-PGFlo in all three fluids investigated.

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Concentration of 6-keto-PGFI in (0) utero-ovarian venous Figure 1 plasma, (0) fetal venous plasma and (A)oamniotic fluid during dexamethasone induced parturition. These results represent the first data on concentrations of 6-keto-PGF1 in plasma or amniotic fluid during late ovine pregnancy and suhsequent tregds with induced parturition. Indeed these may be the first data on circulating levels of 6-keto-PGF1 during parturition in any species. There is a clear indication of ra:sed levels in both the maternal and fetal compartments which may play a crucial part in the mechanisms in which prostaglandins have previously been thought to have a role (2). It is beyond the scope of this report to speculate further on these preliminary findings but our ongoing studies continue the investigation of possible roles for prostacyclin in ovine parturition. We thank Mrs L. Clover and Mrs H. Hodgson for expert assistance with these studies and Dr J.E. Pike (Upjohn Co., Kalamazoo, U.S.A.) for the gift of authentic 6-keto-PGFI . DAE is supported by an MRC scholarship. MDM acknowledges receipt 8f the Staines Medical Research Fellowship (Exeter College, Oxford). This work was supported by an MRC (UK) Grant awarded to ACT. REFERENCES 1. Liggins GC., Fairclough RJ, Grieves SA, Kendall JZ, Knox BS. The mechanism of initiation of parturition in the ewe. Recent Progress in Hormone Research 29: 111, 1973 2. Prostaglandins and Perinatal Medicine. Advances in Prostaglandin and Thromboxane Research Vol 4. (F. Coceani, PM Olley eds) Raven Press,New York,1978 3. Moncada S, Gryglewski R, Bunting S, Vane JR. An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature 263, 663, 1976 Johnson RA, Morton DR, Kinner JH, German RR, McGuire JC, Sun FF,Whittaker N, 4 Bunting S, Salmon J, Moncada S. Vane JR. The chemical structure of prostaglandin X (prostacyclin). Prostaglandins 12: 915, 1976 5. Jones RL, Poyser NL, Wilson NH. Production of 6-oxo-prostaglandin F1 by rat, guinea-pig and sheep uteri in vitro. British Journal of Pharmacolggy 59: 436P, 1977 6. Mitchell MD. A sensitive radioimmunoassay for 6-keto-prostaglandin Fr : preliminary observations on circulating concentrations. Prostaglandins an8 Medicine 1: 13, 1978. 266

Elevated concentrations of 6-keto-prostaglandin F1alpha in fetal and maternal plasma and in amniotic fluid during ovine parturition.

Prostaglandins and Medicine 1: 265-266, 1978. ELEVATED CONCENTRATIONS OF 6-KETO-PROSTAGLANDIN F1 IN FETAL AND MATERNAL PLASMA AND IN AMNIOTIC FL...
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