Peroxisomes are essential in cellular metabolism as their dysgenesis or defects in single enzymes or impairment of multiple peroxisomal enzymatic functions have been found in several inherited metabolic diseases with serious clinical sequelae. The assembly and formation of these cytoplasmic organelles constitute a major and intriguing research topic. In the present study the biogenesis of peroxisomes and the developmental patterns of their enzymes have been reviewed during embryonic and/or post-embryonic ontogenesis of lower (amphibians) and higher (avians, mammals) vertebrates. In developing vertebrates, epithelial cell differentiation is accompanied by increases in frequency and size of peroxisomes. The tissue-specific expression of peroxisomal enzymes contributes substantially to the biochemical maturation of epithelial cells. The relationship between biogenesis of peroxisomes, expression of peroxisomal enzymes and structural and functional cellular phenotype has also been investigated in differentiating epithelial cells along the crypt-villus axis of the adult rat intestine. Cytochemical studies at the ultrastructural level have provided evidence that peroxisomes are already present in proliferating cells of the intestinal crypt region before they begin to differentiate. Migration and differentiation of intestinal epithelial cells from crypt to villus compartments are marked by significant increases in number and size of catalase-positive structures. Increasing activity gradients from crypt to surface areas are found for the peroxisomal oxidases examined (enzymes of the peroxisomal beta-oxidation system, D-amino acid oxidase and polyamine oxidase). Thus, peroxisomes are more and more involved in oxidative metabolic pathways as intestinal epithelial cells differentiate. Finally, we have analyzed the peroxisomal behaviour in human neoplastic epithelial cells. The presence of peroxisomes has been cytochemically revealed in human breast and colon carcinomas. Peroxisomal enzyme specific activities are significantly lower in human breast and colon carcinomas than in the adjacent healthy mucosa. Furthermore, a relationship is found between the specific activities of some peroxisomal enzymes and the histological tumour grades.

The development of peroxisomes and expression of their enzymes were investigated in differentiating intestinal epithelial cells during their migration along the crypt-villus axis. Sequential cell populations harvested by a low-temperature method were identified by microscopy, determination of alkaline phosphatase and sucrase activities and incorporation of [3H]-thymidine into DNA. Ultrastructural cytochemistry after staining for catalase activity, revealed the presence of peroxisomes in undifferentiated stem cells located in the crypt region. Morphometry indicated that the number of these organelles increased as intestinal epithelial cells differentiate. Catalase activity was higher in the crypt cells than in the mature enterocytes harvested from villus tips. On the other hand, an increasing gradient of activity was observed from crypts to villus tips for peroxisomal oxidases, i.e. fatty acyl coA oxidase, D-amino acid oxidase and polyamine oxidase. These findings indicate that biogenesis of peroxisomes occurs during migration of intestinal epithelial cells along the crypt-villus axis and that peroxisomal oxidases contribute substantially to the biochemical maturation of enterocytes.

The appearance and development of peroxisomes and the expression of their enzymes in the human fetal intestine have been investigated between 11 and 22 weeks of gestation. In the youngest samples (11-16 weeks of age), cytochemistry at the ultrastructural level revealed the presence of rare, mostly circular peroxisomes. From 16 weeks of gestation onwards, an increase was noted in the number of peroxisomes. Two peroxisomal types were distinguished: round to oval forms and elongated and/or tailed organelles. Biochemical assays revealed that total and specific intestinal catalase activities increased gradually between 11 and 20 weeks of gestation. The activity of fatty acyl-CoA oxidase, the first enzyme of the peroxisomal β-oxidation system, was detectable as early as 11 weeks of gestation. Thereafter, total and specific activities of the enzyme increased steadily. Activities of other peroxisomal oxidases (D-amino acid oxidase, L-α-hydroxyacid oxidase) appeared more slowly in the fetal intestine during the period studied. This investigation establishes the presence and the morphological changes that occur in intestinal peroxisomes during human fetal development as well as the developmental patterns of associated enzymes.

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