Real supermodels wear wool: summarizing the impact of the pregnant sheep as an animal model for adaptive fetal programming

Beede, Kristin A; Limesand, Sean W.; Petersen, Jessica L.; Yates, Dustin T

doi:10.1093/af/vfz018

Cited by 29 publications

(28 citation statements)

References 45 publications

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“…This congestion not only caused less opportunity for each embryo to find a space for its growth and development but it also resulted in higher stillborn lambs, mummified embryos, and even produced lower birth weight lambs. Recently, Beede et al [28] recognized various factors, including heat stress within the multiple-bearing uteri in sheep resulting in the incidence of intrauterine growth restriction. As twin birth weight increased, there found a decrease in the mortalities between birth and weaning [29].…”

Section: Discussionmentioning

confidence: 99%

Consequences of twinning induction to Noemi ewes by a recombinant human follicle-stimulating hormone compared with pituitary-derived porcine follicle-stimulating hormone on follicular dynamics, maternal biochemical attributes, and neonatal traits

et al. 2020

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Aim: The aim of this study was to investigate the effectiveness of using recombinant human follicle-stimulating hormone (FSH) compared with pituitary-derived porcine FSH given as one dose or multiple doses on the neonatal traits, follicular dynamics, and maternal blood biochemical constituents in Noemi ewes. Materials and Methods: A 3×2 factorial arrangement was designed utilizing 60 adults Noemi ewes to test the effects of using two sources of FSH (human vs. porcine) in addition to control, either given as a single total dose or six descending doses to provoke twinning. Six treatments (T) were tested (n=10 ewes/T). C1 and C6 served as control ewes given saline as one dose and six doses, respectively; H1 and H6 ewes were given human FSH as one and six doses; and P1 and P6 ewes were given porcine FSH similar to the above treatments. Saline and/or FSH administration were administered at days 8, 9, and 10 of the 10-day controlled internal drug release (CIDR) implant. At CIDR removal, fertile rams were used for natural mating. Blood samples for the assessment of serum metabolites were collected. Results: Twinning increased in FSH-treated ewes than control. However, giving FSH of either source as a single dose resulted in a higher incidence of stillbirths. Pregnancy rates were 30, 40, 50, 60, 70, and 80% in C1, C6, P1, P6, H1, and H6, respectively. Respective percent of ewes delivering twins/multiple birth was 0, 0, 80, 66.7, 71.4, and 87.5%. FSH of human source was more efficient for folliculogenesis than porcine FSH. Administration of FSH increased blood cholesterol, decreased high-density lipoprotein; however, low-density lipoprotein levels were not different than control. Moreover, an interaction (p<0.05) exists between source and type of FSH administration on blood glucose. Six doses of FSH elevated blood protein. Blood albumin decreased by porcine-FSH but not affected by human-FSH. Blood globulins were not different due to source of FSH, whereas giving FSH as six doses increased globulins than in single-dose protocol. Contrariwise, an interaction was found between source and type of FSH administration on elevating the activity of alanine aminotransferase and reducing the activity of aspartate aminotransferase. Conclusion: Administration of human FSH at 180 IU in six descending doses resulted in the best neonatal outcomes and maternal health in Noemi ewes.

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Section: Discussionmentioning

confidence: 99%

Consequences of twinning induction to Noemi ewes by a recombinant human follicle-stimulating hormone compared with pituitary-derived porcine follicle-stimulating hormone on follicular dynamics, maternal biochemical attributes, and neonatal traits

et al. 2020

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“…Studies of the effect of IUGR on fat deposition in later life have largely been performed on rodent models, which have limitations due to the maturation of most organs occurring after, rather than around the time of birth as well as different BAT deposits and metabolism in rodent foetuses and newborns compared to humans [27, 35, 36]. For this reason, we utilised a sheep model, which reflects human pregnancy in terms of the prenatal timing of foetal development, and the non‐shivering thermogenesis response after birth [16, 37].…”

Section: Introductionmentioning

confidence: 99%

In utero substrate restriction by placental insufficiency or maternal undernutrition decreases optical redox ratio in foetal perirenal fat

