Although we typically think the mother has a large impact on her child’s health, epigenetic research is beginning to suggest that a father’s behavior may also have a significant amount of influence. Recently, we posted a blog article on the epigenetic influence a father’s lifestyle has on his children, showing that both mothers and fathers contribute to their offspring’s health through epigenetic alterations. Other research has indicated that a father’s diet could impact his sperm epigenome and influence pregnancy outcomes. Adding even more evidence to the subject matter, a new study conducted by researchers at the Georgetown Lombardi Comprehensive Cancer Center researchers is one of the first mouse studies to assess the effect of a father’s obesity on the cancer risk of his offspring. Ultimately, they found that paternal overweight is associated with increased breast cancer risk in daughters in a mouse model. The study was published in Scientific Reports.
The team of scientists believes that they have revealed evidence that attributes paternal obesity to several detrimental consequences for their daughters via epigenetics. They found that offspring of male mice that were fed a controlled high-fat diet tended to weigh more at birth. Paternal overweight near the time of conception was linked to epigenetic changes in the father’s germline. The microRNA (miRNA) signatures of the father’s sperm and his daughter’s breast tissue was changed as a result of overweight fathers, which suggests that the miRNAs might carry epigenetic information from the father to his daughter. In addition, they found that mammary gland development was altered and there was an increased risk of breast cancer in their daughters.
MicroRNAs are epigenetic regulators of gene expression. Previous research has shown that deregulation of miRNA expression is important in the formation of breast cancer. The miRNAs investigated in the study regulate insulin receptor signaling, a process connected to changes in body weight and additional molecular pathways linked to cancer, for example, the hypoxia signaling pathway.
The researchers reported that, “Compared with controls, [obesity-inducing diet] female offspring had a total of 39 differentially expressed miRNAs in their mammary glands, five of which were up-regulated and thirty-four down-regulated.” When they compared the daughter miRNA expression profiles to the father, they found similar alterations in both generations. Specifically, three particular miRNAs were down-regulated in the fathers’ sperm and the daughters’ mammary tissue.
Obesity and breast cancer are thought to run in families. Maternal obesity can contribute to larger babies and increase the child’s risk of developing breast cancer. Although research tends to focus on the role maternal overweight has on the children’s health, new evidence is finally assessing the father’s impact of being overweight.
“This study provides evidence that, in animals, a fathers’ body weight at the time of conception affects both their daughters’ body weight both at birth and in childhood as well as their risk of breast cancer later in life,” said Sonia de Assis, PhD, an assistant professor in the department of oncology at Georgetown Lombardi and the study’s lead author.
Their animal model recapitulates recent findings in humans that demonstrate that lean and obese men have varying epigenetic alterations in their sperm, noted de Assis. And these epigenetic changes may negatively affect the following generation’s risk of cancer. The next step is finding out if the results of this mouse study hold true for humans.
“Until we know about this association in men, we should stick to what we all know is good advice: women — and men — should eat a balanced diet, keep a healthy body weight and life-style not only for their own benefit but also to give their offspring’s the best chances of being healthy.”
Source: Fontelles, C.C., Carney, E., Clarke, J., Nguyen, N.M., Yin, C., Jin, L., Cruz, M.I., Ong, T.P., Hilakivi-Clarke, L., de Assis, S. (2016). Paternal overweight is associated with increased breast cancer risk in daughters in a mouse model. Scientific Reports, 6:28606.
Reference: Georgetown University Medical Center. In mice, daughters of overweight dads have altered breast tissue, higher cancer risk. EurekAlert. 24 Jun 2016. Web.