A new animal study by a team at the Ohio State University suggests that a parent’s exposure to dirty air before conception may result in cardiac dysfunction in adult male offspring. The open-access paper is published in the Journal of the American Heart Association.

The study used an in vivo mouse model of preconception exposure to PM_2.5 to investigate the adverse cardiac effects on male offspring. The results revealed that the preconception period represents a “critical window” for the development of cardiac dysfunction in the offspring at adulthood. These data indicate that environmental exposures may cause adaptations to the germ cells that could provide the mechanistic basis for the cardiovascular dysfunction observed.

We found that these offspring had a variety of heart problems during the prime of their lives and the effects were so robust that it was somewhat shocking.

—senior author Loren Wold, director of biomedical research at Ohio State’s College of Nursing

Male and female mice were exposed to either filtered air (FA) or PM_2.5 at an average concentration of 38.58 µg/m³ for 6 hours/day, 5 days/week for 3 months. Mice were then crossbred into 2 groups: (1) FA_male x FA_female (both parents were exposed to FA preconception) and, (2) PM_2.5male x PM_2.5female (both parents were exposed to PM_2.5 preconception).

Male offspring were divided: (1) preconception FA (offspring born to FA exposed parents) and, (2) preconception PM_2.5 (offspring born to PM_2.5 exposed parents) and analyzed at 3 months of age.

In the PM_2.5 offspring, heart function was impaired. Inflammatory markers linked to increased heart disease risk were high. They had markers of oxidative stress, a condition in which levels of beneficial antioxidants are low. Calcium regulatory proteins, which are critical to the function of the beating heart, were altered. These mice were young and otherwise healthy—comparable to 20-year-old humans.

This suggests that heart problems related to pollution exposure could start even before conception, and if that’s true it has implications worldwide.

—Loren Wold

Wold and his team also uncovered evidence of gene-related differences that might explain the cardiovascular changes they saw. They examined epigenetic regulators, which play an important role in the expression of genes—meaning that they have influence over predisposition to health problems, including cardiovascular disease.

I looked at important epigenetic regulators in the offspring, and some were activated, which could explain the differences we saw. The next step will be a more-detailed analysis.

—study lead author Vineeta Tanwar, a research scientist at Ohio State

To conduct the study, researchers concentrated air from Columbus, Ohio, until the level of harmful particulate matter reached a level on par with large cities such as Los Angeles and Beijing.

The mice were kept in normal air during mating and the researchers compared their offspring to the offspring of mice that were not exposed to the polluted air.

The first thing we did was to do a basic echocardiograph and we could see profound heart dysfunction in the offspring of particulate-matter-exposed mice. Then, we began to look at single cells and at typical markers of heart disease and found a lot more evidence that preconception pollution could harm the offspring.

—Vineeta Tanwar

The study focused only on male offspring because the research team wanted to narrow its focus on this first experiment. Going forward, they plan to compare male and female offspring, to try to determine which parent’s exposure might matter more to offspring, to evaluate heart health later in the lifespan of the mice and to explore potential changes in the eggs and sperm of mice exposed to air pollution.

A key question here is how are changes in the sperm and eggs passing on the information to the offspring to cause this heart dysfunction.

—Loren Wold

Though more animal research is needed, this study also opens the door to exploring the role of air pollution on the health of future generations, Wold said. For example, it might make sense to begin by working with adults with high levels of exposure to particulate matter, such as residents of New Delhi and Beijing, Wold said.

The study was supported by the National Institutes of Health.

Resources

• Vineeta Tanwar, Jeremy M. Adelstein, Jacob A. Grimmer, Dane J. Youtz, Aashish Katapadi, Benjamin P. Sugar, Michael J. Falvo, Lisa A. Baer, Kristin I. Stanford, Loren E. Wold (2018) “Preconception Exposure to Fine Particulate Matter Leads to Cardiac Dysfunction in Adult Male Offspring” Journal of the American Heart Association doi: 10.1161/JAHA.118.010797. 2018;7:e010797