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 Paradoxical leanness in the imprinting-centre deletion mouse model for Prader–Willi syndrome

2017 ◽  
Vol 232 (1) ◽  
pp. 123-135 ◽  
Author(s):  
David M Golding ◽  
Daniel J Rees ◽  
Jennifer R Davies ◽  
Dinko Relkovic ◽  
Hannah V Furby ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Mouse Model ◽  
Growth Retardation ◽  
Single Gene ◽  
Neurodevelopmental Disorder ◽  
Prader Willi Syndrome ◽  
High Fat ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose

Prader–Willi syndrome (PWS), a neurodevelopmental disorder caused by loss of paternal gene expression from 15q11–q13, is characterised by growth retardation, hyperphagia and obesity. However, as single gene mutation mouse models for this condition display an incomplete spectrum of the PWS phenotype, we have characterised the metabolic impairment in a mouse model for ‘full’ PWS, in which deletion of the imprinting centre (IC) abolishes paternal gene expression from the entire PWS cluster. We show that PWS-ICdel mice displayed postnatal growth retardation, with reduced body weight, hyperghrelinaemia and marked abdominal leanness; proportionate retroperitoneal, epididymal/omental and inguinal white adipose tissue (WAT) weights being reduced by 82%, 84% and 67%, respectively. PWS-ICdel mice also displayed a 48% reduction in proportionate interscapular brown adipose tissue (isBAT) weight with significant ‘beiging’ of abdominal WAT, and a 2°C increase in interscapular surface body temperature. Maintenance of PWS-ICdel mice under thermoneutral conditions (30°C) suppressed the thermogenic activity in PWS-ICdel males, but failed to elevate the abdominal WAT weight, possibly due to a normalisation of caloric intake. Interestingly, PWS-ICdel mice also showed exaggerated food hoarding behaviour with standard and high-fat diets, but despite becoming hyperphagic when switched to a high-fat diet, PWS-ICdel mice failed to gain weight. This evidence indicates that, unlike humans with PWS, loss of paternal gene expression from the PWS cluster in mice results in abdominal leanness. Although reduced subcutaneous insulation may lead to exaggerated heat loss and thermogenesis, abdominal leanness is likely to arise from a reduced lipid storage capacity rather than increased energy utilisation in BAT.

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.

Hox gene expression profiles during embryonic development of common sole

2019 ◽  
Vol 69 (2) ◽  
pp. 183-198
Author(s):  
Menelaos Kavouras ◽  
Emmanouil E. Malandrakis ◽  
Eleni Golomazou ◽  
Ioannis Konstantinidis ◽  
Ewout Blom ◽  
...  
Keyword(s):  
Gene Expression ◽  
Embryonic Development ◽  
First Generation ◽  
Profile Analysis ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Pairwise Comparison ◽  
Principal Component ◽  
Valuable Insight ◽  
Common Sole

Abstract Common sole (Solea solea) aquaculture production is based mostly on wild-caught breeders. Recently, the successful reproduction of first-generation fish that were reared in captivity was accomplished. A consistent good quality and quantity of produced eggs throughout the year, and of next-generation broodstock, is important for reducing the overall cost of production. Hox genes play a pivotal role in normal embryonic development and alterations of their temporal expression level may be important for egg viability. Expression profile analysis of five hox genes (hoxa1a, hoxa2a, hoxa2b, hoxb1a and hoxb1b) involved in early embryonic development and of hoxa13a, which is involved in late stages, was carried out. Results revealed a premature and/or maternal expression of hoxa13a in sole embryos, and the detection of hoxa2a and hoxa2b genes as members of paralog group 2. Principal Component Analysis of hox gene expression in 54 ± 6 hours post fertilization embryos coming from wild-caught broodstock and a first-generation one reared in the hatchery, unveiled that these broodstocks are clearly distinct. In addition, their pairwise comparison revealed significant differences in the expression levels of hoxb1a and hoxb1b genes. Hox gene regulation during embryonic development could give valuable insight into rearing sole broodstocks with different origin in concert, and also into gaining a steady mass production of eggs, either in quality or quantity, all year round.

