Impact of Placental Restriction on the Development of the Sympathoadrenal System

Abstract

We have investigated the impact of chronic restriction of placental function on circulating catecholamine concentrations and responses to the indirectly acting, sympathomimetic amine, tyramine, in the fetal sheep in late gestation. In 10 ewes, endometrial caruncles or placental placentation sites were removed before conception (placental restriction (PR) group). Fetal sheep in the PR group were hypoxemic throughout late gestation and growth-restricted (3.02 +/- 0.35 kg) when compared with control fetal sheep (4.30 +/- 0.29 kg; n = 8) at 140 d of gestation. Fetal plasma concentrations of noradrenaline and adrenaline were higher (p < 0.05) in the PR (7.06 +/- 3.17 pmol/mL and 2.89 +/- 2.01 pmol/mL, respectively) than in the control group (3.55 +/- 0.54 pmol/mL and 1.30 +/- 0.48 pmol/mL, respectively) throughout late gestation. Plasma noradrenaline, but not adrenaline concentrations, increased significantly between 110 and 140 d of gestation in both the PR and control group, and there was a significant inverse relationship between plasma noradrenaline and arterial PO2 in the PR and control groups (plasma noradrenaline = 12.34 - 0.40 PO2). In the PR group, plasma noradrenaline increased (p < 0.05) after tyramine infusion from 4.51 +/- 1.28 pmol/mL to a peak of 19.40 +/- 3.56 pmol/mL. In the control group, noradrenaline increased from 2.08 +/- 0.30 pmol/mL to a peak of 12.23 +/- 1.67 pmol/mL after tyramine infusion. There was no difference, however, in the maximal proportional changes in plasma noradrenaline concentrations in the PR (319 +/- 55%) and control (449 +/- 100%) groups after tyramine. We conclude that the most likely source of the increased plasma catecholamines in the PR group is enhanced catecholamine synthesis and secretion from developing sympathetic neurons.

Fetal growth restriction: adaptations and consequences

“…The source of the increase in circulating noradrenaline concentrations during chronic or intermittent restriction of placental function may be either increased secretion from the fetal adrenal medulla, extra adrenal chromaffin tissue or sympathetic neurones. Intrafetal infusion of tyramine, which acts to displace noradrenaline from catecholamine-containing vesicles within postganglionic sympathetic neurones, results in a significantly greater increase in plasma noradrenaline in placentally restricted sheep than it does in control sheep fetuses (Simonetta et al, 1997). However, when these noradrenaline responses were expressed in relation to basal circulating concentrations, there was no difference in the fold changes in noradrenaline in response to tyramine between the placentally restricted and control animals.…”

“…In control animals, there is an inverse relationship between adrenaline and arterial pO 2 , such that a decrease in arterial pO 2 results in an increase in circulating adrenaline concentrations (Simonetta et al, 1997). In contrast, in the placentally restricted group, a decrease in arterial pO 2 is associated with a relative suppression, rather than a stimulation, of plasma adrenaline concentrations.…”

“…The increase in circulating catecholamines is important in the initiation and co-ordination of a range of fetal physiological responses to hypoxic stress (Giussani et al, 1994). Plasma noradrenaline concentrations were significantly higher in chronically hypoxaemic, growthrestricted sheep fetuses than in control sheep fetuses between day 110 and day 140 of gestation (Simonetta et al, 1997). Covariate analysis demonstrated that at any given arterial pH value, plasma noradrenaline concentrations were about 2.9 pmol ml -1 higher in the placentally restricted than in the control group.…”

“…For every 1 mmHg decrease in arterial pO 2 , noradrenaline increased by 0.4 pmol ml -1 during basal conditions in both the placentally restricted and control groups. Throughout late gestation, the prevailing mean arterial pO 2 was approximately 8 mmHg lower in the placentally restricted group than in the control group and, therefore, would account for the difference in noradrenaline concentrations of about 3.2 pmol ml -1 between the groups (Simonetta et al, 1997). Therefore, it appears that chronic hypoxaemia is the major factor contributing to the increase in circulating noradrenaline concentrations in the placentally restricted group in late gestation.…”

Impact of periconceptional nutrition on maternal and fetal leptin and fetal adiposity in singleton and twin pregnancies

“…The fetal arterial blood gas variables measured across late gestation in fetuses in all of the nutritional groups were in the normal range previously reported for healthy fetuses in late gestation (9,29). Fetal arterial blood samples (3.5 ml) were collected in chilled heparinized tubes (125 IU; Sarstedt, South Australia, Australia) three times per week between 0800 and 1100 for the measurement of plasma glucose, insulin, and leptin concentrations throughout late gestation.…”