The late gestation increase in circulating ACTH and cortisol in the fetal sheep is suppressed by intracerebroventricular infusion of recombinant ovine leptin

The obese gene product leptin, originally characterised as an adipocyte hormone coordinating the behavioural and neuroendocrine responses to starvation, is expressed in fetal adipocytes and placental trophoblast cells and is present in the fetal circulation. Concentrations of leptin in fetal blood correlate with fetal bodyweight and fat mass. In post-natal life, leptin conveys information about calorie intake and the state of adipose tissue energy stores, and plasma leptin levels are generally inversely correlated with hypothalamo-pituitary adrenal (HPA) activity. Late fetal life is characterised by increasing HPA activity that prepares the fetus for extrauterine life and initiates the endocrine cascade leading to parturition. We have investigated the hypothesis that leptin in the fetal circulation can inhibit the fetal HPA axis, thereby providing a mechanism by which the fetus can determine the fine timing of parturition as long as it is adequately nourished and growing appropriately. Here we show that a 5-day intracerebroventricular infusion of leptin to the sheep fetus in late gestation inhibits the pre-parturient rise in ACTH and cortisol concentrations, and that this seems to be a centrally mediated effect

Prostaglandins in the plasma and amniotic fluid of rhesus monkeys during pregnancy and after intra uterine foetal death

Prostaglandin F (PGF) was measured in amniotic fluid, and 13,14 dihydro 15 ketoprostaglandin F(2α) (PGFM) was measured in maternal peripheral venous plasma and amniotic fluid of rhesus monkeys during late pregnancy. 13,14 Dihydro 15 keto PGF(2α) was determined in the maternal peripheral venous plasma of two animals following intrauterine foetal death. The mean concentration of PGF and PGFM in amniotic fluid increased fourfold during the last 5 days of pregnancy. This increase was associated with an increase in the oestrone concentration in amniotic fluid and in maternal plasma. In normal pregnancy there was no increase in PGFM levels in the maternal peripheral vein, up to 1-2 days prepartum. After intra uterine death, progesterone concentration in the maternal peripheral vein was unaltered, but oestrone and oestradiol declined. In plasma samples taken within 12 h of delivery, the concentration of PGFM was raised. It is concluded that an increase in prostaglandin production accompanies delivery at normal term, and at delivery past term following intra uterine foetal death

Administration of extra-amniotic arachidonic acid and the suppression of uterine prostaglandin synthesis during pregnancy in the rhesus monkey

After extra-amniotic treatment of pregnant rhesus monkeys premature parturition was induced in 4 given 2.5 mg PGE-2; none of the 4 monkeys given 100 mg arachidonic acid were affected. The concentrations of PGE, PGF or 13,14-dihydro-15-oxo-PGF did not change after arachidonic acid treatment, but all increased after PGE-2. It is suggested that the availability of substrate, arachidonic acid, is not a major factor governing the control of PG synthesis but that the latter is suppressed during pregnancy

Effects of periconceptional undernutrition on the initiation of parturition in sheep

In sheep, parturition is initiated by increased fetal hypothalamic-pituitary-adrenal axis ( HPAA) activity leading to PGE(2) and PGF(2alpha) production and a rise in the 17beta-estradiol-progesterone (E-2/P-4) ratio. Uteroplacental PG production can also increase fetal HPAA activity. Periconceptional maternal undernutrition accelerates fetal HPAA maturation resulting in preterm labor. We determined whether preterm labor was preceded by an increase in PG concentrations and E-2/P-4 ratio and whether these increases preceded or followed the corresponding rise in cortisol concentrations. Singleton-bearing ewes were nourished ad libitum (N, n = 9) or undernourished (UN, n = 10) to reduce maternal weight by 15% from - 61 days (d) to + 30 d after mating with ad libitum intake thereafter. Paired maternal and fetal blood samples were collected from 126 d until delivery. Half the UN group delivered prematurely ( > 2 SD below mean gestation for the flock). PG and cortisol concentrations and E-2/P-4 ratio increased before delivery in the same way in both groups. However, the increases occurred 7 - 10 d earlier in UN than in N animals. In both UN and N fetuses cortisol concentrations rose before fetal and maternal PG concentrations and maternal E-2/P-4 ratio. Periconceptional maternal undernutrition induces preterm delivery in sheep by advancing the expected prepartum rise in cortisol and PG concentrations and E-2/P-4 ratio. The rise in fetal cortisol concentration precedes the rise in fetal and maternal PG concentrations and maternal E-2/P-4 ratio, suggesting that the underlying mechanism is likely to be acceleration of fetal HPAA maturation, resulting in initiation of the normal process of parturition