Germ Cell Origins of Posttraumatic Stress Disorder Risk: The Transgenerational Impact of Parental Stress Experience

Rodgers, Ali B.; Bale, Tracy L.

doi:10.1016/j.biopsych.2015.03.018

Cited by 72 publications

(40 citation statements)

References 116 publications

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“…Certainly, evidence in humans also suggests a strong correlation between fetal testosterone levels and steroidogenic activity with neurodevelopmental disease risk and adult cognitive and behavioral stress reactivity, supporting the importance of the processes involved in establishing the sexually dimorphic Figure 3 Sex and gender differences across the life span. Based on preclinical and clinical research: (a) maternal and paternal life experience can impact fetal programming and offspring behavior in a sex-specific manner (Bale and Epperson, 2015;Rodgers and Bale, 2015). (b) Postpartum depression is associated with behavioral differences in female and male infants and young children (Azak, 2012;Kingston et al, 2012).…”

Section: Sex Differences Related To Sex Chromosomes and Hormones And mentioning

confidence: 99%

Sex as a Biological Variable: Who, What, When, Why, and How

Bale

Epperson

2016

Neuropsychopharmacol

120

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The inclusion of sex as a biological variable in research is absolutely essential for improving our understanding of disease mechanisms contributing to risk and resilience. Studies focusing on examining sex differences have demonstrated across many levels of analyses and stages of brain development and maturation that males and females can differ significantly. This review will discuss examples of animal models and clinical studies to provide guidance and reference for the inclusion of sex as an important biological variable relevant to a Neuropsychopharmacology audience.

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Section: Sex Differences Related To Sex Chromosomes and Hormones And mentioning

confidence: 99%

Sex as a Biological Variable: Who, What, When, Why, and How

Bale

Epperson

2016

Neuropsychopharmacol

120

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“…Germ cell epigenetic marks, vulnerable to environmental stimuli and capable of directing profound developmental change, may mediate the effects of parental lifetime environmental exposures on offspring behavior and physiology (9,10). Rodent models examining paternal transmission have identified epigenetic signatures in mature sperm as possible substrates of transgenerational programming, namely patterns of retained histone modifications, DNA methylation, and/or populations of small noncoding RNAs (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21).…”

mentioning

confidence: 99%

Transgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal stress

Rodgers

Morgan

Leu

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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628

543

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Epigenetic signatures in germ cells, capable of both responding to the parental environment and shaping offspring neurodevelopment, are uniquely positioned to mediate transgenerational outcomes. However, molecular mechanisms by which these marks may communicate experience-dependent information across generations are currently unknown. In our model of chronic paternal stress, we previously identified nine microRNAs (miRs) that were increased in the sperm of stressed sires and associated with reduced hypothalamic-pituitaryadrenal (HPA) stress axis reactivity in offspring. In the current study, we rigorously examine the hypothesis that these sperm miRs function postfertilization to alter offspring stress responsivity and, using zygote microinjection of the nine specific miRs, demonstrated a remarkable recapitulation of the offspring stress dysregulation phenotype. Further, we associated long-term reprogramming of the hypothalamic transcriptome with HPA axis dysfunction, noting a marked decreased in the expression of extracellular matrix and collagen gene sets that may reflect an underlying change in blood-brain barrier permeability. We conclude by investigating the developmental impact of sperm miRs in early zygotes with single-cell amplification technology, identifying the targeted degradation of stored maternal mRNA transcripts including sirtuin 1 and ubiquitin protein ligase E3a, two genes with established function in chromatin remodeling, and this potent regulatory function of miRs postfertilization likely initiates a cascade of molecular events that eventually alters stress reactivity. Overall, these findings demonstrate a clear mechanistic role for sperm miRs in the transgenerational transmission of paternal lifetime experiences.transgenerational | epigenetic | stress | microRNA | paternal

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“…Thus, in male mice the traumatic stress during spermatogenesis induced an expression of certain miRNAs, which also persisted in the zygote that led to changes in behavior and metabolism in the offspring [61,62]. This miRNA, being isolated and then introduced into normal zygote, caused the same changes in born offspring [63,64]. In the primordial stem cells populating gonads of the embryos prenatally exposed to vinclozolin, the endocrine disregulator, there were changes in synthesis of a number of miRNAs that regulate cell differentiation [65].…”

Section: E R T I C a L D A M A G E I N D U C E D B Y I O N I Z I N mentioning

confidence: 85%

Chernobyl and Fukushima Nuclear Accidents

Glazko¹,

Zybailov²,

Glazko³

2016

S-h. biol.

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A b s t r a c tIn the review, our own studies of increased ionizing radiation effects on agricultural animals (nutria, rabbits, pigs, cattle) and small rodents of bio-indicator species after Chernobyl NPP accident are compared with published data of human populations' survey after the accidents at Chernobyl and Fukushima nuclear power plants. Similarity is noted of main targets for ionizing radiation (the cardiovascular system and kidneys) identified in humans and agricultural animals. Effects of ionizing radiation and post-traumatic syndromes are also comparable. Biomarkers of damages caused by ionizing radiation are considered. Differences in the estimates of the thyroid gland papillary carcinoma frequency after nuclear accidents at Chernobyl and Fukushima NPPs are discussed. Apparently, this inconsistency is mainly due to genogeographic factors, iodine deficit in geochemical province, and natural selection affecting number of generations in the populations from naturally radioactive provinces or under enhanced radionuclide pollution after technological accidents (T.I. Bogdanova et al., 2015; V.M. Drozd et al., 2015; M.B. Zimmermann, V. Galetti, 2015). A nonlinear dependency of biological effects of irradiation in the low dose range was analyzed with its possible mechanisms discussed (i.e. damage accumulation until the level necessary to induce DNA reparation, changes in young to old cell proportion in the populations, mitochondrial dysfunction) (E. Markievicz et al., 2015). A concept of «horizontal» and «vertical» effects of ionizing radiation on biological objects is introduced. It was shown that in different species of rodents (Microtus arvalis, Clethrionomys glareolus), and in the laboratory mice of C57BL/6, ÑÑ57W/Mv, and BALB/c lines the irradiation of bone marrow cells induced an increase of only those cytogenetic anomalies, in comparison of control groups, the increased variability of which was typical for the studied objects in a relatively clean areas. The main and, apparently, underestimated vertical consequence of raised ionizing radiation is the decrease in reproductive success of irradiated animals. Importantly, a transgenerational transmission of post-traumatic syndrome and its mechanisms, including transmission of microRNAs, the mediators of the stress response, through the spermatozoa (K. Gapp et al., 2014), changes in microbiota of parents and their children, as well as cultural inheritance are involved to explain a complexity of observed radiobiological effects and their inheritance revealed in recent years.

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Germ Cell Origins of Posttraumatic Stress Disorder Risk: The Transgenerational Impact of Parental Stress Experience

Cited by 72 publications

References 116 publications

Sex as a Biological Variable: Who, What, When, Why, and How

Sex as a Biological Variable: Who, What, When, Why, and How

Transgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal stress

Chernobyl and Fukushima Nuclear Accidents

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