Researchers studying DNA from umbilical cord blood leukocytes found an association between paternal obesity and hypomethylation at the offspring’s insulin-like growth factor 2 (IGF2) gene.
Study findings indicate that aberrant low methylation at this differentially methylated region is linked to adverse outcomes, including higher risks for certain cancers.1 The research, published in BMC Medicine in 2013, suggests that fathers’ lifestyle factors could be passed onto their children by epigenetic mechanisms—a finding with potential public health implications regarding obesity’s global burden.
“I don’t think that we previously considered that the father could biologically contribute more to his offspring than the DNA in his sperm. Most research has focused on how the in-utero environment and health of the mother would impact development,” says study author Susan K. Murphy, PhD, associate professor in Obstetrics and Gynecology and chief, Division of Reproductive Sciences, Department of Obstetrics and Gynecology, at Duke University Medical Center, Durham, North Carolina. “This research and other emerging data are showing that the preconceptional health of the father, including his body mass index (BMI), are able to impact the status of his child’s DNA. This impact is not due to genetic changes, but rather to epigenetic shifts that determine how the child’s DNA is regulated.”
Murphy and colleagues studied blood leukocytes from 79 newborns’ umbilical cords. They obtained data about parental characteristics with standardized questionnaires and medical records, and they analyzed 2 differentially methylated regions (DMRs): the IGF2 DMR and the DMR upstream of the neighboring H19 gene (H19 DMR).1
They found that about 1 in 5 of the fathers had a BMI of 30 kg/m2 or higher. Although hypomethylation at the IGF2 DMR was linked to paternal obesity, the researchers didn’t find a significant association between paternal obesity and methylation patterns at the H19 DMR.1
The molecular mechanism behind the finding could be a hormonal difference between obese and non–obese parents, the researchers hypothesized.
“As a result, exposures to adverse lifestyle factors or poor or overnutrition during spermatogenesis may affect the reprogramming of methylation profiles at imprinted genes. Further research is necessary to confirm this hypothesis,” the investigators wrote.1
In a comment published in the same BMC Medicine issue called “Fat dads must not be blamed for their children’s health problems,” the authors noted the importance of taking an unbiased look at the big picture—considering the whole genome/epigenome/metabolome and involving all key genes and networks.2
1. Soubry A, Schildkraut JM, Murtha A, et al. Paternal obesity is associated with IGF2 hypomethylation in newborns: results from a Newborn Epigenetics Study (NEST) cohort. BMC Med. 2013;11:29.
2. Moore GE, Stanier P. Fat dads must not be blamed for their children's health problems. BMC Med. 2013;11:30.
3. Murphy SK, Itchon-Ramos N, Visco Z, et al. Cannabinoid exposure and altered DNA methylation in rat and human sperm. Epigenetics. 2018;13(12):1208-1221.
4. Levin ED, Hawkey AB, Hall BJ, et al. Paternal THC exposure in rats causes long-lasting neurobehavioral effects in the offspring. Neurotoxicol Teratol. April 24, 2019. Epub ahead of print.