From Diet To DNA: How Fathers' Eating Habits Might Shape Daughters' Heart Health

Like father, like daughter - There goes the saying. Now it's found that men with unhealthy, high-cholesterol diets may increase the risk of cardiovascular disease (CVD) in their daughters, according to a University of California, Riverside-led mouse study. This research, published in JCI Insight, is the first to show such effects specifically in female offspring, according to ScienceDaily.

CVD is a group of disorders affecting the heart and blood vessels and is the leading cause of death worldwide. Hypertension, or high blood pressure, is a major risk factor for CVD. In 2022, nearly 703,000 people in the United States died from heart disease, accounting for one in every five deaths.

The study focused on atherosclerosis, a chronic inflammatory disease that leads to CVD. Atherosclerosis involves plaque buildup in artery walls, which narrows arteries and restricts blood flow and oxygen supply to vital organs. The researchers found that male mice fed a high-cholesterol diet had altered small RNA molecules in their sperm. These changes affected early gene expression in mouse embryonic stem cells.

"Men who plan to have children should consider eating a healthy, low-cholesterol diet and reducing their own CVD risk factors," said Changcheng Zhou, professor of biomedical sciences at UCR and lead author of the study. "These factors appear to affect their sperm in influencing the health of their female offspring."

The researchers used genetically engineered male mice fed a high-cholesterol diet to induce hyperlipidemia. These males were then mated with females on a regular diet. Their offspring were also fed a low-cholesterol diet. The female offspring showed 2-3-fold increases in atherosclerosis compared to controls.

Zhou noted that most studies focus on maternal factors affecting offspring health. "The impact of paternal exposures on offspring health has been largely overlooked," he said. This study highlights the importance of considering paternal influences on chronic disease development.

Sperm contains numerous small non-coding RNA molecules crucial for gene regulation and cellular processes. When these are modified by environmental factors like diet, they can significantly alter biological functions. The study found that small RNA molecules in sperm from high-cholesterol-fed mice underwent changes that could influence gene expression early in development.

To analyze sperm small RNA molecules, researchers employed PANDORA-seq technology developed at UCR.

"It had been previously thought that sperm contribute only their genome during fertilization," Zhou explained. "However, recent studies have shown that environmental exposures can alter RNA in sperm to mediate intergenerational inheritance."

The researchers are unsure why only female offspring are affected by CVD under these conditions. Zhou hopes this study will encourage further investigations into how paternal exposures impact cardiovascular health in human offspring.

"Our study contributes to understanding the etiology of chronic diseases originating from parental exposures," Zhou said. He emphasized the need for more research on paternal influences on offspring health.