Folate treatment of pregnant rat dams abolishes metabolic effects in female offspring induced by a paternal pre-conception unhealthy diet

Li, Jian; Lu, Yongping; Tsuprykov, Oleg; Hasan, Ahmed A.; Reichetzeder, Christoph; Tian, Miao; Zhang, Xiao Li; Zhang, Qin; Sun, Guoying; Guo, Jingli; Gaballa, Mohamed M S; Peng, Xiaoning; Lin, Ge; Hocher, Berthold

doi:10.1007/s00125-018-4635-x

Cited by 22 publications

(13 citation statements)

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“…So far most of the animal studies dealing with paternal programming used paternal high-fat diet models prior to mating to investigate potential underlying mechanisms. We exposed male rats to a high-salt-fat-sugar diet mimicking an unhealthy fast food diet often eaten by young men as recently described [30]. Our study was designed to examine the effect of feeding male rats HFSSD over two generations (F0 and F1) on their offspring’s (F2) liver function, lipid profile and gut microbiome composition.…”

Section: Discussionmentioning

confidence: 99%

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Paternal Programming of Liver Function and Lipid Profile Induced by a Paternal Pre-Conceptional Unhealthy Diet: Potential Association with Altered Gut Microbiome Composition

Zhang¹,

Dong²,

Sun³

et al. 2019

Kidney Blood Press Res

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Background/Aims: Paternal exposure to adverse environmental conditions can act on offspring’s phenotype and influence offspring’s later life disease risk. Our study was designed to examine the effect of feeding male rats before mating a high-fat, high-sucrose and high-salt diet (HFSSD) over two generations (F0 and F1) on their offspring’s (F2) liver function and gut microbiome composition. Methods: Male F0 rats and male F1 rats were fed either control diet or HFSSD before mating. Liver function of F2 offspring was investigated, and their gut microbiome composition was analyzed by 16S rRNA gene sequencing in the F2 offspring of rats whose fathers and grandfathers were fed with control diet (CD) (F0CD+F1CD-F2 group) or HFSSD prior to mating (F0HD+F1HD-F2 group). Results: F2 offspring had higher serum aspartate aminotransferase activity (female, p < 0.05 and male, p < 0.01 respectively) compared with control. Shannon indexes of gut microbiota indicated a significantly higher diversity in the female F0HD+F1HD-F2 as compared to F0CD+F1CD-F2 female offspring (p < 0.01). The dominant phyla of all the groups were Bacteroidetes, Firmicutes and Proteobacteria. There were significant differences in gut bacterial community composition at phyla and genus level between the F0CD+F1CD-F2 and F0HD+F1HD-F2. Furthermore, the variation in the relative abundance (percentage) of bacterial genus in the F2 offspring was associated with liver function alterations induced by a paternal pre-conceptional unhealthy diet. Male F0HD+F1HD-F2 offspring had higher serum cholesterol, high density lipoproteins as well as low density lipoproteins concentrations compared to the corresponding male control rats. Conclusion: Taken together, our findings suggested that a paternal pre-conceptional unhealthy diet predisposes the offspring to mild liver function alterations and alterations of gut microbiota in later life. Effects on lipids were sex-specific and only seen in male offspring.

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Section: Discussionmentioning

confidence: 99%

“…Several studies showed that also paternal nutritional factors, in particular during maturation of the sperm, may alter the epigenome and the phenotype of the offspring [27-30]. …”

Section: Introductionmentioning

confidence: 99%

Paternal Programming of Liver Function and Lipid Profile Induced by a Paternal Pre-Conceptional Unhealthy Diet: Potential Association with Altered Gut Microbiome Composition

Zhang¹,

Dong²,

Sun³

et al. 2019

Kidney Blood Press Res

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“…Currently, the pharmaceutical industry is already speculating on selling dietary supplements to improve (sperm) health. While some evidence exists in animal models [105][106][107], clinical efficacy of the use of supplements in men-and especially on the improvement of his offspring health-has not been proven yet. This is another important reason why human studies are urgently needed.…”