Łaźniewska

Darby

Holman

et al. 2021

Journal of Biophotonics

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Intrauterine growth restriction (IUGR) can result from reduced delivery of substrates, including oxygen and glucose, during pregnancy and may be caused by either placental insufficiency or maternal undernutrition. As a consequence of IUGR, there is altered programming of adipose tissue and this can be associated with metabolic diseases later in life. We have utilised two sheep models of IUGR, placental restriction and late gestation undernutrition, to determine the metabolic effects of growth restriction on foetal perirenal adipose tissue (PAT). Two‐photon microscopy was employed to obtain an optical redox ratio, which gives an indication of cell metabolism. PAT of IUGR foetuses exhibited higher metabolic activity, altered lipid droplet morphology, upregulation of cytochrome c oxidase subunit genes and decreased expression of genes involved in growth and differentiation. Our results indicate that there are adaptations in PAT of IUGR foetuses that might be protective and ensure survival in response to an IUGR insult.

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“…The resulting vasoconstriction reduces uteroplacental blood ow and limits fetal growth (6). Sheep are utilized as a model for placental insu ciency and IUGR in humans due to similarities in placental structure and parallel IUGR pathologies after birth and into adulthood (24)(25)(26)(27). Proper placental vascularization and function depends on the nely tuned regulation of gene expression throughout gestation (28).…”

Section: Introductionmentioning

confidence: 99%

Differentially expressed genes in cotyledon of ewes fed mycotoxins

Britt

Noorai

Duckett

2020

Preprint

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Background Ergot alkaloids (E+) are mycotoxins produced by the endophytic fungus, Epichloë coenophiala, in tall fescue that are associated with ergotism in animals. Exposure to ergot alkaloids during gestation reduces fetal weight and placental mass in sheep. These reductions are related to vasoconstrictive effects of ergot alkaloids and potential alterations in nutrient transport to the fetus. Cotyledon samples were obtained from eight ewes that were fed E+ (n = 4; E+/E+) or E- (endophyte-free without ergot alkaloids; n = 4; E-/E-) seed during both mid (d 35 to 85) and late (d 85-133) gestation to assess differentially expressed genes associated with ergot alkaloid induced reductions in placental mass and fetal weight, and discover potential adaptive mechanisms to alter nutrient supply to fetus. Results Ewes fed E+/E+ fescue seed during both mid and late gestation had 20% reduction in fetal body weight and 33% reduction in cotyledon mass compared to controls (E-/E-). Over 13,000 genes were identified with 110 upregulated and 33 downregulated. Four genes had a |log2FC|>5 for ewes consuming E+/E+ treatment compared to controls: LECT2, SLC22A9, APOC3, and MBL2. REViGO revealed clusters of upregulated genes associated glucose, carbohydrates, lipid, protein, macromolecular and cellular metabolism, regulation of wound healing and response to starvation. For downregulated genes, no clusters were present, but all enriched GO terms were associated with anion and monocarboxylic acid transport. The complement and coagulation cascade and the peroxisome proliferator-activated receptor signaling pathway were found to be enriched for ewes consuming E+/E+ treatment. Conclusions Consumption of ergot alkaloids during gestation altered the cotyledonary transcriptome specifically related to macronutrient metabolism, wound healing and starvation. These results show that ergot alkaloid exposure upregulates genes involved in nutrient metabolism to supply the fetus with additional substrates in attempts to rescue fetal growth.

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Real supermodels wear wool: summarizing the impact of the pregnant sheep as an animal model for adaptive fetal programming

Cited by 29 publications

References 45 publications

Consequences of twinning induction to Noemi ewes by a recombinant human follicle-stimulating hormone compared with pituitary-derived porcine follicle-stimulating hormone on follicular dynamics, maternal biochemical attributes, and neonatal traits

Consequences of twinning induction to Noemi ewes by a recombinant human follicle-stimulating hormone compared with pituitary-derived porcine follicle-stimulating hormone on follicular dynamics, maternal biochemical attributes, and neonatal traits

In utero substrate restriction by placental insufficiency or maternal undernutrition decreases optical redox ratio in foetal perirenal fat

Differentially expressed genes in cotyledon of ewes fed mycotoxins

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