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Association of maternal pancreatic function and foetal growth in rats treated with DFU, a selective cyclooxygenase-2
1Experimental Teratology Unit of the Human Anatomy Department, Medical University of Lublin, Poland. fb3@wp.pl
Abstract:
Constitutive (COX-1) and inducible (COX-2) cyclooxygenase isoforms have been detected in various mammalian tissues. Their activity is blocked by non-steroidal anti-inflammatory drugs that may induce various side reactions. The aim of the study was to evaluate the effects of DFU, a selective COX-2 inhibitor, on exocrine and endocrine pancreatic function and the immunoexpression of both COX isoforms in maternal and foetal rat pancreases. The compound was administered to pregnant Wistar rats once daily from the 8th to the 21st day of gestation. Glucose level and amylase activity were determined in the maternal sera. Maternal and foetal pancreases were examined histologically. Immunoexpression of COX-1 and COX-2 was also evaluated. Both biochemical parameters, as well as the histological structure of the pancreas were undisturbed in the dams and their foetuses. The maternal glucose level was found to be an important factor for foetal growth. Strong cytoplasmic COX-1 immunostaining was observed in acinar secretory cells, whereas in islets the immune reaction was weak. Endocrine cells also revealed strong cytoplasmic COX-2 staining in the maternal and foetal pancreases. Acinar cells exhibited nuclear reaction, which was strong in the foetal but weak in the maternal pancreases. No differences in COX immunoexpression were found between the DFU-exposed and the control groups in either mothers or foetuses. It should be stressed that DFU administered throughout mid and late pregnancy in rats did not change maternal or foetal pancreatic morphology or immunoexpression of either of the main COX isoforms in the organ.
Insights
Selective COX-2 inhibitor DFU did not affect maternal or fetal rat pancreas function or COX isoform expression during pregnancy. Maternal glucose levels were key for fetal growth, but DFU showed no adverse pancreatic effects.
Area of Science:
- Pharmacology
- Developmental Biology
- Gastroenterology
Background:
- Cyclooxygenase (COX) enzymes, COX-1 and COX-2, are present in mammalian tissues.
- Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit COX activity but can cause side effects.
- Selective COX-2 inhibitors are investigated for targeted anti-inflammatory effects.
Purpose of the Study:
- To assess the impact of DFU, a selective COX-2 inhibitor, on pancreatic function (exocrine and endocrine) in pregnant rats.
- To examine the immunoexpression of COX-1 and COX-2 in maternal and fetal rat pancreases following DFU administration.
- To evaluate potential teratogenic effects of DFU on pancreatic morphology.
Main Methods:
- Pregnant Wistar rats received daily DFU from day 8 to 21 of gestation.
- Maternal serum glucose levels and amylase activity were measured.
- Pancreatic tissues from mothers and fetuses were analyzed histologically.
- Immunohistochemistry was used to evaluate COX-1 and COX-2 expression patterns.
Main Results:
- DFU administration did not alter maternal or fetal pancreatic histology or biochemical parameters (glucose, amylase).
- COX-1 showed strong cytoplasmic staining in maternal/fetal acinar cells; COX-2 showed strong cytoplasmic staining in maternal/fetal endocrine cells.
- Acinar cells displayed nuclear COX-2 staining, stronger in fetuses than mothers.
- No significant differences in COX immunoexpression were observed between DFU-exposed and control groups.
Conclusions:
- DFU, a selective COX-2 inhibitor, is safe for maternal and fetal pancreatic morphology and COX isoform expression during rat pregnancy.
- Maternal glucose levels are a critical factor influencing fetal development.
- The study provides evidence against DFU-induced pancreatic toxicity in utero.
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