The effects of cortisol on the growth rate of the sheep fetus during late gestation

Using indwelling crown-rump length (CRL)-measuring devices, the growth rate of sheep fetuses was monitored during late gestation and after experimental manipulation of fetal plasma cortisol by exogenous infusion and fetal adrenalectomy. In intact control fetuses, the increment in CRL declined progressively during the last 20-25 days of gestation: mean +/- S.E.M. values fell from 5.5 +/- 0.4 mm/day (n=12) at 21-25 days before delivery to 2.5 +/- 0.3 mm/day (n=12) in the last 5 days before birth (P<0.01). These changes closely parallelled the normal prepartum increase in fetal plasma cortisol which rose from 19.3 +/- 3.3 nmol/l (n=10) at 21-25 days before birth to 177.4 +/- 19.0 nmol/l (n=10) in the final 5 days before delivery (P<0.01). When this cortisol surge was prevented by fetal adrenalectomy, there was no decrease in CRL increment towards normal term: mean CRL increment in the 5 days before normal term (4.8 +/- 0.6 mm/day, n=5) was similar to that observed at 21-25 days before term (4.7 +/- 0.4 mm/day, n=5). At delivery at term, the body weight (4.116 +/- 0.280 kg, n=5) and CRL (51.9 +/- 1.7 cm, n=5) of the adrenalectomized fetuses were significantly greater than the corresponding values in their sham-operated controls (2.877 +/- 0.070 kg and 47.1 +/- 1.6 cm, n=6, respectively). In contrast with the sham-operated controls, plasma glucose and insulin levels in the adrenalectomized fetuses decreased towards term. Infusion of cortisol into the preterm fetus for 5 days increased fetal plasma cortisol to term levels and decreased the CRL increment to a value (1.8 +/- 0.5 mm/day, n=8) which was similar to that observed in untreated controls during the last 5 days before spontaneous delivery at term (2.1 +/- 0.3 mm/day, n=6). There were no significant alterations in the fetal arterial concentrations of plasma glucose or insulin in response to fetal cortisol infusion. When all the data were combined irrespective of treatment or proximity to delivery, the fetal plasma concentrations of cortisol (P<0.001) and glucose (P<0.04), but not-insulin (P>0.05), had a significant effect on the fetal CRL increment measured over 5-day periods during the last 25-30 days of gestation. These findings show that cortisol inhibits growth of the axial skeleton in the sheep fetus during late gestation. They also indicate that the prepartum cortisol surge may be responsible for the normal decline in fetal growth rate observed towards term in this species.