119 A SHORT PERICONCEPTIONAL MATERNAL HYPERGLYCEMIA IS SUFFICIENT TO DISRUPT THE FETO-PLACENTAL PHENOTYPE IN A RABBIT MODEL

2015 ◽  
Vol 27 (1) ◽  
pp. 151
Author(s):  
D. Rousseau-Ralliard ◽  
A. Tarrade ◽  
R. Thieme ◽  
R. Brat ◽  
MC Aubrière ◽  
...  
Keyword(s):  
Fetal Liver ◽  
Rabbit Model ◽  
Principal Component ◽  
Maternal Diabetes ◽  
Volume Density ◽  
High Plasma ◽  
Lipid Profiles ◽  
Fatty Acid Signature ◽  
Fetal Plasma ◽  
Periconceptional Period

Pre-gestational type 1-diabetes (T1D) increases the risk of miscarriage and congenital malformations and programs the offspring to develop metabolic syndrome in adulthood. Management of maternal diabetes is essential during gestation but could be also highly important around the time of conception. Using a rabbit model, the effects of maternal T1D during the periconceptional period on pre-implantation blastocysts have been well documented, but the effects on feto-placental phenotype at 28 dpc (term = 31 days) has not been explored. Diabetes was induced by Alloxan in dams 7 days before mating. Glycemia was maintained at 15 to 20 mmol L–1 with exogenous insulin injections. At 4 dpc, embryos were collected and transferred into nondiabetic recipients. At 28 dpc, control (C) and diabetic (D) fetuses were collected for biometric records, placental analyses including stereology and gene expression, and lipid profiles of feto-placental tissues by gas chromatography. Lipid data were analysed by principal component analysis. D-fetuses were growth retarded, hyperglycemic, and dyslipidemic compared with C fetuses. Moreover, placental efficiency was much higher in D- than in C-fetuses. The volume density of fetal vessels was significantly decreased in D-placentas compared to C-placentas, whereas the volume density of trophoblast tended to increase (P = 0.051). This morphometric disruption was associated with a deregulation of the expression of genes related to nutrient supply and lipid metabolism. In fetal plasma, a specific fatty acid signature was observed in D- and C-groups. Moreover, the composition of placental and fetal liver membranes differed according to maternal status and fetal sex. Tissues from D-fetuses contained significantly more n-6 polyunsaturated fatty acids compared with C. Docosahexaenoic acid decreased whereas linoleic acid increased in the cardiac membranes of D-fetuses, indicating a higher risk of ischemia. This study demonstrates that exposure to high plasma glucose during the short periconceptional period is sufficient to adversely program fetal phenotype by reducing fetal growth, altering placental function and lipid profiles in all fetal tissues.

scholarly journals Importance of Windows of Exposure to Maternal High-Fat Diet and Feto-Placental Effects: Discrimination Between Pre-conception and Gestational Periods in a Rabbit Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Delphine Rousseau-Ralliard ◽  
Marie-Christine Aubrière ◽  
Nathalie Daniel ◽  
Michèle Dahirel ◽  
Gwendoline Morin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Retardation ◽  
Fetal Liver ◽  
Maternal Diet ◽  
Rabbit Model ◽  
Pairwise Comparison ◽  
Principal Component ◽  
High Fat ◽  
Placental Development ◽  
Fetal Biometry

