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A fathers' age & lifestyle associated with birth defects

Increasingly, research is showing an association between birth defects and a father's age, his alcohol use and other environmental factors, say researchers at Georgetown University Medical Center. These defects result from epigenetic (or 'outside of the genome') alterations that can potentially affect continuing generations.

The study, published in the American Journal of Stem Cells, suggest both parents contribute to the health status of their offspring a common sense conclusion which science is only now beginning to demonstrate, says the study's senior investigator, Joanna Kitlinska PhD, an associate professor in biochemistry, and molecular and cellular biology.
"We know the nutritional, hormonal and psychological environment provided by the mother permanently alters organ structure, cellular response and gene expression in her offspring. But our study shows the same thing to be true with fathers his lifestyle, and how old he is, can be reflected in molecules that control gene function. In this way, a father can affect not only his immediate offspring, but future generations as well."

Joanna B Kitlinska PhD, Associate Professor, Biochemistry, Molecular and Cellular Biology, Georgetown University Medical Center, Washington D.C., USA

A newborn can be diagnosed with fetal alcohol spectrum disorder (FASD), even though the mother has never consumed alcohol. Kitlinska explains: "Up to 75 percent of children with FASD have biological fathers who are alcoholics, suggesting that preconceptual paternal alcohol consumption negatively impacts their offspring."

The report reviews evidence, human and animal, linking fathers and inheritable epigenetic traits. Here are the findings from the multiple studies reviewed:

Father's advanced age correlates with elevated rates of schizophrenia, autism, and birth defects in his children

A father's limited diet during his pre-adolescence is linked to reduced risk of cardiovascular death in his children and grandchildren

Father's obesity is linked to enlarged fat cells, disturbed metabolic regulation, diabetes, obesity and brain cancers in his children

Psychosocially stressed fathers link to defective behavior traits in their offspring

Paternal alcohol abuse leads to lower birth weight, reduction in overall brain size and impaired cognitive function in his children.

"This new field of inherited paternal epigenetics needs to be organized into clinically applicable recommendations for lifestyle alternations. To really understand the epigenetic influences on a child, we need to study the interplay between maternal and paternal effects, and not consider each in isolation."

Joanna B Kitlinska PhD

Historically, research into congenital defects has focused on maternal impacts on the fetal genome during gestation and prenatal periods. However, recent findings have sparked interest in epigenetic alterations of paternal genomes and its effects on offspring. This emergent field focuses on how environmental influences can epigenetically alter gene expression and ultimately change the phenotype and behavior of progeny. There are three primary mechanisms implicated in these changes: DNA methylation, histone modification, and miRNA expression. This paper provides a summary and subsequent review of past research, which highlights the significant impact of environmental factors on paternal germ cells during the lifetime of an individual as well as those of future generations. These findings support the existence of transgenerational epigenetic inheritance of paternal experiences. Specifically, we explore epidemiological and laboratory studies that demonstrate possible links between birth defects and paternal age, environmental factors, and alcohol consumption. Ultimately, our review highlights the clinical importance of these factors as well as the necessity for future research in the field.

Keywords: Transgenerational effects, paternal preconception exposures, epigenetics

Study co-authors are: Jonathan Day, MS, Soham Savani, MS, Ben Krempley, MS, and Matthew Nguyen, MS, graduates of Georgetown's Special Masters Program in Physiology.

> This study was supported in part by National Institutes of Health grants (1R01CA123211, 1R03CA178809, R01CA197964 and 1R21CA198698).

About Georgetown University Medical Center
Georgetown University Medical Center (GUMC) is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through MedStar Health). GUMC's mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis -- or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing & Health Studies, both nationally ranked; Georgetown Lombardi Comprehensive Cancer Center, designated as a comprehensive cancer center by the National Cancer Institute; and the Biomedical Graduate Research Organization, which accounts for the majority of externally funded research at GUMC including a Clinical and Translational Science Award (UL1TR001409-01) from the National Institutes of Health.

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Jun 14, 2017   Fetal Timeline   Maternal Timeline   News   News Archive

A recent literature review reveals how a father's mental as well as physical state
contributes heavily to heritable traits in his children and grandchildren.
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