title: Stress-induced perinatal and transgenerational epigenetic programming of brain development and mental health.
abstract: Research efforts during the past decades have provided intriguing evidence suggesting that stressful experiences during pregnancy exert long-term consequences on the future mental wellbeing of both the mother and her baby. 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. Epigenetic mechanisms, such as miRNA expression, DNA methylation, and histone modifications are prone to changes in response to stressful experiences and hostile environmental factors. Altered epigenetic regulation may potentially influence fetal endocrine programming and brain development across several generations. Only recently, however, more attention has been paid to possible transgenerational effects of stress. In this review we discuss the evidence of transgenerational epigenetic inheritance of stress exposure in human studies and animal models. We highlight the complex interplay between prenatal stress exposure, associated changes in miRNA expression and DNA methylation in placenta and brain and possible links to greater risks of schizophrenia, attention deficit hyperactivity disorder, autism, anxiety- or depression-related disorders later in life. Based on existing evidence, we propose that prenatal stress, through the generation of epigenetic alterations, becomes one of the most powerful influences on mental health in later life. The consideration of ancestral and prenatal stress effects on lifetime health trajectories is critical for improving strategies that support healthy development and successful aging.
authors.affiliation: Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, 4401 University Drive, Lethbridge, AB, Canada T1K 3M4; Department of Biological Sciences, University of Lethbridge, 4401 University Drive, Lethbridge, AB, Canada T1K 3M4.
authors.forename: Olena
authors.initials: O
authors.lastname: Babenko
authors.affiliation: Department of Biological Sciences, University of Lethbridge, 4401 University Drive, Lethbridge, AB, Canada T1K 3M4.
authors.forename: Igor
authors.initials: I
authors.lastname: Kovalchuk
authors.affiliation: Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, 4401 University Drive, Lethbridge, AB, Canada T1K 3M4.
authors.forename: Gerlinde A S
authors.initials: GA
authors.lastname: Metz
mesh_terms: D000818:Animals; D001921:Brain / Q000254:growth & development* / Q000503:physiopathology; D044127:Epigenesis, Genetic; D005260:Female; D047109:Fetal Development / Q000235:genetics / Q000502:physiology; D006801:Humans; D001523:Mental Disorders / Q000235:genetics* / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D013315:Stress, Psychological / Q000235:genetics* / Q000503:physiopathology
keywords: Aging; Anxiety; Brain development; DNA methylation; Depression; Epigenetics; Gestation; Glucocorticoids; Maternal health; Maternal stress; Mental health; Neurological disease; Newborn health; Perinatal programming; Pregnancy; Prenatal stress; Psychiatric disease; Small non-coding RNA; Stress resilience; Stress vulnerability; Transgenerational epigenetic inheritance; microRNA