Context and Aim: Lipid overnutrition in female rabbits, from prepuberty, leads to impaired metabolism (dyslipidemia and increased adiposity) and follicular atresia, and, when continued during gestation, affects offspring phenotype with intrauterine growth retardation (IUGR) and leads to placental and lipid metabolism abnormalities. Growth retardation is already observed in embryo stage, indicating a possible implication of periconceptional exposure. The objective of this study was to discriminate the effects of preconception and gestational exposures on feto-placental development.Materials and Methods: Rabbit 1-day zygotes were collected from female donors under control (CD) or high-fat-high-cholesterol (HD) diet and surgically transferred to the left and right uterus, respectively, of each H (n = 6) or C (n = 7) synchronized recipients. Close to term, four combinations, CC (n = 10), CH (n = 13), HC (n = 13), and HH (n = 6), of feto-placental units were collected, for biometry analyses. Fatty acid (FA) profiles were determined in placental labyrinth, decidua, fetal plasma, and fetal liver by gas chromatography and explored further by principal component analysis (PCA). Candidate gene expression was also analyzed by RT-qPCR in the placenta and fetal liver. Data were analyzed by Kruskal–Wallis followed by Dunn’s pairwise comparison test. Combinations of different data sets were combined and explored by multifactorial analysis (MFA).Results: Compared to controls, HH fetuses were hypotrophic with reduced placental efficiency and altered organogenesis, CH presented heavier placenta but less efficient, whereas HC presented a normal biometry. However, the MFA resulted in a good separation of the four groups, discriminating the effects of each period of exposure. HD during gestation led to reduced gene expression (nutrient transport and metabolism) and big changes in FA profiles in both tissues with increased membrane linoleic acid, lipid storage, and polyunsaturated-to-saturated FA ratios. Pre-conception exposure had a major effect on fetal biometry and organogenesis in HH, with specific changes in FA profiles (increased MUFAs and decreased LCPUFAs).Conclusion: Embryo origin left traces in end-gestation feto-placental unit; however, maternal diet during gestation played a major role, either negative (HD) or positive (control). Thus, an H embryo developed favorably when transferred to a C recipient (HC) with normal biometry at term, despite disturbed and altered FA profiles.

scholarly journals An enriched biosignature of gut microbiota-dependent metabolites characterizes maternal plasma in a mouse model of fetal alcohol spectrum disorder

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Manjot S. Virdee ◽  
Nipun Saini ◽  
Colin D. Kay ◽  
Andrew P. Neilson ◽  
Sze Ting Cecilia Kwan ◽  
...  
Keyword(s):  
Phenolic Acids ◽  
Fetal Liver ◽  
Prenatal Alcohol Exposure ◽  
Fetal Brain ◽  
Principal Component ◽  
Alcohol Exposure ◽  
Maternal Plasma ◽  
Cognitive Disability ◽  
Fetal Alcohol ◽  
Network Analyses

AbstractPrenatal alcohol exposure (PAE) causes permanent cognitive disability. The enteric microbiome generates microbial-dependent products (MDPs) that may contribute to disorders including autism, depression, and anxiety; it is unknown whether similar alterations occur in PAE. Using a mouse PAE model, we performed untargeted metabolome analyses upon the maternal–fetal dyad at gestational day 17.5. Hierarchical clustering by principal component analysis and Pearson’s correlation of maternal plasma (813 metabolites) both identified MDPs as significant predictors for PAE. The majority were phenolic acids enriched in PAE. Correlational network analyses revealed that alcohol altered plasma MDP-metabolite relationships, and alcohol-exposed maternal plasma was characterized by a subnetwork dominated by phenolic acids. Twenty-nine MDPs were detected in fetal liver and sixteen in fetal brain, where their impact is unknown. Several of these, including 4-ethylphenylsulfate, oxindole, indolepropionate, p-cresol sulfate, catechol sulfate, and salicylate, are implicated in other neurological disorders. We conclude that MDPs constitute a characteristic biosignature that distinguishes PAE. These MDPs are abundant in human plasma, where they influence physiology and disease. Their altered abundance here may reflect alcohol’s known effects on microbiota composition and gut permeability. We propose that the maternal microbiome and its MDPs are a previously unrecognized influence upon the pathologies that typify PAE.

Effects of Maternal Diabetes on Fetal Expression of Insulin-Like Growth Factor and Insulin-Like Growth Factor Binding Protein MRNAs in the Rat

1995 ◽  
Vol 147 (2) ◽  
pp. R5-R8 ◽  
Author(s):  
Randal D. Streck ◽  
Veeraramani S. Rajaratnam ◽  
Renata B. Fishman ◽  
Peggy J. Webb
Keyword(s):  
Growth Factor ◽  
Mrna Expression ◽  
Fetal Growth ◽  
Fetal Liver ◽  
Expression Patterns ◽  
Maternal Diabetes ◽  
Limb Bud ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Increased Risk

