Paternal malnutrition programs offspring’s breast cancer risk and tumor metabolism in a mouse model (small RNA-seq)
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ABSTRACT:
PROVIDER: PRJNA471323 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
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| SRR7162890_1.fastq.gz | Fastqsanger.gz | |||
| SRR7162890_2.fastq.gz | Fastqsanger.gz | |||
| SRR7162900_1.fastq.gz | Fastqsanger.gz | |||
| SRR7162900_2.fastq.gz | Fastqsanger.gz | |||
| SRR7162891_1.fastq.gz | Fastqsanger.gz |
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Project description:Paternal malnutrition programs offspring’s breast cancer risk and tumor metabolism in a mouse model
| PRJNA471320 | ENA
Project description:Paternal malnutrition programs offspring’s breast cancer risk and tumor metabolism in a mouse model (MBD-seq)
| PRJNA471326 | ENA
Project description:BACKGROUND:While many studies have shown that maternal factors in pregnancy affect the cancer risk for offspring, few studies have investigated the impact of paternal exposures on their progeny's risk of this disease. Population studies generally show a U-shaped association between birthweight and breast cancer risk, with both high and low birthweight increasing the risk compared with average birthweight. Here, we investigated whether paternal malnutrition would modulate the birthweight and later breast cancer risk of daughters. METHODS:Male mice were fed AIN93G-based diets containing either 17.7% (control) or 8.9% (low-protein (LP)) energy from protein from 3 to 10 weeks of age. Males on either group were mated to females raised on a control diet. Female offspring from control and LP fathers were treated with 7,12-dimethylbenz[a]anthracene (DMBA) to initiate mammary carcinogenesis. Mature sperm from fathers and mammary tissue and tumors from female offspring were used for epigenetic and other molecular analyses. RESULTS:We found that paternal malnutrition reduces the birthweight of daughters and leads to epigenetic and metabolic reprogramming of their mammary tissue and tumors. Daughters of LP fathers have higher rates of mammary cancer, with tumors arising earlier and growing faster than in controls. The energy sensor, the AMP-activated protein kinase (AMPK) pathway, is suppressed in both mammary glands and tumors of LP daughters, with consequent activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, LP mammary tumors show altered amino-acid metabolism with increased glutamine utilization. These changes are linked to alterations in noncoding RNAs regulating those pathways in mammary glands and tumors. Importantly, we detect alterations in some of the same microRNAs/target genes found in our animal model in breast tumors of women from populations where low birthweight is prevalent. CONCLUSIONS:Our study suggests that ancestral paternal malnutrition plays a role in programming offspring cancer risk and phenotype by likely providing a metabolic advantage to cancer cells.
| S-EPMC6117960 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-06-14 | GSE114423 | GEO
Project description:We found that LP daughters have lower birthweight, alterations in mammary gland morphology and higher rates of mammary cancer. Further, we found that mammary glands and tumors of LP daughters are metabolic rewired, with alterations in the AMPK and amino-acid metabolism pathways. These changes were associated with differential expression of miRNAs 451a, miR-200c and miR-92a. Importantly, some of the same miRNAs and target genes alterations were detected in breast tumors of women from populations with high rates of low birthweight.
2018-06-14 | GSE114422 | GEO
Project description:We found that LP daughters have lower birthweight, alterations in mammary gland morphology and higher rates of mammary cancer. Further, we found that mammary glands and tumors of LP daughters are metabolic rewired, with alterations in the AMPK and amino-acid metabolism pathways. These changes were associated with differential expression of miRNAs 451a, miR-200c and miR-92a. Importantly, some of the same miRNAs and target genes alterations were detected in breast tumors of women from populations with high rates of low birthweight.
