From maternal metabolome to placental development: thiamine-driven placental Notch-PI3K/AKT pathway coordinates placental angiogenesis and nutrient transport
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ABSTRACT:
INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase
PROVIDER: MTBLS12796 | MetaboLights | 2025-07-30
REPOSITORIES: MetaboLights
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Project description:RNA sequencing was performed to quantify differential gene expression between pig placentae exposed to thermoneutral control or cyclic heat stress conditions between d40 and d60 of gestation (early-mid gestation). Placental samples from female fetuses were collected at d60 of gestation and were subjected to sequencing library preparation and NovaSeq6000 sequencing. 150 bp paired-end reads were generated from each sample. A total of 169 genes were differentially expressed between control and heat stress placentae, of which 35 genes were upregulated and 134 genes were downregulated by maternal heat stress. Gene ontology and pathway enrichment analysis revealed the differentially expressed genes are associated with placental nutrient transporter and metabolism.
2021-04-15 | GSE168571 | GEO
Project description:Maternal nutrition during embryonic development and lactation influences multiple aspects of offspring health. Using mice, this study investigates the effects of maternal caloric restriction (CR) during mid-gestation and lactation on offspring neonatal development and on adult metabolic function when challenged by a high fat diet (HFD). The CR maternal model produced male and female offspring that were significantly smaller, in terms of weight and length, and females had delayed puberty. Adult offspring born to CR dams had a sexually dimorphic response to the high fat diet. Compared to offspring of maternal control dams, adult female, but not male, CR offspring gained more weight in response to high fat diet at 10 weeks. In adipose tissue of male HFD offspring, maternal undernutrition resulted in blunted expression of genes associated with weight gain and increased expression of genes that protect against weight gain. Regardless of maternal nutrition status, HFD male offspring showed increased expression of genes associated with nonalcoholic liver disease (NAFLD). Furthermore, we observed significant, sexually dimorphic differences in serum TSH. These data reveal tissue- and sex-specific changes in gene and hormone regulation following mild maternal undernutrition, which may offer protection against diet induced weight gain in adult male offspring.
2024-01-04 | GSE247985 | GEO
Project description:Maternal diet is associated with the development of metabolism-related and other non-communicable diseases in offspring. Underlying mechanisms, functional profiles, and molecular markers are only starting to be revealed. Here, we explored the physiological and molecular impact of maternal Western-style diet on the liver of male and female offspring. C57BL/6 dams were exposed to either a low fat/low cholesterol diet (LFD) or a Western-style high fat/high cholesterol diet (WSD) for six weeks before mating, as well as during gestation and lactation. Dams and offspring were sacrificed at postnatal day 14, and body, liver, and blood parameters were assessed. The impact of maternal WSD on the pups' liver gene expression was characterised by whole-transcriptome microarray analysis. Exclusively male offspring had significantly higher body weight upon maternal WSD. In offspring of both sexes of WSD dams, liver and blood parameters, as well as hepatic gene expression profiles were changed. In total, 686 and 604 genes were differentially expressed in liver (pM-bM-^IM-$0.01) of males and females, respectively. Only 10% of these significantly changed genes overlapped in both sexes. In males, in particular alterations of gene expression with respect to developmental functions and processes were observed, such as Wnt/beta-catenin signalling. In females, mainly genes important for lipid metabolism, including cholesterol synthesis, were changed. We conclude that maternal WSD affects physiological parameters and induces substantial changes in the molecular profile of the liver in two-week-old pups. Remarkably, the observed biological responses of the offspring reveal pronounced sex-specificity. C57BL/6 dams were exposed to either a low fat/low cholesterol diet (LFD) or a Western-style high fat/high cholesterol diet (WSD) as six weeks pre-treatment before mating, as well as during gestation and lactation. Offspring were sacrificed at postnatal week two, livers were removed and RNA samples were subjected to gene expression profiling.
2013-11-27 | E-GEOD-46359 | biostudies-arrayexpress
Project description:one-carbon metabolism in the liver plays a critical role in placental and fetal growth. Impaired functioning of one-carbon metabolism is associated with increased homocysteine (Hcy) levels. In this study, we applied a comprehensive proteomic approach to identify differential expression of proteins related to one-carbon metabolism in the livers of rat offspring as an effect of maternal food restriction during gestation. We determined that betaine-homocysteine S-methyltransferase 1 (BHMT1), methylenetetrahydrofolate dehydrogenase 1 (MTHFD1), and ATP synthase subunit beta mitochondrial (ATP5B) expression levels were significantly reduced in the livers of rat offspring exposed to maternal food restriction during gestation compared with in the offspring of rats fed a normal diet (p<0.05).