ABSTRACT Matemal diabetes is associated in humans and rats with an increased risk for fetal growth abnormalities and malformations. Therefore, the effect of maternal diabetes on expression of genes that regulate fetal growth and differentiation is of considerable interest. Developmental growth is regulated in part by the expression and availability of insulin-like growth factors (IGFs). Postnatal expression of a subset of the IGFs and IGF binding proteins (IGFBPs) has been demonstrated to be regulated in response to diabetes and other metabolic conditions. We used in situ hybridization to analyze the effect of maternal diabetes, induced by streptozotocin (STZ) prior to mating, upon prenatal rat IGF and IGFBP mRNA expression. At gestational day (GD) 14, the most striking effect of maternal diabetes on fetal IGF/IGFBP gene expression was a marked increase in the abundance of IGFBP-1 mRNA within the liver primordia of fetuses isolated from diabetic dams compared to age-matched controls. This upregulation cannot be entirely due to the approximately one-half-day delay in fetal development (based on limb bud staging) associated with maternal diabetes, as there was no gross difference in the level of IGFBP-1 mRNA between GD13 and GD14 control fetal livers. In contrast, the fetal mRNA expression patterns of IGF-I, IGF-II and IGFBP-2, -3, -4, -5 and -6 were not grossly altered by maternal diabetes. These data are consistent with the hypothesis that IGFBP-1 produced within the fetal liver and secreted into fetal circulation may play a role in regulating rat fetal growth.

scholarly journals Coordinated changes in hepatic amino acid metabolism and endocrine signals support hepatic glucose production during fetal hypoglycemia

2015 ◽  
Vol 308 (4) ◽  
pp. E306-E314 ◽  
Author(s):  
Satya S. Houin ◽  
Paul J. Rozance ◽  
Laura D. Brown ◽  
William W. Hay ◽  
Randall B. Wilkening ◽  
...  
Keyword(s):  
Fetal Liver ◽  
Hepatic Glucose Production ◽  
Plasma Concentrations ◽  
Glucose Production ◽  
Late Gestation ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Hepatic Glucose ◽  
Molar Percent ◽  
Glucose Output

Reduced fetal glucose supply, induced experimentally or as a result of placental insufficiency, produces an early activation of fetal glucose production. The mechanisms and substrates used to fuel this increased glucose production rate remain unknown. We hypothesized that in response to hypoglycemia, induced experimentally with maternal insulin infusion, the fetal liver would increase uptake of lactate and amino acids (AA), which would combine with hormonal signals to support hepatic glucose production. To test this hypothesis, metabolic studies were done in six late gestation fetal sheep to measure hepatic glucose and substrate flux before (basal) and after [days (d)1 and 4] the start of hypoglycemia. Maternal and fetal glucose concentrations decreased by 50% on d1 and d4 ( P < 0.05). The liver transitioned from net glucose uptake (basal, 5.1 ± 1.5 μmol/min) to output by d4 (2.8 ± 1.4 μmol/min; P < 0.05 vs. basal). The [U-13C]glucose tracer molar percent excess ratio across the liver decreased over the same period (basal: 0.98 ± 0.01, vs. d4: 0.89 ± 0.01, P < 0.05). Total hepatic AA uptake, but not lactate or pyruvate uptake, increased by threefold on d1 ( P < 0.05) and remained elevated throughout the study. This AA uptake was driven largely by decreased glutamate output and increased glycine uptake. Fetal plasma concentrations of insulin were 50% lower, while cortisol and glucagon concentrations increased 56 and 86% during hypoglycemia ( P < 0.05 for basal vs. d4). Thus increased hepatic AA uptake, rather than pyruvate or lactate uptake, and decreased fetal plasma insulin and increased cortisol and glucagon concentrations occur simultaneously with increased fetal hepatic glucose output in response to fetal hypoglycemia.

Rebound increase in fetal breathing movements after 24-h prostaglandin E2 infusion in fetal sheep

1996 ◽  
Vol 80 (1) ◽  
pp. 166-175 ◽  
Author(s):  
S. A. Hollingworth ◽  
S. A. Jones ◽  
S. L. Adamson
Keyword(s):  
Prostaglandin E2 ◽  
Plasma Concentrations ◽  
Treated Group ◽  
High Plasma ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Pge2 Concentration ◽  
Fetal Breathing ◽  
Fetal Breathing Movements ◽  
Rebound Increase