scholarly journals Developmental origins of disease and determinants of chromatin structure: maternal diet modifies the primate fetal epigenome

2008 ◽  
Vol 41 (2) ◽  
pp. 91-102 ◽  
Author(s):  
Kjersti M Aagaard-Tillery ◽  
Kevin Grove ◽  
Jacalyn Bishop ◽  
Xingrao Ke ◽  
Qi Fu ◽  
...  
Keyword(s):  
Chromatin Structure ◽  
High Fat Diet ◽  
Fetal Liver ◽  
Maternal Diet ◽  
Hepatic Tissue ◽  
High Fat ◽  
Differential Display Pcr ◽  
Covalent Modifications ◽  
H3 Acetylation

Chromatin structure is epigenetically altered via covalent modifications of histones to allow for heritable gene regulation without altering the nucleotide sequence. Multiple lines of evidence from rodents have established a role for epigenetic remodeling in regulating gene transcription in response to an altered gestational milieu. However, to date, it is unknown whether variations in the intrauterine environment in primates similarly induce changes in key determinants of hepatic chromatin structure. We hypothesized that a maternal high-fat diet would alter the epigenomic profile of the developing offspring, which would result in alterations in fetal gene expression. Age- and weight-matched adult female Japanese macaques were placed on control (13% fat) or high-fat (35% fat) breeder diets and mated annually over a 4-year interval. Fetuses in successive years were delivered near term (e130 of 167 days) and underwent necropsy with tissue harvest. Fetal histones were acid extracted for characterization of H3 modification and chromatin immunoprecipitation (ChIP) with differential display PCR; fetal RNA, DNA, and cytoplasmic and nuclear protein extracts were similarly extracted for comparison. Chronic consumption of a maternal high-fat diet results in a threefold increase in fetal liver triglycerides and histologic correlates of non-alcoholic fatty liver disease. These gross changes in the fetal liver are accompanied by a statistically significant hyperacetylation of fetal hepatic tissue at H3K14 (199.85±9.64 vs 88.8±45.4; P=0.038) with a trend towards the increased acetylation at H3K9 (140.9±38.7 vs 46.6±6.53; P=0.097) and at H3K18 (69.0±3.54 vs 58.0±4.04; P=0.096). However, epigenetic modifications on fetal hepatic H3 associated with gene repression were absent or subtle (P>0.05). Subsequent characterization of key epigenetic determinants associated with H3 acetylation marks revealed similar significant alterations in association with a high-fat maternal diet (e.g., relative fetal histone deacetylase 1 (HDAC1) gene expression 0.61±0.25; P=0.011). Consistent with our mRNA expression profile, fetal nuclear extracts from offspring of high-fat diet animals were observed to be significantly relatively deplete of HDAC1 protein (36.07±6.73 vs 83.18±7.51; P=0.006) and in vitro HDAC functional activity (0.252±0.03 vs 0.698±0.02; P<0.001). We employ these observations in ChIP differential display PCR to attempt to identify potential fetal genes whose expression is reprogramed under conditions of a high-fat maternal diet. We quantitatively confirm a minimum of a 40% alteration in the expression of several genes of interest: glutamic pyruvate transaminase (alanine aminotransferase) 2 (GPT2) (1.59±0.23-fold; P=0.08), DNAJA2 (1.36±0.21; P=0.09), and Rdh12 (1.88±0.15; P=0.01) are appreciably increased in fetal hepatic tissue from maternal caloric-dense diet animals when compared with control while Npas2, a peripheral circadian regulator, was significantly downmodulated in the offspring of high-fat diet animals (0.66±0.08; P=0.03). In this study, we show that a current significant in utero exposure (caloric-dense high-fat maternal diet) induces site-specific alterations in fetal hepatic H3 acetylation. Employing ChIP, we extend these observations to link modifications of H3 acetylation with alterations in gene-specific expression. These results suggest that a caloric-dense maternal diet leading to obesity epigenetically alters fetal chromatin structure in primates via covalent modifications of histones and hence lends a molecular basis to the fetal origins of adult disease hypothesis.

scholarly journals A Maternal High Fat Diet Leads to Sex-Specific Programming of Mechanical Properties in Supraspinatus Tendons of Adult Rat Offspring

