Seeds of Disease sown before Birth

Fetal stress disrupts the way genes are transmitted

http://www.faseb.org

New research in The FASEB Journal suggests that a disruption of genetic imprinting often happens prenatally, implicating fetal stressors as long-term risk factor for chronic disease

Bethesda, MD — If you think stress is killing you, you may be right, but what you don’t know is that stress might have harmed your health even before you were born. In a new report appearing in the August 2013 issue of The FASEB Journal, Harvard researchers find that epigenetic disruptions, which are associated with chronic disease later in life, are already common at birth.

Possibly, these aberrations result from stressors in the intrauterine environment (e.g. maternal smoking, maternal diet, or high levels of endocrine-disrupting chemicals). This finding supports the belief that seeds of disease are sown before birth, increasing the importance of optimal prenatal care.

“This study may help us understand whether epigenetic mechanisms contribute to chronic disease susceptibility already prior to birth,” said Karin Michels, Sc.D., Ph.D., study author from Harvard Medical School in Boston, Mass. “We are currently exploring which stressors during prenatal life may contribute to these epigenetic disruptions.”

To make this discovery, Michels and colleagues examined the expression pattern of imprinted genes important for growth and development. Researchers analyzed the parental expression pattern in the cord blood and placenta of more than 100 infants and followed up this analysis with methylation and expression studies.

The results lent credence to the emerging theme that susceptibility to disease may indeed originate in utero. Additionally, this research showed that a high degree of disruption occurred during the imprinting of a gene called IGF2, which was expressed from both alleles in the cord blood of 22 percent of study subjects. Loss of imprinting of IGF2 has been associated with several cancers, including Wilms Tumor, colorectal and breast cancer and childhood disorders such as Beckwith-Wiedemann Syndrome.

“For a long time, doctors have considered fetal stress as a symptom of serious familial disease,” said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. “Now, we see that fetal stress is in and of itself a long-term risk factor for chronic disease: it changes the way we inherit genes from our parents.”

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Further Readings of Interest

Epigenetic and genetic variation at the IGF2/H19 imprinting control region on 11p15.5 is associated with cerebellum weight.

http://www.ncbi.nlm.nih.gov/pubmed/?term=IGF2+autism

IGF2 is a paternally expressed imprinted gene with an important role in development and brain function. Allele-specific expression of IGF2 is regulated by DNA methylation at three differentially methylated regions (DMRs) spanning the IGF2/H19 domain on human 11p15.5. We have comprehensively assessed DNA methylation and genotype across the three DMRs and the H19 promoter using tissue from a unique collection of well-characterized and neuropathologically-dissected post-mortem human cerebellum samples (n = 106) and frontal cortex samples (n = 51). We show that DNA methylation, particularly in the vicinity of a key CTCF-binding site (CTCF3) in the imprinting control region (ICR) upstream of H19, is strongly correlated with cerebellum weight. DNA methylation at CTCF3 uniquely explains ~25% of the variance in cerebellum weight. In addition, we report that genetic variation in this ICR is strongly associated with cerebellum weight in a parental-origin specific manner, with maternally-inherited alleles associated with a 16% increase in cerebellum weight compared with paternally-inherited alleles. Given the link between structural brain abnormalities and neuropsychiatric disease, an understanding of the epigenetic and parent-of-origin specific genetic factors associated with brain morphology provides important clues about the etiology of disorders such as schizophrenia and autism.

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This entry was posted in Autism, Environment, Epigenetics, Genetics, Immune System, Inflammation, Neurology, Physiology, Schizophrenia. Bookmark the permalink.

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