Several studies have suggested that various parental exposures affect offspring’s cardiovascular health. However, the specific mechanisms, particularly the influence of paternal cardiovascular disease (CVD) risk factors on offspring cardiovascular health, remain elusive.
A new study from the University of California, Riverside, explores how paternal hypercholesterolemia affects offspring atherosclerosis development. The study found that fathers on unhealthy, high-cholesterol diets can cause an increased risk of CVD in their daughters.
This is the first study that found this result only in female offspring.
Previously, it was thought that sperm contribute only their genome during fertilization. However, recent studies suggested that other factors, such as unhealthy diet, environmental toxicants, and stress, can alter the RNA in sperm to mediate intergenerational inheritance.
Changcheng Zhou, a professor of biomedical sciences in the School of Medicine and the study’s lead author, said, “Men who plan to have children should consider eating a healthy, low-cholesterol diet and reducing their CVD risk factors. These factors appear to affect the sperm and influence the health of their female offspring. Our study suggests the sperm passes this information to the next generation.”
Scientists mainly focused on atherosclerosis, a complex disease characterized by the accumulation of cholesterol in large arteries, leading to plaque development in the intimal layer of the artery. Despite significant advances in diagnoses and treatments, atherosclerotic cardiovascular disease (CVD) is still the leading cause of mortality and morbidity worldwide.
Sperm contains many tiny RNA molecules that help control genes and other cell activities. If these RNA molecules are changed, their roles in the body can shift greatly.
Scientists studied sperm small RNA using the PANDORA-seq method. They found that in mice fed a high-cholesterol diet, these tiny RNA molecules in sperm change. These changes can impact how genes are expressed in early mouse embryonic stem cells.
Zhou explained that most studies have focused on the effects of maternal factors on offspring health. He said the impact of paternal exposures on offspring health has been largely overlooked.
“It is challenging to study the impact of parental exposures on chronic disease development in their offspring because the experiments, in general, are time-consuming and require more resources and careful planning.”
It remains elusive why only female offspring are affected with CVD. In their experiment, scientists fed mice a high-cholesterol diet, which caused them to have hyperlipidemia, a disorder that, if left untreated, can lead to heart disease and stroke.
These mice were bred with female mice on a normal, low-cholesterol diet, and their offspring were also given a low-cholesterol diet. Despite this, the female offspring had 2-3 times more atherosclerosis.
“Our study contributes to understanding the etiology of chronic diseases originating from parental exposures,” Zhou said. “We hope our findings stimulate investigations of the impact of paternal exposures on offspring cardiovascular health in humans.”
Journal Reference:
- Rebecca Hernandez, Xiuchun Li et al. Paternal hypercholesterolemia elicits sex-specific exacerbation of atherosclerosis in offspring. JCI Insight. DOI: 10.1172/jci.insight.179291