2021 ◽  
Vol 8 ◽  
Author(s):  
Scott M. Bolam ◽  
Vidit V. Satokar ◽  
Subhajit Konar ◽  
Brendan Coleman ◽  
Andrew Paul Monk ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Fat Diet ◽  
Maternal Diet ◽  
Biomechanical Properties ◽  
Female Offspring ◽  
Male Offspring ◽  
Chow Diet ◽  
Adult Offspring ◽  
High Fat ◽  
The Impact

Background: Over half of women of reproductive age are now overweight or obese. The impact of maternal high-fat diet (HFD) is emerging as an important factor in the development and health of musculoskeletal tissues in offspring, however there is a paucity of evidence examining its effects on tendon. Alterations in the early life environment during critical periods of tendon growth therefore have the potential to influence tendon health that cross the lifespan. We hypothesised that a maternal HFD would alter biomechanical, morphological and gene expression profiles of adult offspring rotator cuff tendon.Materials and Methods: Female Sprague-Dawley rats were randomly assigned to either: control diet (CD; 10% kcal or 43 mg/g from fat) or HFD (45% kcal or 235 mg/g from fat) 14 days prior to mating and throughout pregnancy and lactation. Eight female and male offspring from each maternal diet group were weaned onto a standard chow diet and then culled at postnatal day 100 for tissue collection. Supraspinatus tendons were used for mechanical testing and histological assessment (cellularity, fibre organisation, nuclei shape) and tail tendons were collected for gene expression analysis.Results: A maternal HFD increased the elasticity (Young's Modulus) in the supraspinatus tendon of male offspring. Female offspring tendon biomechanical properties were not affected by maternal HFD. Gene expression of SCX and COL1A1 were reduced in male and female offspring of maternal HFD, respectively. Despite this, tendon histological organisation were similar between maternal diet groups in both sexes.Conclusion: An obesogenic diet during pregnancy increased tendon elasticity in male, but not female, offspring. This is the first study to demonstrate that maternal diet can modulate the biomechanical properties of offspring tendon. A maternal HFD may be an important factor in regulating adult offspring tendon homeostasis that may predispose offspring to developing tendinopathies and adverse tendon outcomes in later life.

Intergenerational effects of a maternal high fat diet on feto-placental development in a rabbit model

Placenta ◽  
2014 ◽  
Vol 35 (9) ◽  
pp. A28
Author(s):  
Anne Tarrade ◽  
Marie-Christine Aubrière ◽  
Delphine Rousseau-Ralliard ◽  
Michèle Dahirel ◽  
Eve Mourier ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Rabbit Model ◽  
High Fat ◽  
Placental Development ◽  
Intergenerational Effects

scholarly journals Maternal curcumin supplementation ameliorates placental function and fetal growth in mice with intrauterine growth retardation†

2020 ◽  
Vol 102 (5) ◽  
pp. 1090-1101 ◽  
Author(s):  
Lina Qi ◽  
Jingle Jiang ◽  
Jingfei Zhang ◽  
Lili Zhang ◽  
Tian Wang
Keyword(s):  
Gene Expression ◽  
Fetal Growth ◽  
Growth Retardation ◽  
Intrauterine Growth Retardation ◽  
Fetal Liver ◽  
Placental Function ◽  
Antioxidant Gene ◽  
Intrauterine Growth ◽  
Antioxidant Gene Expression ◽  
Placental Efficiency

Abstract Intrauterine growth retardation (IUGR) is a serious reproductive problem in humans. The objective of this study was to investigate the effects of daily maternal curcumin supplementation during pregnancy on placental function and fetal growth in a mouse model of IUGR fed the low-protein (LP) diet. Pregnant mice were divided into four groups: (1) normal protein (19% protein) diet (NP); (2) LP (8% protein) diet; (3) LP diet + 100 mg/kg curcumin (LPL); (4) LP diet +400 mg/kg curcumin (LPH). The results showed that the LP group decreased fetal weight, placental weight, placental efficiency, serum progesterone level, placental glutathione peroxidase activity activity, blood sinusoids area, and antioxidant gene expression of placenta. In addition, in comparison with the NP group, LP diet increased serum corticosterone level, placental malondialdehyde content, and apoptotic index. Daily curcumin administration decreased the placental apoptosis, while it increased placental efficiency, placental redox balance, blood sinusoids area, and antioxidant-related protein expression in fetal liver. The antioxidant gene expression of placenta and fetal liver was normalized to the NP level after curcumin administration. In conclusion, daily curcumin supplementation could improve maternal placental function and fetal growth in mice with IUGR.