2015-09-07 | PXD002578 | Pride
Project description:<p>Placental dysplasia critically impairs fetal growth and development by disrupting nutrient supply. Thiamine, predominantly in its bioactive form thiamine pyrophosphate, serves as an essential coenzyme in mitochondrial energy metabolism, yet its regulatory role in placental development remains elusive.</p><p>Objectives</p><p>This study systematically unraveled the metabolic network disparities between sows with different reproductive potentials and elucidates the mechanisms by which characterized metabolites enhance placental angiogenesis and nutrient transport efficiency to promote fetal development.</p><p>Methods</p><p>We initially analyzed plasma and fecal metabolite composition and fecal microbial composition of sows with high and low reproductive potential by 16S rRNA sequencing and untargeted metabolomics. Subsequently, we evaluated the effects of thiamine, the identified characterized metabolite, on the angiogenesis and nutrient transport functions of placenta and the growth and development of offspring in a rat model, as well as verified the effects of thiamine on the cell migration of placental trophoblast cells by in vitro experiment.</p><p>Results</p><p>Sows with high reproductive potential exhibit a distinct metabolic profile with significantly elevated plasma arginine and fecal thiamine levels and the abundance of gut thiamine-synthesizing bacteria increases in parallel. Maternal thiamine supplementation effectively promotes offspring growth and enhances thiamine metabolism in the maternal-placental-fetal axis. Meanwhile, thiamine improves placental function by increasing thiamine-related metabolic enzymes and acetyl-CoA content in the placenta. Furthermore, thiamine facilitates placental angiogenesis via activation of the Notch signaling pathway and initiates the Notch-PI3K/AKT cascade reaction, which regulates placental nutrient metabolism efficiency and transporter expression.</p><p>Conclusions</p><p>Maternal supplementation with thiamine during gestation and lactation promotes placental development and enhances offspring growth through activation of the Notch signaling pathway.</p>
2025-07-29 | MTBLS12795 | MetaboLights
Project description:The mammalian placenta is both the physical interface between mother and fetus, and the source of endocrine signals that target the maternal hypothalamus, priming females for parturition, lactation and motherhood. Despite the importance of this connection, the effects of altered placental signaling on the maternal brain are understudied. Here, we show that placental dysfunction alters gene expression in the maternal brain, with the potential to affect maternal behavior. Using a cross between the house mouse and the Algerian mouse in which hybrid placental development is abnormal, we sequenced late gestation placental and maternal medial preoptic area transcriptomes and quantified differential expression and placenta-maternal brain co-expression between normal and hybrid pregnancies. The expression of Fmn1, Drd3, Caln1 and Ctsr was significantly altered in the brains of females exposed to hybrid placentas. Most strikingly, expression patterns of placenta-specific gene families and Drd3 in the brains of house mouse females carrying hybrid litters matched those of female Algerian mice, the paternal species in the cross. Our results indicate that the paternally-derived placental genome can influence the expression of maternal-fetal communication genes, including placental hormones, suggesting an effect of the offspring's father on the mother’s brain.
