Male-lineage transmission of an acquired metabolic phenotype induced by grand-paternal obesity

Cropley, Jennifer E.; Eaton, Sally A.; Aiken, Alastair; Young, Paul E.; Giannoulatou, Eleni; Ho, Joshua W. K.; Buckland, Michael E.; Keam, Simon P.; Hutvágner, György; Humphreys, David T.; Langley, Katherine G.; Henstridge, Darren C.; Martin, David I. K.; Febbraio, Mark A.; Suter, Catherine M.

doi:10.1016/j.molmet.2016.06.008

Cited by 142 publications

(132 citation statements)

References 57 publications

(83 reference statements)

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“…miRNAs and tRNAs, such as miR-10 and tRF-5-GluCTC, which are altered in sperm of grandoffspring of obese Avy/a males, could be interacting with the Ago2 enzyme in the oocyte cytoplasm to alter embryonic development (Cropley et al, 2016). Thus, small RNAs are likely to be important for epigenetically-mediated intergenerational and transgenerational phenotypes in multiple mammalian models.…”

Section: Impact Of Sperm Phenotypes On Offspring Metabolismmentioning

confidence: 99%

Epigenetic Mechanisms of Transmission of Metabolic Disease across Generations

2017

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Both human and animal studies indicate that environmental exposures experienced during early life can robustly influence risk for adult disease. Moreover, environmental exposures experienced by parents during either intrauterine or postnatal life can also influence the health of their offspring, thus initiating a cycle of disease risk across generations. In this perspective, we focus on epigenetic mechanisms in germ cells, including DNA methylation, histone modification, and non-coding RNAs, which collectively may provide a non-genetic molecular legacy of prior environmental exposures and influence transcriptional regulation, developmental trajectories, and adult disease risk in offspring.

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Section: Impact Of Sperm Phenotypes On Offspring Metabolismmentioning

confidence: 99%

Epigenetic Mechanisms of Transmission of Metabolic Disease across Generations

2017

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“…; Cropley et al . ). Furthermore, paternal obesity results in overactivation of the RAS in offspring adipose tissue, associated with poor glucose metabolism and increased inflammatory status (Ornellas et al .…”

Section: Introductionmentioning

confidence: 97%

Paternal diet impairs F1 and F2 offspring vascular function through sperm and seminal plasma specific mechanisms in mice

Morgan

Paganopoulou

Akhtar

et al. 2019

The Journal of Physiology

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Key points A low protein diet had minimal effects on paternal cardiovascular function or renin–angiotensin system activity. Paternal low protein diet modified F1 neonatal and adult offspring renin–angiotensin system activity and cardiovascular function in a sperm and/or seminal plasma specific manner. Paternal low protein diet modified F1 male offspring testicular expression of central epigenetic regulators. Significant changes in F2 neonatal offspring growth and tissue angiotensin‐converting enzyme activity were programmed by paternal low protein diet in a sperm and/or seminal plasma specific manner. Abstract Although the impact of maternal diet on adult offspring health is well characterized, the role that a father's diet has on his offspring's health remains poorly defined. We establish the significance of a sup‐optimal paternal low protein diet for offspring vascular homeostasis and define the sperm and seminal plasma specific programming effects on cardiovascular health. Male C57BL6 mice were fed either a control normal protein diet (NPD; 18% protein) or an isocaloric low protein diet (LPD; 9% protein) for a minimum of 7 weeks. Using artificial insemination, in combination with vasectomized male mating, we generated offspring derived from either NPD or LPD sperm (devoid of seminal plasma) but in the presence of NPD or LPD seminal plasma (devoid of sperm). We observed that either LPD sperm or seminal fluid at conception impaired adult offspring vascular function in response to both vasoconstrictors and dilators. Underlying these changes in vascular function were significant changes in serum, lung and kidney angiotensin‐converting enzyme (ACE) activity, established in F1 offspring from 3 weeks of age, maintained into adulthood and present also within juvenile F2 offspring. Furthermore, we observed differential expression of multiple central renin–angiotensin system regulators in adult offspring kidneys. Finally, paternal diet modified the expression profiles of central epigenetic regulators of DNA methylation, histone modifications and RNA methylation in adult F1 male testes. These novel data reveal the impact of sub‐optimal paternal nutrition on offspring cardiovascular well‐being, programming offspring cardiovascular function through both sperm and seminal plasma specific mechanisms over successive generations.

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“…Sperm miRNAs from traumatized male mice injected into wild‐type oocytes reproduced trauma‐associated behavioural and metabolic changes in resulting offspring (Gapp et al., ; Rodgers et al., , ). In similar injection‐based experiments, intergenerational development of metabolic disorders in response to high‐fat diet (HFD) was mediated by sperm tRNA‐derived small RNAs (tsRNA) (Chen et al., ; Cropley et al., ; Sharma et al., ). Sperm miRNA profiles also change in response to HFD, and offspring have an obesity‐like phenotype with effects into the G 2 generation (Fullston, Ohlsson‐teague, Print, Sandeman, & Lane, ; Fullston et al., ).…”

Section: Introductionmentioning

confidence: 99%

Daphnia magna microRNAs respond to nutritional stress and ageing but are not transgenerational

et al. 2018

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Maternal effects, where the performance of offspring is determined by the condition of their mother, are widespread and may in some cases be adaptive. The crustacean Daphnia magna shows strong maternal effects: offspring size at birth and other proxies for fitness are altered when their mothers are older or when mothers have experienced dietary restriction. The mechanisms for this transgenerational transmission of maternal experience are unknown, but could include changes in epigenetic patterning. MicroRNAs (miRNAs) are regulators of gene expression that have been shown to play roles in intergenerational information transfer, and here, we test whether miRNAs are involved in D. magna maternal effects. We found that miRNAs were differentially expressed in mothers of different ages or nutritional state. We then examined miRNA expression in their eggs, their adult daughters and great granddaughters, which did not experience any treatments. The maternal (treatment) generation exhibited differential expression of miRNAs, as did their eggs, but this was reduced in adult daughters and lost by great granddaughters. Thus, miRNAs are a component of maternal provisioning, but do not appear to be the cause of transgenerational responses under these experimental conditions. MicroRNAs may act in tandem with egg provisioning (e.g., with carbohydrates or fats), and possibly other small RNAs or epigenetic modifications.

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Male-lineage transmission of an acquired metabolic phenotype induced by grand-paternal obesity

Cited by 142 publications

References 57 publications

Epigenetic Mechanisms of Transmission of Metabolic Disease across Generations

Epigenetic Mechanisms of Transmission of Metabolic Disease across Generations

Paternal diet impairs F1 and F2 offspring vascular function through sperm and seminal plasma specific mechanisms in mice

Daphnia magna microRNAs respond to nutritional stress and ageing but are not transgenerational

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