2018-06-14 | GSE114421 | GEO
Project description:<p>The gut microbiota operates at the interface of host-environment interactions to influence human homeostasis and metabolic networks. Environmental factors that unbalance gut microbial ecosystems can therefore elicit physiological and disease-associated responses across somatic tissues. However, the systemic impact of the gut microbiome on the germline - and consequently on the F1 offspring it gives rise to - is unexplored. Here we show that the gut microbiota act as a key interface between paternal preconception environment and intergenerational health in mice. Perturbations to the gut microbiota of prospective fathers increase the probability of their offspring presenting with low birth weight, severe growth restriction and premature mortality. Transmission of disease risk occurs via the germline and is provoked by pervasive gut microbiome perturbations, including non-absorbable antibiotics or osmotic laxatives, but is rescued by restoring the paternal microbiota before conception. This effect is linked with a dynamic response to induced dysbiosis in the male reproductive system, including impaired leptin signalling, altered testicular metabolite profiles and remapped small RNA payloads in sperm. As a result, dysbiotic fathers trigger an elevated risk of in utero placental insufficiency, revealing a placental origin of mammalian intergenerational effects. Our study defines a regulatory ‘gut-germline axis’ in males, which is sensitive to environmental exposures and programs offspring fitness through impacting placental function.</p>
2024-02-12 | MTBLS1629 | MetaboLights
Project description:Protein malnutrition promotes hepatic steatosis, decreases insulin-like growth factor (IGF)-I production, and retards growth. In order to identify new molecules involved in such changes, we conducted DNA microarray analysis for liver samples of rats fed isoenergetic low protein diet for 8 hours, and identified fibroblast growth factor 21 (Fgf21) as one of the most strongly up-regulated genes under conditions of acute protein malnutrition (P<0.05, FDR<0.001). In addition, amino acid deprivation from the culture media increased Fgf21 mRNA levels in rat liver-derived RL-34 cells (P<0.01). Thus, it was suggested that amino acid limitation directly increases Fgf21 expression. FGF21 is a polypeptide hormone that regulates glucose and lipid metabolism. Using transgenic mice, FGF21 has also been shown to promote a growth hormone-resistant state and suppress IGF-I. Therefore, to further determine whether the up-regulation of Fgf21 under protein malnutrition causes hepatic steatosis and growth retardation following decrease in IGF-I, we fed isoenergetic low protein diet to Fgf21-knockout (KO) mice. Fgf21-KO did not rescue growth retardation and reduced plasma IGF-I concentration of mice fed the low-protein diet. Meanwhile, Fgf21-KO mice showed greater epididymal white adipose tissue weight as well as hepatic triglyceride and cholesterol levels under protein malnutrition (P<0.05). Taken together, we showed that protein deprivation directly increases Fgf21 expression. However, growth retardation and decreased IGF-I were not mediated by increased FGF21 expression under protein malnutrition. Furthermore, up-regulated FGF21 rather appears to have a protective effect against obesity and hepatic steatosis in protein malnourished animals. Livers of rats from 2 groups (control (15P) or low-protain (5P) diet fed groups), total of 6 samples (3 replicates for each group) were analyzed.
2015-01-15 | E-GEOD-64970 | biostudies-arrayexpress
Project description:Microbes Malnutrition Microglia
| PRJNA575001 | ENA
Project description:The importance of fathers' engagement in care and its critical role in the offspring’s cognitive and emotional development is now well established. Yet, little is known on the underlying neurobiology due to the lack of appropriate animal models. In the socially monogamous and bi-parental prairie vole (Microtus ochrogaster), while most virgin males show spontaneous paternal behaviors (Paternal), others display pup-directed aggression (Attackers). Here we took advantage of this phenotypic dichotomy and used RNA-sequencing in three important brain areas to characterize gene expression associated with paternal behaviors of Paternal males and compare it to experienced fathers and mothers. This strategy allowed the identification of spontaneous paternal behaviors independently from fatherhood and pair-bonding. While Paternal males displayed the same range and extent of paternal behaviors than experienced Fathers, the nucleus accumbens (NAc) and medial preoptic area (MPOA) transcriptomes mainly reflected pair-bonded status or sex differences, respectively. The lateral septum (LS) transcriptome, however, primarily reflected phenotypic differences between Paternal and Attackers and suggested the involvement of the mitochondria, RNA translation, and protein degradation processes. Altogether, these observations highlight a marked structure- and phenotype-specific pattern of gene expression underlying paternal behaviors in prairie voles and highlight similarities and differences from those underlying fatherhood.
2022-10-05 | GSE190213 | GEO