2019-12-31 | GSE126469 | GEO
Project description:Background & Aims: The influences of the maternal diet during gestation has been suggested to be involved in the development of different aspects of the metabolic syndrome. In our mouse model we characterised the role of maternal western diet in the development of non-alcoholic fatty liver disease (NAFLD) in the offspring. Methods: Female mice were fed either a western (W) or low-fat control (L) semi-synthetic diet before and during gestation and lactation. At weaning, male offspring were assigned either the W or the L diet, generating four experimental groups: WW, WL, LW and LL offspring. Biochemical, histological and epigenetic indicators were investigated at 29 weeks of age. Results: Male offspring exposed to prenatal western style diet and to a post-weaning W diet (WW) showed hepatomegaly combined with increased hepatic cholesterol and triglycerides accumulation, compared to LW offspring. This was associated with up-regulation of de novo lipid synthesis and dysregulation of beta oxidation and lipid storage. Elevated hepatic transaminases and increased expression of Tnfa, Cd11, Mcp1 and Tgfb underpin the severity of liver injury. Histological analysis supported the presence of steatohepatitis in the WW offspring. In addition alterations in DNA methylation in key metabolic genes (Ppara, Insig, Fasn) were detected. Conclusion: Maternal dietary fat intake during critical developmental phases programs susceptibility to liver disease in mouse offspring. This was mediated by shifts in lipid metabolism and inflammatory response. Long lasting epigenetic changes may underlie this dysregulation 4 groups of 6 male mouse were analysed , 1 experimental and 1 biological outlier was excluded , so n=6,5,5,6 in the 4 groups (LL,LW,WL,WW)
2014-01-21 | E-GEOD-44901 | biostudies-arrayexpress
Project description:Developmental programming is the concept that environmental factors, particularly during foetal life, can alter development, metabolism and physiology of an organism and this can have consequences later in life. There is growing interest in developmental programming in livestock species, particularly effects of maternal pregnancy nutrition, which is easy to manipulate. Recent research, using a sheep model, has shown that milk production in ewe offspring may be susceptible to maternal nutritional programming, such that over nutrition (ad libitum) of the pregnant dam, compared with maintenance nutrition, may impair their first lactation performance and result in the weaning of lighter lambs. RNA-seq was performed to identify gene expression differences as a result of maternal nutrition in ewe offspring during their first parity. Samples were collected in late pregnancy and during lactation, allowing us to examine gene expression changes during maturation of the ovine mammary gland. Three biological replicates were sequenced for each of the treatment conditions (maternal nutrition: sub-maintenance, maintenance, and ad libitum) and time points (late pregnancy and lactation). Each biological replicate consisted of RNA from multiple individuals (late pregnancy n=3, lactation n=2).
2015-07-29 | E-GEOD-71424 | biostudies-arrayexpress
Project description:Modern lifestyle is associated with a major consumption of ultra-processed foods (UPF) due to their practicality and palatability. The ingestion of emulsifiers, a main additive in UPFs, has been related to gut inflammation, microbiota dysbiosis, adiposity and obesity. Maternal unbalanced nutritional habits during embryonic and perinatal stages perturb offspring’s long-term metabolic health, thus increasing obesity and associated comorbidity risk. However, whether maternal emulsifier consumption influences developmental programming in the offspring remains unknown. Here we show that, in mice, maternal consumption of dietary emulsifiers (1% CMC and 1% P80 in drinking water), during gestation and lactation, perturbs the development of hypothalamic energy balance regulation centers of the progeny, leads to metabolic impairments, cognition deficits and induces anxiety-like traits in a sex-specific manner. Our findings support the notion that maternal consumption of emulsifiers, common additives of UPFs, causes mild metabolic and neuropsychological malprogramming in the progeny. Our data call for nutritional advice during gestation.
2023-07-31 | GSE231769 | GEO
Project description:Background & Aims: The influences of the maternal diet during gestation has been suggested to be involved in the development of different aspects of the metabolic syndrome. In our mouse model we characterised the role of maternal western diet in the development of non-alcoholic fatty liver disease (NAFLD) in the offspring. Methods: Female mice were fed either a western (W) or low-fat control (L) semi-synthetic diet before and during gestation and lactation. At weaning, male offspring were assigned either the W or the L diet, generating four experimental groups: WW, WL, LW and LL offspring. Biochemical, histological and epigenetic indicators were investigated at 29 weeks of age. Results: Male offspring exposed to prenatal western style diet and to a post-weaning W diet (WW) showed hepatomegaly combined with increased hepatic cholesterol and triglycerides accumulation, compared to LW offspring. This was associated with up-regulation of de novo lipid synthesis and dysregulation of beta oxidation and lipid storage. Elevated hepatic transaminases and increased expression of Tnfa, Cd11, Mcp1 and Tgfb underpin the severity of liver injury. Histological analysis supported the presence of steatohepatitis in the WW offspring. In addition alterations in DNA methylation in key metabolic genes (Ppara, Insig, Fasn) were detected. Conclusion: Maternal dietary fat intake during critical developmental phases programs susceptibility to liver disease in mouse offspring. This was mediated by shifts in lipid metabolism and inflammatory response. Long lasting epigenetic changes may underlie this dysregulation
2014-01-21 | GSE44901 | GEO