Paternally induced transgenerational inheritance of susceptibility to diabetes in mammals

Wei, Yanchang; Yang, Cai‐Rong; Wei, Yanping; Zhao, Zhen-Ao; Hou, Yi; Schatten, Heide; Sun, Qing‐Yuan

doi:10.1073/pnas.1321195111

Cited by 393 publications

(367 citation statements)

References 35 publications

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“…Induction of a pre-diabetic state in fathers (feeding a high fat diet in combination with streptozotocin injection) altered pancreatic gene expression pattern in male offspring. 26 In our study, we detected altered gene expression in the liver of HFD male offspring compared to LFD male offspring. Several of the differentially expressed genes play a role in lipid metabolism (Acaca, Fasn, Por, and Sqle) and are involved in the oxidative-reduction pathway (Mt1, Mt2, Por, and Sqle).…”

Section: Discussionmentioning

confidence: 57%

“…24,25 A number of studies have reported that a parental diet containing high fat or imposing calorie restriction modulates the phenotype of the offspring. [26][27][28] Under-nourishment in utero leads to methylome changes in the sperm of the male progeny and metabolic changes that are inherited to the subsequent generation. 29 A high fat paternal diet in rodents changes the insulin and glucose levels in offspring serum and induces an abnormal response after glucose or insulin injections.…”

Section: Introductionmentioning

confidence: 99%

“…29 A high fat paternal diet in rodents changes the insulin and glucose levels in offspring serum and induces an abnormal response after glucose or insulin injections. 26 The change in glucose tolerance in rodents is associated with deregulation of pancreatic islet gene expression, including upregulation of IL13 receptor a2 (IL13Ra2) mRNA level and reduced CpG methylation at the IL13Ra2 promoter regions. 30 In addition, offspring fertility decreased after exposure of the father to a high fat diet.…”

Section: Introductionmentioning

confidence: 99%

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Effect of high fat diet on paternal sperm histone distribution and male offspring liver gene expression

et al. 2015

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Several studies have described phenotypic changes in the offspring of mice exposed to a variety of environmental factors, including diet, toxins, and stress; however, the molecular pathways involved in these changes remain unclear. Using a high fat diet (HFD)-induced obesity mouse model, we examined liver gene expression in male offspring and analyzed chromatin of paternal spermatozoa. We found that the hepatic mRNA level of 7 genes (out of 20 evaluated) was significantly altered in HFD male offspring compared to control mice, suggesting that phenotypic changes in the offspring depend on parental diet. We examined 7 imprinted loci in spermatozoa DNA from HFD-treated and control fathers by bisulfite sequencing, but did not detect changes in DNA methylation associated with HFD. Using chromatin immunoprecipitation followed by high-throughput sequencing, we found differential histone H3-occupancy at genes involved in the regulation of embryogenesis and differential H3K4me1-enrichment at transcription regulatory genes in HFD fathers vs. control mice. These results suggest that dietary exposure can modulate histone composition at regulatory genes implicated in developmental processes.

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Section: Discussionmentioning

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of high fat diet on paternal sperm histone distribution and male offspring liver gene expression

et al. 2015

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“…It follows that much of our knowledge of transgenerational epigenetic inheritance in mammals pertains largely to inbred mice, where maternally or paternally induced transmission can come in the form of covalent modifications to DNA and histone methylation (e.g. Padmanabhan et al 2013;Wei et al 2014;Siklenka et al 2015) and altered RNA expression (Wagner et al 2008), often in a breeding scheme-dependent manner (Yuan et al 2015). Not surprisingly, evidence for similar effects occurring in long-lived and out-bred farm animals is scarce, leading González-Recio et al (2015) to question its importance in livestock production.…”

Section: Inter(trans)generational Inheritancementioning

confidence: 99%

Epigenetics and developmental programming of welfare and production traits in farm animals

Sinclair

Rutherford

Wallace

et al. 2016

Reprod. Fertil. Dev.

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Abstract. The concept that postnatal health and development can be influenced by events that occur in utero originated from epidemiological studies in humans supported by numerous mechanistic (including epigenetic) studies in a variety of model species. Referred to as the 'developmental origins of health and disease' or 'DOHaD' hypothesis, the primary focus of large-animal studies until quite recently had been biomedical. Attention has since turned towards traits of commercial importance in farm animals. Herein we review the evidence that prenatal risk factors, including suboptimal parental nutrition, gestational stress, exposure to environmental chemicals and advanced breeding technologies, can determine traits such as postnatal growth, feed efficiency, milk yield, carcass composition, animal welfare and reproductive potential. We consider the role of epigenetic and cytoplasmic mechanisms of inheritance, and discuss implications for livestock production and future research endeavours. We conclude that although the concept is proven for several traits, issues relating to effect size, and hence commercial importance, remain. Studies have also invariably been conducted under controlled experimental conditions, frequently assessing single risk factors, thereby limiting their translational value for livestock production. We propose concerted international research efforts that consider multiple, concurrent stressors to better represent effects of contemporary animal production systems.

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“…Epigenetic inheritance has been demonstrated in several species including worm (2), fly (3) and mouse species (4,5). Epigenetic inheritance can be modulated by environmental factors and transmitted to subsequent generations via germline cells (6,7). …”

Section: Introductionmentioning

confidence: 99%

Exposure to the widely used herbicide atrazine results in deregulation of global tissue-specific RNA transcription in the third generation and is associated with a global decrease of histone trimethylation in mice

et al. 2016

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The epigenetic events imposed during germline reprogramming and affected by harmful exposure can be inherited and transferred to subsequent generations via gametes inheritance. In this study, we examine the transgenerational effects promoted by widely used herbicide atrazine (ATZ). We exposed pregnant outbred CD1 female mice and the male progeny was crossed for three generations with untreated females. We demonstrate here that exposure to ATZ affects meiosis, spermiogenesis and reduces the spermatozoa number in the third generation (F3) male mice. We suggest that changes in testis cell types originate from modified transcriptional network in undifferentiated spermatogonia. Importantly, exposure to ATZ dramatically increases the number of transcripts with novel transcription initiation sites, spliced variants and alternative polyadenylation sites. We found the global decrease in H3K4me3 occupancy in the third generation males. The regions with altered H3K4me3 occupancy in F3 ATZ-derived males correspond to altered H3K4me3 occupancy of F1 generation and 74% of changed peaks in F3 generation are associated with enhancers. The regions with altered H3K4me3 occupancy are enriched in SP family and WT1 transcription factor binding sites. Our data suggest that the embryonic exposure to ATZ affects the development and the changes induced by ATZ are transferred up to three generations.

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Paternally induced transgenerational inheritance of susceptibility to diabetes in mammals

Cited by 393 publications

References 35 publications

Effect of high fat diet on paternal sperm histone distribution and male offspring liver gene expression

Effect of high fat diet on paternal sperm histone distribution and male offspring liver gene expression

Epigenetics and developmental programming of welfare and production traits in farm animals

Exposure to the widely used herbicide atrazine results in deregulation of global tissue-specific RNA transcription in the third generation and is associated with a global decrease of histone trimethylation in mice

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