Section: Public Health Implications and Precautionsmentioning

confidence: 99%

Transgenerational epigenetic effects from male exposure to endocrine-disrupting compounds: a systematic review on research in mammals

et al. 2020

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Assessing long-term health effects from a potentially harmful environment is challenging. Endocrine-disrupting compounds (EDCs) have become omnipresent in our environment. Individuals may or may not experience clinical health issues from being exposed to the increasing environmental pollution in daily life, but an issue of high concern is that also the non-exposed progeny may encounter consequences of these ancestral exposures. Progress in understanding epigenetic mechanisms opens new perspectives to estimate the risk of man-made EDCs. However, the field of epigenetic toxicology is new and its application in public health or in the understanding of disease etiology is almost non-existent, especially if it concerns future generations. In this review, we investigate the literature on transgenerational inheritance of diseases, published in the past 10 years. We question whether persistent epigenetic changes occur in the male germ line after exposure to synthesized EDCs. Our systematic search led to an inclusion of 43 articles, exploring the effects of commonly used synthetic EDCs, such as plasticizers (phthalates and bisphenol A), pesticides (dichlorodiphenyltrichloroethane, atrazine, vinclozin, methoxychlor), dioxins, and polycyclic aromatic hydrocarbons (PAHs, such as benzo(a)pyrene). Most studies found transgenerational epigenetic effects, often linked to puberty-or adult-onset diseases, such as testicular or prostate abnormalities, metabolic disorders, behavioral anomalies, and tumor development. The affected epigenetic mechanisms included changes in DNA methylation patterns, transcriptome, and expression of DNA methyltransferases. Studies involved experiments in animal models and none were based on human data. In the future, human studies are needed to confirm animal findings. If not transgenerational, at least intergenerational human studies and studies on EDCinduced epigenetic effects on germ cells could help to understand early processes of inheritance. Next, toxicity tests of new chemicals need a more comprehensive approach before they are introduced on the market. We further point to the relevance of epigenetic toxicity tests in regard to public health of the current population but also of future generations. Finally, this review sheds a light on how the interplay of genetics and epigenetics may explain the current knowledge gap on transgenerational inheritance.

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“…Epigenetic mechanisms are well known in feto-maternal pathophysiology. Environmental factors such as micro- and macronutrients even of the father [ 6 ] but also psychological factors such as stress during pregnancy [ 7 , 8 ] induce these epigenetic alterations. In other words, changeable environmental factors play a key role in inducing these disease-related epigenetic alterations in the placenta and elsewhere in the offspring's body.…”

mentioning

confidence: 99%

“…This makes this area of research so important given the often frustrating lack of promising therapeutic options if for example pure genetic reasons cause recurrent pregnancy loss. Even in the case that the yet unknown potential environmental causes leading to placental CREB5 hypomethylation are difficult to manipulate, treatment of mothers with methyl group donors such as folate [ 6 ] might be a treatment option. This needs to be addressed in further studies.…”

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confidence: 99%

Epigenetics of recurrent pregnancy loss

Hocher

2018

EBioMedicine

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Folate treatment of pregnant rat dams abolishes metabolic effects in female offspring induced by a paternal pre-conception unhealthy diet

Abstract: Folate treatment of pregnant dams restores effects on female offspring's glucose metabolism induced by pre-conception male founder HFSSD.

Cited by 22 publications

References 52 publications

Paternal Programming of Liver Function and Lipid Profile Induced by a Paternal Pre-Conceptional Unhealthy Diet: Potential Association with Altered Gut Microbiome Composition

Paternal Programming of Liver Function and Lipid Profile Induced by a Paternal Pre-Conceptional Unhealthy Diet: Potential Association with Altered Gut Microbiome Composition

Transgenerational epigenetic effects from male exposure to endocrine-disrupting compounds: a systematic review on research in mammals

Epigenetics of recurrent pregnancy loss

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