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The IGF system is one of the most important endocrine and paracrine growth factor systems that regulate fetal and placental growth. We hypothesized that intrauterine growth restriction (IUGR) in guinea pigs is mediated by the altered expression of IGFs and/or IGF binding protein (BP) mRNAs in tissues and is related to growth of specific tissues. IUGR was induced by unilateral uterine artery ligation on day 30 of gestation, and fetal plasma, amniotic fluid and tissue samples were collected at 55–57 days (term about 68 days) from paired IUGR and control fetuses (n=6). Western ligand blotting and immunoblotting were used to compare IGFBP levels in plasma and amniotic fluid. Total RNA was extracted from placenta and fetal tissues, and the relative abundance of IGF-II and IGFBP-1–6 mRNA was determined by Northern blotting, using species-specific probes where available. IUGR fetuses had decreased (P<0.01, by Student’s t-test) placental weight and body weight with an increase in the brain:liver weight ratio. The principal IGFBPs in fetal plasma migrated at 40–35, 30 and 25 kDa and were identified as IGFBP-3, -2 and -4 respectively. IUGR was associated with elevated plasma IGFBP-2 and IGFBP-4 and reduced IGFBP-3 levels. IGFBPs were detected at low levels in amniotic fluid of control fetuses but at higher levels in IUGR fetuses. In IUGR placentae, there was a small increase in IGFBP-4 mRNA (P<0.05). IGFBP-2 mRNA increased (P<0.001) in liver of IUGR fetuses. IGF-II and IGFBP mRNA expression did not change in fetal muscle. The results are consistent with reduced IGF action, directly or through inhibition by IGFBPs, particularly by circulating and tissue IGFBP-2, as a potential causal factor in decreased growth of the placenta and certain fetal tissues.
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Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Headington, Oxford, OX3 9DU
(Received 9 February 1978)
It has been shown that prostaglandins play an important role in the mechanism of parturition in many species, including the goat (Currie & Thorburn, 1977; Thorburn, Challis & Robinson, 1977). Recently we have demonstrated that intra-uterine tissues from pregnant goats, when superfused in vitro, produce prostaglandins E and F (PGE, PGF) and 13,14-dihydro-15-oxo-prostaglandin F at various rates (Mitchell, Flint, Robinson & Thorburn, 1978). The exciting discoveries of two potent prostaglandin-like compounds, thromboxane A2 (TXA2; Hamberg, Svensson & Samuelsson, 1975) and prostacyclin (PGI2; Moncada, Gryglewski, Bunting & Vane, 1976), have radically altered our thinking on prostaglandins and basic data are urgently required concerning these compounds. Since prostaglandin endoperoxides are the immediate precursors of both prostaglandins and TXA2 (and PGI2) and since TXA2 has been shown to cause contraction of a number
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Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Headington, Oxford, 0X3 9DU
(Received 21 July 1978)
It now seems likely that prostaglandins play an important role in the mechanisms of parturition in many species (Flint & Hillier, 1976; Thorburn, Challis & Robinson, 1977), including the goat (Thorburn, Nicol, Bassett, Shutt & Cox, 1972; Currie & Thorburn, 1977). This evidence has been further strengthened by the demonstration of the production of prostaglandins in vitro by uterine tissues from goats during late pregnancy (Mitchell, Flint, Robinson & Thorburn, 1978b). The recent discovery of prostacyclin (Moncada, Gryglewski, Bunting & Vane, 1976) has added a new dimension to prostaglandin research since in some biological systems it has a greater potency than other prostaglandins (Moncada et al. 1976; Omini, Moncada & Vane, 1977). Prostacyclin is highly unstable in aqueous media and degrades spontaneously to 6-oxo-prostaglandin F1α (6-oxo-PGF1α; Johnson, Morton, Kinner, Gorman,
