Effect of sporidesmin-induced liver damage in ewes before mating on growth of the foetus and placenta

Sporidesmin is a fungal toxin commonly found in pasture. It causes liver damage in sheep that resembles cholestasis in humans. We determined whether pre-mating sporidesmin-induced liver damage in ewes might provide a useful approach to the experimental induction of intrauterine growth restriction (IUGR). Romney ewes were drenched with sporidesmin extracts. Affected ewes (SP, n=44) and controls (CN, n=42) were mated. Sporidesmin treatment decreased pregnancy rate (non-pregnant; SP 43% vs. CN 12%, twin; SP 23% vs. CN 52%, both P<0.05). SP foetuses were 6% lighter than CN foetuses at 89 days of gestation, but not at 134 days. Increasing maternal plasma gamma glutamyl transferase activities at mating were associated at 89 days with reduced maternal weight (-1.1: -1.9, -0.3 kg/100 U/l, mean effect size: 95% confidence intervals), increased visual liver damage and reduced placentome number (-1.4: -2.7, -0.1/100 U/l) and foetal pancreatic weight (-21: -38, -4 mg/100 U/l). They were also associated at 134 days with reduced weight of the foetal pancreas (-132: -221, -42 mg/100 U/l), spleen (-139: -231, -47 mg/100 U/l) and thyroid (-29: -48, -10 mg/100 U/l) and decreased A-type placentomes (-3.0: -5.0, -1.0/100 U/l). Pre-mating sporidesmin-induced liver damage is not useful for induction of experimental IUGR but does impair the growth of the foetal pancreas, spleen and thyroid and alter placental morphometry.

Cultured epithelial cells derived from human foetal pancreas as a model for the study of cystic fibrosis: further analyses on the origins and nature of the cell types

The establishment of a tissue-culture system for epithelial cells derived from human foetal pancreas has recently been reported. Further analyses have now been made on these cells in vitro, together with parallel investigation of the distribution of different cell types within the intact foetal pancreas. Results support the view that the cultured cells are ductal in origin and nature. Pancreatic epithelial cell cultures have also been established from foetuses with cystic fibrosis.

Organ culture of human foetal pancreas: conditions which affect basal and stimulated insulin release

Human foetal pancreas has been maintained in organ culture with net synthesis and release of insulin for up to 60 days. The age of the donor foetus affected the basal insulin release rate. A plateau of secretion was reached with foetuses of ≥ 16 weeks of gestation. Explants cultured within 2 h of expulsion following prostaglandin induced termination secreted 3.0 times more insulin after 20 days of culture than those cultured within 2–4 h and 8.1 times more than those cultured more than 4 h post-termination. A high oxygen environment was toxic to the explants during culture. Fresh tissue responded to a high concentration of glucose (19.3 mm) with a small but significant increase in insulin secretion. The addition of 10 mm theophylline caused a major increase in insulin release. Cultured tissue did not respond to glucose alone but did show increased insulin release following stimulation with glucose (22 mm) together with theophylline (10 mm) in static incubation. The culture of human foetal pancreatic tissue may be useful in maintaining responsive beta cells and may help to ensure an adequate amount of donor tissue for future transplantation into diabetic patients.