We investigated the hypothesis that the precipitous decrease in prostaglandin E2 (PGE2), a potent inhibitor of fetal breathing, from high plasma concentrations during labor causes a rebound stimulation of breathing without newborn concentrations falling below prelabor fetal values. Fetal plasma PGE2 concentration was gradually increased from 384 +/- 82 (SE) pg/ml in 2-h steps [0 (baseline), 1.5, 3, and 6 micrograms/min] to labor levels (1,230 +/- 381 pg/ml at 6 micrograms/min) and then was maintained for 24 h (n = 9). PGE2 at 1.5 micrograms/min significantly decreased breathing incidence [from 42 +/- 4 (baseline) to 14 +/- 4%] and breath amplitude (from 2.1 +/- 0.5 to 1.5 +/- 0.2 arbitrary units) and increased breath-to-breath interval (from 1.16 +/- 0.07 to 1.56 +/- 0.06 s). No further dose-related changes were observed. During the first 2 h after PGE2 infusion was stopped, PGE2 concentration returned to basal (352 +/- 64 pg/ml) but breathing incidence and amplitude were significantly higher (74 +/- 8% and 2.4 +/- 0.3 arbitrary units, respectively) and breath-to-breath interval was significantly lower (0.95 +/- 0.10 s) than were basal levels. Changes arose within approximately 15 min and were maintained for at least 4 h. Breathing did not change significantly in the saline-treated group (n = 7). Results suggest that the rapid decrease in plasma PGE2 concentration at birth promotes the onset of breathing.

scholarly journals The GH/IGF-I axis in the brushtail possum (Trichosurus vulpecula) pouch young

2003 ◽  
Vol 176 (2) ◽  
pp. 219-225 ◽  
Author(s):  
MC Saunders ◽  
RT Gemmell ◽  
JD Curlewis
Keyword(s):  
Mrna Expression ◽  
Fetal Liver ◽  
Post Partum ◽  
Fold Increase ◽  
High Plasma ◽  
Brushtail Possum ◽  
Trichosurus Vulpecula ◽  
Igf I ◽  
Plasma Gh ◽  
Igfbp 3

Plasma and pituitary GH concentrations and liver GH receptor (GHR), IGF-I and IGF-binding protein-3 (IGFBP-3) mRNA expression were determined in brushtail possum (Trichosurus vulpecula) pouch young aged 12-150 days post-partum and in adults. Mean plasma GH concentrations were highest, measuring around 150 ng/ml, from 12 to 100 days post-partum, and thereafter declined so that by 150 days post-partum levels were not significantly different from those in adults (10.8+/-1.8 ng/ml (S.E.M.)). In contrast to plasma levels, pituitary GH content increased markedly throughout pouch life, with an 87-fold increase between 12 and 150 days post-partum. However, when expressed per gram body weight, pituitary content was relatively constant between 25 and 150 days post-partum, indicating that the decline in plasma GH after 100 days post-partum was not due to decreased synthesis and/or storage of GH in the pituitary gland. Expression of GHR, IGF-I and IGFBP-3 mRNAs was determined by semi-quantitative RT-PCR. Liver GHR and IGF-I mRNA expression were low at 12 and 25 days post-partum and did not show sustained and significant increases (P<0.05) until 125 and 150 days post-partum. IGFBP-3 expression was also low at 12 days post-partum but then increased rapidly to a maximum at 50 days post-partum and thereafter declined. For all three mRNAs, liver expression at day 150 was not significantly different from that in adults. These patterns of gene expression for GHR and IGF-I suggest that the possum liver is resistant to the high plasma GH concentrations during early pouch life and in this way is similar to the fetal liver of some eutherian mammals.

Dietary rumen-protected arginine and N-carbamylglutamate supplementation enhances fetal growth in underfed ewes

2018 ◽  
Vol 30 (8) ◽  
pp. 1116 ◽  
Author(s):  
Lingwei Sun ◽  
Hao Zhang ◽  
Ziyu Wang ◽  
Yixuan Fan ◽  
Yixuan Guo ◽  
...  
Keyword(s):  
Amino Acids ◽  
Fetal Growth ◽  
Fetal Liver ◽  
Plasma Concentrations ◽  
Longissimus Dorsi ◽  
Somatotropic Axis ◽  
Longissimus Dorsi Muscle ◽  
Fetal Plasma ◽  
Dorsi Muscle ◽  
Pregnant Sheep

