Obese male mice and normal weight female mice produce female pups that are overweight from birth through childhood, and have delayed development of their breast tissue as well as increased rates of breast cancer.
These findings, published June 24 online in Scientific Reports by researchers at Georgetown Lombardi Comprehensive Cancer Center, come from one of the first animal studies to examine the impact of paternal obesity on future generations’ cancer risk.
Obesity can run in families, and the same is true for some breast cancers. Maternal obesity is believed to influence both conditions in humans—a woman who is heavy in pregnancy can produce larger babies, and when those big babies grow to adulthood, they may have increased risk of breast cancer. While much of the focus has been on the maternal side, few if any studies have looked at the influence of dad’s obesity on his offspring’s cancer risk.
The researchers found evidence that obesity changes the microRNA (miRNA) signature—epigenetic regulators of gene expression—in both the dad’s sperm and the daughter’s breast tissue, suggesting that miRNAs may carry the epigenetic information from obese dads to their daughters. The miRNAs identified regulate insulin receptor signaling, which is linked to alterations in body weight, and other molecular pathways that are associated with cancer development such as the hypoxia signaling pathway.
“This study provides evidence that, in animals, a father’s body weight at the time of conception affects both the daughter’s body weight both at birth and in childhood, as well as her risk of breast cancer later in life,” says the study’s lead investigator, Sonia de Assis, PhD, an assistant professor in the department of oncology at Georgetown Lombardi.
“Of course our study was done in mice, but it recapitulates recent findings in humans which show that obese men have significant epigenetic alterations in their sperm compared to lean men. Our animal study suggests that those epigenetic alterations in sperm may have consequences for next generation cancer risk”
The next step, de Assis says, is to see if the same associations regarding breast cancer risk hold not just for mice but for humans, too.