EPITHELIAL GROWTH OF THE SMALL INTESTINE OCCURS BY BOTH CRYPT FISSION and CRYPT HYPERPLASIA DURING INFANCY and CHILDHOOD IN HUMANS

Abstract

Our previous study has shown physiological crypt hyperplasia during infancy. Another mechanism of epithelial growth is crypt fission but this has not been investigated in humans. During crypt fission, crypts divide by unzipping from the base. A founder crypt divides into two daughter crypts with duplication of stem cells in the base. We investigated both crypt fission and crypt hyperplasia in infants (aged < 2 years, n = 4), children (aged 2–10 years, n = 7) and adults (n = 14) who had endoscopy for irritability/reflux oesophagitis in whom intestinal disease was unlikely. Duodenal biopsies were taken during endoscopy and villus area, crypt length, mitotic count per crypt and percentage of bifid crypts (a measure of crypt fission) were assessed by a microdissection technique. Villus area and crypt length correlate with villous and crypt enterocyte population, respectively. Mean ± SE villus area in infants, children and adults was 0.298 ± 0.009 mm2, 0.251 ± 0.029 mm2, and 0.257 ± 0.024 mm2, respectively, although no biopsies were available from neonates or infants < 6 months of age. Mean ± SE crypt length in infants, children, and adults was 284 ± 6, 299 ± 16 and 208 ± 13 μm, respectively. Mean ± SE mitotic count per crypt in infants, children and adults was 4.2 ± 0.1, 4.3 ± 0.8 and 2.1 ± 0.3, respectively. Thus, physiological crypt hyperplasia was present in both infants and children with longer crypts and higher proliferation of crypt cells. The mean ± SE percentage of bifid crypts in infants, children and adults was 9.1 ± 1.0, 5.0 ± 0.9 and 1.8 ± 0.5%, respectively. We conclude that crypt fission is predominantly elevated during infancy and to a lesser extent during childhood, whereas crypt hyperplasia is elevated equally during both infancy and childhood. We speculate this is due to differences in gene expression of positive and negative growth factors and their receptors.