Paternal Psychological Stress Reprograms Hepatic Gluconeogenesis in Offspring

Wu, Ling; Lu, Yan; Jiao, Yang; Liu, Bin; Li, Shangang; Li, Yao; Xing, Fengying; Chen, Dongbao; Liu, Xing; Zhao, Jiejie; Xiong, Xuelian; Gu, Yuchao; Lu, Jieli; Chen, Xuejin; Li, Xiaoying

doi:10.1016/j.cmet.2016.01.014

Cited by 118 publications

(113 citation statements)

References 39 publications

(31 reference statements)

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“…Gestational undernutrition is particularly prominent in adolescence with maternalfetal competition for energy and nutrients that remain essential for a girl's own continued growth 33 . It is associated with increased risk of neonatal mortality, preterm birth, small for gestational age babies, and low birth weight 34 . The effects extend to the postnatal period with compromised antenatal breast development reducing breast milk quality and quantity 35 and the establishment of attachment bonds 36,37 .…”

Section: Early Parenthood and Its Consequencesmentioning

confidence: 99%

Adolescence and the next generation

Patton

Olsson

Skirbekk

et al. 2018

Nature

270

228

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Adolescent growth and social development shape the early development of offspring from preconception through to the post-partum period through distinct processes in males and females. At a time of great change in the forces shaping adolescence, including the timing of parenthood, investments in today’s adolescents, the largest cohort in human history, will yield great dividends for future generations.

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Section: Early Parenthood and Its Consequencesmentioning

confidence: 99%

Adolescence and the next generation

Patton

Olsson

Skirbekk

et al. 2018

Nature

270

228

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“…3f). miRNA expression can be regulated by DNA methylation [33]; however, integration of the genome-wide DNA methylation and RNA-seq data in control and LP normal mammary tissues did not reveal any statistically significant changes in DNA methylation patterns in promoter regions of differentially expressed miRNAs.…”

Section: Resultsmentioning

confidence: 99%

Paternal malnutrition programs breast cancer risk and tumor metabolism in offspring

et al. 2018

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BackgroundWhile 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.MethodsMale 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.ResultsWe 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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (10.1186/s13058-018-1034-7) contains supplementary material, which is available to authorized users.

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“…MicroRNAs must now be considered as long-term regulators of offspring behavior and stress response. These findings are in addition to evidence of the involvement of microRNAs in paternal diet-linked modification of offspring metabolism and obesity [34–36]. Of course, we cannot exclude the involvement of other subspecies of sncRNAs.…”

Section: Paternal Stress Influences Male Offspring Anxiety and Depresmentioning

confidence: 68%

Transgenerational paternal transmission of acquired traits: stress-induced modification of the sperm regulatory transcriptome and offspring phenotypes

Pang

Short

Bredy

et al. 2017

Current Opinion in Behavioral Sciences

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In recent years, it has become evident that pre-conceptual exposure of males to various environmental factors induces epigenetic changes in sperm, which can mediate the transmission of acquired traits in their offspring. The most thoroughly examined paternal exposures involve stress and elevated corticosterone, which have been shown to modulate offspring phenotypes in a manner that is relevant to predisposition to brain disorders, and psychiatric illness in particular. Recent seminal studies have demonstrated that key epigenetic information transmitted via the paternal germline involves small non-coding (snc) RNA transcripts such as microRNAs. Following fertilisation, these sncRNAs appear to regulate development so as to modify the phenotype of the offspring. Understanding the mechanisms involved in such transgenerational effects may facilitate future screening of human sperm for ‘epigenetic health’ and the tailoring of therapeutic interventions according to genetic and epigenetic contributions to illness.

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Paternal Psychological Stress Reprograms Hepatic Gluconeogenesis in Offspring

Cited by 118 publications

References 39 publications

Adolescence and the next generation

Adolescence and the next generation

Paternal malnutrition programs breast cancer risk and tumor metabolism in offspring

Transgenerational paternal transmission of acquired traits: stress-induced modification of the sperm regulatory transcriptome and offspring phenotypes

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