Thyroid hormones are important regulators of fetal growth, although their mechanism of action remains unclear. This study investigated the effect of hypothyroidism on pancreatic β-cell development in foetal sheep.
All procedures were carried out under the UK Animals (Scientific Procedures) Act 1986. Under general anaesthesia between 105 and 110 days of gestation (days; term ~145 days), one twin fetus was thyroidectomised (TX), while the other was sham-operated as a control (n=19 ewes). After maternal euthanasia, umbilical arterial blood was taken from both foetuses at either 129 or 143 days (n=38). After foetal euthanasia, foetuses were weighed, measured and tissues collected. The whole fetal pancreas was weighed, fixed in 4% paraformaldehyde and embedded in paraffin wax. Pancreatic β-cells were identified immunohistochemically with an insulin antibody and their mass was calculated using the Cavalieri estimator (Visiopharm, Denmark). Plasma insulin, triiodothyronine (T3) and thyroxine (T4) concentrations were measured by ELISA or RIA. Data (mean±S.E.M.) were assessed by two-way ANOVA followed by Tukeys post hoc test.
In TX foetuses, plasma T3 and T4 concentrations were at the lower limit of assay detection (T3, 6.7 pg/ml; T4, 7.6 ng/ml) at both ages. There were no differences in absolute body or pancreas weight between TX and sham foetuses at either age. At 143 days, limb lengths, lungs, heart, stomach and small intestine of TX foetuses were growth retarded, while the kidneys and perirenal adipose tissue were significantly enlarged, compared with sham foetuses (P<0.05).
Plasma insulin levels were significantly higher in TX foetuses at both 129 day (sham: 92±60 ng/l; TX: 129±33 ng/l; P<0.05) and 143 days (sham: 56±10 ng/l; TX: 168±24 ng/l; P<0.05). Relative β-cell mass to body weight was significantly greater in TX foetuses at both 129 days (sham: 47±4 mg/kg; TX: 79±6 mg/kg; P<0.05) and 143 days (sham: 46±7 mg/kg; TX: 75±10 mg/kg; P<0.05). The results indicate that the thyroid hormone have an important role in the growth and development of foetal pancreatic islets.