Presented at the Neonatal Society 2002 Spring Meeting.
Gopalakrishnan G, Dandrea J, Broughton-Pipkin F, Stephenson T, Symonds ME
School of Human Development, Queens Medical Centre, Nottingham NG7 2UH
Introduction: In sheep, modest maternal nutrient restriction over the period of rapid placental growth followed by normal feeding to term results in offspring with a larger placenta and increased expression of the glucocorticoid receptor in a range of fetal tissues (1, 2). These individuals could be at increased risk of diseases including hypertension and obesity in later life. As yet the underlying mechanisms are unknown although it has been suggested that fetal overexposure to maternal glucocorticoids may program events in utero contributing to enhanced glucocorticoid action throughout later life (3). The aim of this study was to determine the consequences of maternal undernutrition on maternal plasma cortisol levels throughout gestation.
Study design: Ten Welsh Mountain ewes were individually housed from 28 days gestation. Five ewes were nutrient restricted (NR) (3.5 MJ/day) until 80 days gestation and five fed a control (C) diet (6.8-7.5 MJ/day). After 80 days gestation, until term, all animals consumed 6.8-7.5 MJ/day, sufficient to meet their metabolisable energy requirements for maintenance and growth of the conceptus throughout pregnancy. Maternal blood samples were taken at hourly intervals over an 8h period once every 20 days from 42 to 140 days gestation (term = 147 days). Total plasma cortisol levels were assessed using a radioimmunoassay.
Results: During the period of nutrient restriction both pre- and post-prandial plasma cortisol were significantly (p<0.001) lower in NR compared with C ewes (e.g. Figure 1). This difference was no longer apparent when previously NR ewes were fed the same amount of feed as C i.e. after 80 days gestation. The results are expressed as medians and interquartile ranges of both groups.
Figure 1. Maternal preprandial plasma cortisol concentrations during pregnancy (NR, n=5; C, n=5)
Conclusion: Nutrient restriction resulted in a persistent decline in maternal cortisol that was no longer apparent following restoration of normal feeding. A reduction in maternal cortisol may act to conserve available energy from utilisation by maternal tissues thereby maximising its availability to the fetus. It is not expected to result in excess fetal exposure to cortisol.
Acknowledgements: G. Gopalakrishnan is supported by a British Heart Foundation studentship.
References
1. Heasman L, Clarke L, Firth K, Stephenson T, Symonds ME. Pediatr. Res. 1998; 44, 546-551.
2. Whorwood CB, Firth KM, Budge H, Symonds ME. Endocrinology 2001; 142, 2854-2864.
3. Dodic M, May N, Wintour EM, Coughlan JP. Clin. Sci. 1998; 94, 149-155.