Endocrine pancreas development in growth-retarded human fetuses.
Glucose intolerance in adults born with intrauterine growth retardation (IUGR) may involve peripheral insulin resistance and/or abnormal endocrine pancreas development during fetal life. We quantified insulin-containing cells in deceased human fetuses with IUGR (<10th percentile, n = 21) or normal growth (control fetuses, n = 15). Paraffin-embedded pancreatic tissues from fetuses older than 32 weeks were obtained from two fetopathology departments. Mean gestational age was 36 weeks in both groups. Tissues with lysis and those fetuses with defects, aneuploidy, or genetic abnormalities were excluded. For each subject, six pancreatic sections spaced evenly throughout the organ were immunostained with anti-insulin antibody. Total tissue and insulin-positive areas were measured by computer-assisted quantitative morphometry. Results were expressed in percentages. To evaluate islet morphogenesis, the percentages of beta-cells inside and outside islets were determined. Islet density was similar in the two groups (P = 0.86). The percentage of pancreatic area occupied by beta-cells (beta-cell fraction) was not correlated with gestational age (r = 0.06 and P = 0.97 in IUGR fetuses; r = 0.12 and P = 0.67 in control fetuses) or body weight (r = 0.16 and P = 0.47 in IUGR fetuses; r = 0.24 and P = 0.39 in control fetuses). Mean beta-cell fraction was 2.53% in the IUGR fetuses and 2.86% in the control fetuses (P = 0.47). The percentage of beta-cells located within islets was identical in the two groups (mean 35%). Our data militate against a primary developmental pancreatic abnormality in human IUGR, leaving peripheral insulin resistance as the most likely mechanism of glucose intolerance in adults born with IUGR.
Béringue
Frédérique
F
Institut National de la Santé et de la Recherche Médicale (INSERM) Unit 457, Robert Debré Teaching Hospital, Paris, France.
Blondeau
Bertrand
B
Castellotti
Marie Claire
MC
Bréant
Bernadette
B
Czernichow
Paul
P
Polak
Michel
M
D015331:Cohort Studies; D005314:Embryonic and Fetal Development; D005317:Fetal Growth Retardation / Q000150:complications / Q000196:embryology*; D020567:Fetal Weight; D005333:Fetus / Q000033:anatomy & histology / Q000378:metabolism; D005865:Gestational Age; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000196:embryology*; D009929:Organ Size; D014652:Vascular Diseases / Q000150:complications / Q000196:embryology
D007328:Insulin