Stress-induced perinatal and transgenerational epigenetic programming of brain development and mental health

Babenko, Olena Mykolaivna; Kovalchuk, Igor; Metz, Gerlinde A. S.

doi:10.1016/j.neubiorev.2014.11.013

Cited by 435 publications

(317 citation statements)

References 318 publications

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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.

640

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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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.

640

543

View full text Add to dashboard Cite

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“…Maternal intake of steroid hormones (Marciniak et al 2011), maternal depression (O'Connor et al 2014, and maternal anxiety (Kane et al 2014) have been shown to alter maternal glucocorticoid levels, with a high correlation between maternal and fetal plasma glucocorticoids (Provencal and Binder 2015). In addition to affecting birth outcomes, stressful experiences in utero or during early life may also increase the risk of neurodevelopmental and behavioral disorders later in life due to alterations in epigenetic regulation (Babenko et al 2015).…”

Section: Epigenetic Mechanismsmentioning

confidence: 99%

Life Course Health Development Outcomes After Prematurity: Developing a Community, Clinical, and Translational Research Agenda to Optimize Health, Behavior, and Functioning

Msall

Sobotka

Dmowska

et al. 2017

Handbook of Life Course Health Development

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Long-term survival for infants born extremely prematurely (<28 weeks of gestation) and extremely low birth weight (<1000 g) has increased dramatically due to obstetrical and neonatal advances. However, poverty, inequality, and resulting health disparities are significant contributors to women who give birth to preterm infants and also impact their children’s healthy development and education. While the vast majority of survivors of extreme prematurity do not have the most severe forms of neurodevelopmental disability (i.e., cerebral palsy, blindness, sensorineural hearing loss >55 dB, and intellectual disability), half of survivors can be expected to require special education services at kindergarten entry and during their school years. In addition, there are also high rates of health disparities in the prevalence of preterm birth across the spectrum of gestations including very preterm (28–31 weeks), moderate preterm (32–33 weeks), and late preterm births (34–36 weeks). Life course health development offers a valuable framework for examining how complex medical and social adversities that impact a mother’s health can also impact their child’s health and developmental trajectories. A better understanding of the cumulative impact of protective factors and other buffers that can support prenatal and postnatal parental and child health will provide important insights into how to promote greater resiliency and optimal health development. This population-based information can provide ongoing data for thriving developmental health trajectories for vulnerable preterm survivors with respect to physical, behavioral, and social health outcomes. Though premature infants who receive comprehensive early intervention and preschool educational supportive services have improved outcomes at kindergarten entry, school-age survivors, even those escaping major neurodevelopmental diagnoses, have challenges which impact attention, behavioral regulation, academic achievement, and social skills compared to their full-term peers. Unfortunately, many essential services that can contribute to better outcomes are unnecessarily fragmented and not systematically implemented to provide preventive interventions that optimize health, learning, executive function, social, and adaptive competencies. These cumulative medical, developmental, and social risks among preterm survivors adversely impact long-term adult physical and behavioral health, educational attainment, and social participation. In order to address these disparities, more precise, population-based, health development interventions aimed at optimizing physical and behavioral health, educational achievement, and adaptive competencies will be required. We recommend research strategies to inform our efforts for improving life course outcomes.

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“…In experimental animals early life stress increases stress vulnerability through BDNF (brain-derived neurotrophic factor) gene epigenetic changes with decreased levels of acetylated histone H3 and H4 [359]. Recent human epidemiological and animal studies indicate that stressful experiences in utero or during early life may increase the risk of neurological and psychiatric disorders, arguably via altered epigenetic regulation and transgenerational epigenetic inheritance (for review see [360]). …”

Section: Mental Stressmentioning

confidence: 99%

The Genetic and Epigenetic Basis Involved in the Pathophysiology of ASD: Therapeutic Implications

Carrascosa-Romero¹,

Cabo²

2017

Autism - Paradigms, Recent Research and Clinical Applications

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The prevalence of autism has increased in an exponential way in the past few years. Many monogenetic mutations as well as copy number variants and single nucleotide polymorphisms have been associated with autism spectrum disorders (ASD), a large proportion of which occur in genes associated with synaptogenesis and synaptic function. However, the increase in appearance of genetic alterations does not explain the etiology of an elevated number of ASD cases. Recent research is now focusing on the role of environmental/epigenetic factors, which by themselves and/or in combination with classical genetic factors, may be the root cause of a large number of ASDs. In this chapter we review the current literature regarding the epigenetic changes involved in ASD, including their possible mechanisms of action such as oxidative stress, altered fatty acid metabolism, mitochondrial dysfunction, DNA methylation and histone methylation (via the one-carbon metabolism cycle), histone variants, and ATP-dependent chromatin remodeling. We discuss possible new biochemical markers related to autism as well as new lines of research for therapeutic targets.

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Stress-induced perinatal and transgenerational epigenetic programming of brain development and mental health

Cited by 435 publications

References 318 publications

Transgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal stress

Transgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal stress

Life Course Health Development Outcomes After Prematurity: Developing a Community, Clinical, and Translational Research Agenda to Optimize Health, Behavior, and Functioning

The Genetic and Epigenetic Basis Involved in the Pathophysiology of ASD: Therapeutic Implications

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