scholarly journals Sexual Dimorphism in Offspring Glucose-Sensitive Hypothalamic Gene Expression and Physiological Responses to Maternal High-Fat Diet Feeding

Endocrinology ◽  
2014 ◽  
Vol 155 (6) ◽  
pp. 2144-2154 ◽  
Author(s):  
Laura Dearden ◽  
Nina Balthasar
Keyword(s):  
Gene Expression ◽  
Sexual Dimorphism ◽  
Glucose Homeostasis ◽  
Maternal Diet ◽  
Female Offspring ◽  
In Utero ◽  
High Fat ◽  
Metabolic Balance ◽  
High Sugar ◽  
Female Specific

A wealth of animal and human studies demonstrate that early life environment significantly influences adult metabolic balance, however the etiology for offspring metabolic misprogramming remains incompletely understood. Here, we determine the effect of maternal diet per se on offspring sex-specific outcomes in metabolic health and hypothalamic transcriptome regulation in mice. Furthermore, to define developmental periods of maternal diet misprogramming aspects of offspring metabolic balance, we investigated offspring physiological and transcriptomic consequences of maternal high-fat/high-sugar diet feeding during pregnancy and/or lactation. We demonstrate that female offspring of high-fat/high-sugar diet-fed dams are particularly vulnerable to metabolic perturbation with body weight increases due to postnatal processes, whereas in utero effects of the diet ultimately lead to glucose homeostasis dysregulation. Furthermore, glucose- and maternal-diet sensitive gene expression modulation in the paraventricular hypothalamus is strikingly sexually dimorphic. In summary, we uncover female-specific, maternal diet-mediated in utero misprogramming of offspring glucose homeostasis and a striking sexual dimorphism in glucose- and maternal diet-sensitive paraventricular hypothalamus gene expression adjustment. Notably, female offspring metabolic vulnerability to maternal high-fat/high-sugar diet propagates a vicious cycle of obesity and type 2 diabetes in subsequent generations.

scholarly journals Maternal high-fat diet during pregnancy with concurrent phthalate exposure leads to abnormal placentation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Athilakshmi Kannan ◽  
Juanmahel Davila ◽  
Liying Gao ◽  
Saniya Rattan ◽  
Jodi A. Flaws ◽  
...  
Keyword(s):  
Maternal Diet ◽  
Critical Factor ◽  
High Fat ◽  
Placental Development ◽  
Daily Diet ◽  
Exposure Pathway ◽  
Fatty Food ◽  
Pregnant Mice ◽  
The Impact ◽  
Dehp Exposure

AbstractDi(2-ethylhexyl) phthalate (DEHP) is a synthetic chemical commonly used for its plasticizing capabilities. Because of the extensive production and use of DEHP, humans are exposed to this chemical daily. Diet is a significant exposure pathway and fatty food contain the highest level of phthalates. The impact on pregnancy following DEHP exposure and the associated interaction of high fat (HF) diet remains unknown. Here we report that exposure of pregnant mice to an environmentally relevant level of DEHP did not affect pregnancy. In contrast, mice fed a HF diet during gestation and exposed to the same level of DEHP display marked impairment in placental development, resulting in poor pregnancy outcomes. Our study further reveals that DEHP exposure combined with a HF diet interfere with the signaling pathway controlled by nuclear receptor PPARγ to adversely affect differentiation of trophoblast cells, leading to compromised vascularization and glucose transport in the placenta. Collectively, these findings demonstrate that maternal diet during pregnancy is a critical factor that determines whether exposure to an environmental toxicant results in impaired placental and fetal development, causing intrauterine growth restriction, fetal morbidity, and mortality.

Sign in / Sign up

Export Citation Format

Share Document