Barbiturate euthanasia solution‐induced tissue artifact in nonhuman primates

Grieves, Jessica; Dick, Edward J.; Schlabritz-loutsevich, N. E.; Butler, Steve; Leland, M. Michelle; Price, Stuart E.; Schmidt, Christa; Nathanielsz, Peter W.; Hubbard, Gene B.

doi:10.1111/j.1600-0684.2007.00271.x

Cited by 44 publications

(21 citation statements)

References 11 publications

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“…This method is approved by the American Veterinary Medical Association. We have demonstrated fewer tissue artifacts following exsanguination than following administration of euthanasia solutions, which produce marked histological changes, especially in the liver (Grieves et al 2008). The placenta and fetus were removed from the uterus and immediately submitted for morphometric measurements including fetal and liver weight, complete pathological evaluation, and tissue sampling.…”

Section: Methodsmentioning

confidence: 93%

Epigenetic modification of fetal baboon hepatic phosphoenolpyruvate carboxykinase following exposure to moderately reduced nutrient availability

Nijland

Mitsuya

et al. 2010

The Journal of Physiology

110

109

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Decreased maternal nutrient availability during pregnancy induces compensatory fetal metabolic and endocrine responses. Knowledge of cellular changes involved is critical to understanding normal and abnormal development. Several studies in rodents and sheep report increased fetal plasma cortisol and associated increased gluconeogenesis in response to maternal nutrient reduction (MNR) but observations in primates are lacking. We determined MNR effects on fetal liver phosphoenolpyruvate carboxykinase 1 (protein, PEPCK1; gene, PCK1 orthologous/homologous human chromosomal region 20q13.31) at 0.9 gestation (G). Female baboon social groups were fed ad libitum (control, CTR) or 70% CTR (MNR) from 0.16 to 0.9G when fetuses were delivered by caesarean section under general anaesthesia. Plasma cortisol was elevated in fetuses of MNR mothers (P < 0.05). Immunoreactive PEPCK1 protein was located around the liver lobule central vein and was low in CTR fetuses but rose to 63% of adult levels in MNR fetuses. PCK1 mRNA measured by QRT-PCR increased in MNR (2.3-fold; P < 0.05) while the 25% rise in protein by Western blot analysis was not significant. PCK1 promoter methylation analysis using bisulfite sequencing was significantly reduced in six out of nine CpG-dinucleotides evaluated in MNR compared with CTR liver samples. In conclusion, these are the first data from a fetal non-human primate indicating hypomethylation of the PCK1 promoter in the liver following moderate maternal nutrient reduction.

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Section: Methodsmentioning

confidence: 93%

Epigenetic modification of fetal baboon hepatic phosphoenolpyruvate carboxykinase following exposure to moderately reduced nutrient availability

Nijland

Mitsuya

et al. 2010

The Journal of Physiology

110

109

View full text Add to dashboard Cite

show abstract

“…This change has been made since we have demonstrated fewer tissue artefacts following exsanguination than following administration of euthanasia solutions, which produce marked histological changes, especially in the liver (Grieves et al . ). Morphometric measurements were collected and tissue samples obtained immediately after the placenta and fetus were removed from the uterus.…”

Section: Methodsmentioning

confidence: 97%

Primate fetal hepatic responses to maternal obesity: epigenetic signalling pathways and lipid accumulation

Puppala

Glenn

et al. 2018

The Journal of Physiology

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Maternal obesity (MO) increases offspring cardiometabolic disease risk. Altered fetal liver development in response to the challenge of MO has metabolic consequences underlying adverse offspring life-course health outcomes. Little is known about the molecular pathways and potential epigenetic changes regulating primate fetal liver responses to MO. We hypothesized that MO would induce fetal baboon liver epigenetic changes resulting in dysregulation of key metabolic pathways that impact lipid metabolism. MO was induced prior to pregnancy by a high-fat, high-fructose diet. Unbiased gene and microRNA (small RNA Seq) abundance analyses were performed on fetal baboon livers at 0.9 gestation and subjected to pathway analyses to identify fetal liver molecular responses to MO. Fetal baboon liver lipid and glycogen content were quantified by the Computer Assisted Stereology Toolbox. In response to MO, fetal livers revealed dysregulation of TCA cycle, proteasome, oxidative phosphorylation, glycolysis and Wnt/β-catenin signalling pathways together with marked lipid accumulation supporting our hypothesis that multiple pathway dysregulation detrimentally impacts lipid management. This is the first study of MO programming of the non-human primate fetal liver using unbiased transcriptome analysis to detect changes in hepatic gene expression levels and identify potential microRNA epigenetic regulators of metabolic disruption.

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“…This method is approved by the American Veterinary Medical Association. Previous study has demonstrated fewer tissue artifacts after exsanguination than after administration of euthanasia solutions (33). Maternal and fetal blood was collected from the femoral artery and umbilical vein, respectively.…”

Section: Methodsmentioning

confidence: 99%

Sexually Dimorphic Effects of Maternal Nutrient Reduction on Expression of Genes Regulating Cortisol Metabolism in Fetal Baboon Adipose and Liver Tissues

Guo

Myatt

et al. 2013

Diabetes

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Maternal nutrient reduction (MNR) during fetal development may predispose offspring to chronic disease later in life. Increased regeneration of active glucocorticoids by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in metabolic tissues is fundamental to the developmental programming of metabolic syndrome, but underlying mechanisms are unknown. Hexose-6-phosphate dehydrogenase (H6PD) generates NADPH, the cofactor for 11β-HSD1 reductase activity. CCAAT/enhancer binding proteins (C/EBPs) and the glucocorticoid receptor (GR) regulate 11β-HSD1 expression. We hypothesize that MNR increases expression of fetal C/EBPs, GR, and H6PD, thereby increasing expression of 11β-HSD1 and reductase activity in fetal liver and adipose tissues. Pregnant MNR baboons ate 70% of what controls ate from 0.16 to 0.9 gestation (term, 184 days). Cortisol levels in maternal and fetal circulations increased in MNR pregnancies at 0.9 gestation. MNR increased expression of 11β-HSD1; H6PD; C/EBPα, -β, -γ; and GR in female but not male perirenal adipose tissue and in male but not female liver at 0.9 gestation. Local cortisol level and its targets PEPCK1 and PPARγ increased correspondingly in adipose and liver tissues. C/EBPα and GR were found to be bound to the 11β-HSD1 promoter. In conclusion, sex- and tissue-specific increases of 11β-HSD1, H6PD, GR, and C/EBPs may contribute to sexual dimorphism in the programming of exaggerated cortisol regeneration in liver and adipose tissues and offsprings’ susceptibility to metabolic syndrome.

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Barbiturate euthanasia solution‐induced tissue artifact in nonhuman primates

Abstract: When the recommended dose of agent was used, tissue damage was generally reduced, minimal, or undetectable. Barbiturate-induced artifacts in NHPs are essentially the same as in other laboratory species.

Cited by 44 publications

References 11 publications

Epigenetic modification of fetal baboon hepatic phosphoenolpyruvate carboxykinase following exposure to moderately reduced nutrient availability

Epigenetic modification of fetal baboon hepatic phosphoenolpyruvate carboxykinase following exposure to moderately reduced nutrient availability

Primate fetal hepatic responses to maternal obesity: epigenetic signalling pathways and lipid accumulation

Sexually Dimorphic Effects of Maternal Nutrient Reduction on Expression of Genes Regulating Cortisol Metabolism in Fetal Baboon Adipose and Liver Tissues

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