Proliferation, differentiation and morphogenesis of fetal rat glandular stomach transplanted under the kidney capsule of syngeneic hosts

Abstract

Undifferentiated glandular stomach tissue fragments from 16.5-day fetal rats were transplanted under the kidney capsule of syngeneic adult rats, and the proliferation, differentiation and morphogenesis of the transplanted tissues were investigated. Gastric epithelial cells began to invaginate 3-4 days after the transplantation and immature glands were formed after 1 week. During the period, there was a gradual increase in the expression of pepsinogen and cathepsin E, markers of cytodifferentiation of the stomach epithelia, both at protein and mRNA levels. Cathepsin E was weakly expressed in undifferentiated gastric epithelial cells at 16.5 days of gestation, and a higher level of the expression was observed in differentiated epithelia of the transplants. In contrast, the pepsinogen-producing cells first appeared around days 3-4 after transplantation and gradually increased in number to about 30% of the epithelial cells and became localized at the bottom of the gland. During the period of the experiment up to 1 month, the pepsinogen-producing cells were all positive for class III mucin and cathepsin E, indicating the immature character of these cells. In addition, no parietal cells were observed. When the tissue fragments were transplanted into adrenalectomized animals, the epithelial differentiation and morphogenesis was suppressed, but its proliferation was enhanced. The observed changes were reversed by hydrocortisone replacement. These results suggest that the development of the 16.5-day fetal stomach is regulated intrinsically to a certain extent by the genetic program of the cells involved and various gastric functions develop in the absence of luminal stimulation, stage-specific systemic hormonal change, neuronal regulation or other systemic influences, and that glucocorticoids modulate the developmental program of the fetal stomach tissues.

Two-Month Glucocorticoid Treatment Increases Proliferation in the Stomach and Large Intestine of Rats

“…Previous observations also documented analogous changes in the stomach and colon [1, 2, 4, 5, 6, 7, 9, 10, 12, 14, 15, 28, 29]. It should be noted that a decrease in the values of all parameters is observed.…”

“…Glucocorticoid hormones play an important role in this regulation. There are much more than a hundred sources in the Medline database which have clearly proved that glucocorticoids have a strong oppressive influence on proliferative processes in the esophagus, stomach, different parts of the intestine and liver, and can lead to ulcer formation in the stomach and duodenum [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18]. At present, the situation with glucocorticoid action on proliferation in the digestive system is generally accepted.…”

Identification of Paneth cells in pyloric glands associated with gastric and intestinal mixed-type intestinal metaplasia of the human stomach

“…Since epithelial cell differentiation and migration of gastric glands is thought to be closely linked, the reason why only the former is disturbed is not clear. Recently, epithelial-mesenchymal interactions have attracted attention due to an alteration in miscellaneous conditions and their role in organogenesis [8,9,12]. The question of whether the organization of an IM lesion might be influenced by interstitial cells clearly warrants further study.…”

Morphologic and functional development of whole human fetal stomachs grafted into nude mice

“…Despite the absence of the placenta and therefore of its secretions and its function as a barrier between the host and the fetal organ, the transplanted human embryonic stomachs developed normally in the adult nude mice. The normal‐like differentiation of the grafted human stomach suggests that the host organism may mimic the normal fetal environment and that some factors (such as glucocorticoids, insulin, other hormones and epithelial growth factor) produced by the fetus and the placenta can be substituted by those of the adult mouse (Ichinose et al 1997). Normal differentiation of epithelial, mesenchymal and neurectodermic cells of the graft, as well as an absence of dysplasia during its period of growth, and an absence of abnormal cellular renewal were observed over more than 9 months of fetal stomach tissue growth in nude mice.…”