The present study was conducted with an ovine intrauterine growth restriction (IUGR) model to test the hypothesis that dietary rumen-protected l-arginine (RP-Arg) or N-carbamylglutamate (NCG) supplementation in underfed ewes is effective in enhancing fetal growth. Between Days 35 and 110 of pregnancy, 32 multiparous ewes carrying two fetuses were randomly assigned to one of four groups: a control (CG) group (n = 8; 100% National Research Council (NRC) requirements for pregnant sheep), a nutrient-restricted (RG) group (n = 8; fed 50% NRC requirements, and two treatment (ARG and NCG) groups (n = 8 in each group; fed 50% NRC requirements supplemented with 20 g day−1 RP-Arg or 5 g day−1 NCG. All ewes were killed on Day 110 of pregnancy to determine fetal weight and fetal organ weights, and metabolites and hormones in fetal plasma, amino acid concentrations in the fetal liver and longissimus dorsi muscle, and expression of mRNAs in the somatotropic axis. Maternal and fetal bodyweight and the weight of most fetal organs expressed as a percentage of bodyweight increased in response to ARG and NCG compared with values for fetuses from RG ewes. Fetal plasma concentrations of insulin, insulin-like growth factor 1, total amino acids, lactate, thyroxine, and the thyroxine/tri-iodothyronine ratio were lower in fetuses from RG ewes compared with the other treatment groups, but concentrations of growth hormone, non-esterified fatty acids, and total cholesterol were greater in fetuses from RG ewes. Maternal RP-Arg or NCG supplementation increased concentrations of amino acids in fetal tissues and expression of mRNAs for somatotropic axis proteins in fetuses from RG ewes. These findings suggest that maternal RP-Arg and NCG supplementation of underfed ewes decreases fetal IUGR by improving metabolic homeostasis of fetal endocrinology, increasing the availability of amino acids in the fetal liver and longissimus dorsi muscle and affecting the expression of somatotropic axis genes.

scholarly journals Isocaloric maternal low-protein diet alters IGF-I, IGFBPs, and hepatocyte proliferation in the fetal rat

2003 ◽  
Vol 285 (5) ◽  
pp. E991-E1000 ◽  
Author(s):  
Ilham El Khattabi ◽  
Francine Grégoire ◽  
Claude Remacle ◽  
Brigitte Reusens
Keyword(s):  
Cell Proliferation ◽  
Fetal Liver ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Hepatocyte Proliferation ◽  
Liver Growth ◽  
Fetal Plasma ◽  
Low Protein ◽  
Igf I

We investigated the effect of an isocaloric maternal low-protein diet during pregnancy in rats on the proliferative capacity of cultured fetal hepatocytes. The potential roles of these changes on the IGF-IGF-binding protein (IGFBP) axis, and the role of insulin and glucocorticoids in liver growth retardation, were also evaluated. Pregnant Wistar rats were fed a control (C) diet (20% protein) or a low-protein (LP) diet (8%) throughout gestation. In primary culture, the DNA synthesis of hepatocytes derived from LP fetuses was decreased by ∼30% compared with control hepatocytes ( P < 0.05). In parallel, in vivo moderate protein restriction in the dam reduced the fetal liver weight and IGF-I level in fetal plasma ( P < 0.01) and augmented the abundance of 29- to 32-kDa IGFBPs in fetal plasma ( P < 0.01) and fetal liver ( P < 0.01). By contrast, the abundance of IGF-II mRNA in liver of LP fetuses was unaffected by the LP diet. In vitro, the LP-derived hepatocytes produced less IGF-I ( P < 0.01) and more 29- to 32-kDa IGFBPs ( P < 0.01) than hepatocytes derived from control fetuses. These alterations still appeared after 3–4 days of culture, indicating some persistence in programming. Dexamethasone treatment of control-derived hepatocytes decreased cell proliferation (54 ± 2.3%, P < 0.01) and stimulated 29- to 32-kDa IGFBPs, whereas insulin promoted fetal hepatocyte growth (127 ± 5.5%, P < 0.01) and inhibited 29- to 32-kDa IGFBPs. These results show that liver growth and cell proliferation in association with IGF-I and IGFBP levels are affected in utero by fetal undernutrition. It also suggests that glucocorticoids and insulin may modulate these effects.

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