April 22, 2016, BY Matt Hughes

Avoiding excess stress while pregnant seems like common sense, but according to Bucknell University Professor Mark Haussmann, there's mounting medical evidence to back up that notion. Stress during pregnancy, he said, has been linked to offspring having difficulty dealing with stress later in life, as well as higher susceptibility to disease and even shorter lifespans.

Haussmann, biology, has received a $330,000 grant from the National Institutes of Health to conduct a three-year study of the connection between prenatal stress and premature aging, using quail as a model. Haussmann's research examines how stressed mothers can pass "stress hormones," specifically the hormone corticosterone, to their children in the womb.

"There is evidence from my lab and others that if you experience high levels of these hormones in the womb, it can cause you to age prematurely," he explained.

"This is problematic because as the embryo's own physiological system for coping with stress is being set up, it's being bombarded with stress hormones from mom," he continued. "That results in a system that thinks that a high level of stress is normal. So later in life, when these individuals get into stressful situations, their stress systems overreact and release high levels of stress hormones. We're looking at how that has a cumulative affect on aging."

Hannah Litwa '18 prepares to inject a quail egg as Professor Mark Haussmann observes. Photo by Brett Simpson, Division of Communications

The grant will allow Haussmann to examine how prenatal stress hormones affect stress responses and aging in birds exposed to high corticosterone as embryos. It will also support a postdoctoral researcher (Ryan Paitz of Illinois State University) and 18 summer research stipends for Bucknell students, six per year over the next three years.

One of the students who will benefit from such a stipend is Hannah Litwa '18, who has been studying the impact of corticosterone alongside Haussmann since last summer.

"Working in Mark's lab has been an incredibly productive and insightful experience," Litwa said. "While I have gotten a lot of experience learning lab techniques, it has also provided me the opportunity to see what a career in research and academia has to offer.

"One of the most exciting aspects of working with Mark is that even I am unsure of how much I can accomplish — it seems like the possibilities are endless."

The grant follows a 2012 study in which Haussmann found that chicken eggs injected with corticosterone were genetically pre-programmed toward overactive stress responses later in life, and were likely to have shorter lifespans.

"It was the first experimental study showing that experiencing high levels of these stress hormones during fetal development could result in a faster rate of cellular aging," Haussmann said. "That study only lasted a few weeks, but we hypothesized that if we had followed individuals until they were adults, we would have seen higher disease incidence and earlier mortality in the prenatally stressed birds."

The upcoming study will follow birds, in this case Japanese quail, throughout their lives (about three years on average), allowing Haussmann and his students to observe the impact of prenatal stress hormones over the entire lifespan, another scientific first.

"The first- and second-year students in my lab will be able to observe these birds the whole time they're at Bucknell," he added.

The Japanese quail in Haussmann's lab may reveal connections between prenatal stress and premature aging, even in humans. Photo by Brett Simpson, Division of Communications

The study will also examine how developing offspring might be able to cope with and defend themselves against maternal stress hormones, using a concept called the embryonic buffer.

"While stress hormones can impact the developing embryo, it's not totally defenseless," Haussmann said. "There is an embryonic buffer that can deactivate stress hormones, but problems can arise when the mother's stress hormones overwhelm this buffer. It's like a game of Red Rover — once the stress hormones break through, they have adverse effects."

While Haussmann can't say with certainty whether the results of the study will hold true for people as well as birds, he said the "stress system" of humans and Japanese quail is "amazingly similar, and so are their cellular aging mechanisms."

Gianna Tricola '18 (left) and Melanie Grossman '17 transfer a gel containing DNA telomeres to a chemical bath in Haussmann's lab. Photo by Brett Simpson, Division of Communications

Another study in which Haussmann and Bucknell students participated — which was published in February in the American Journal of Obstetrics and Gynecology — also suggests a correlation between prenatal stress and a genetic predisposition toward shorter lives in humans. In that study, expecting mothers were surveyed about situations that caused stress during their pregnancy (such as job loss, the death of a family member or divorce) and were assigned a stress score based on their responses.

After the mothers gave birth, doctors at Drexel University in Philadelphia collected blood samples from the umbilical cords for analysis in Haussmann's lab. Haussmann and his partners found shorter telomeres — protective caps on the ends of DNA strands, which correlate with shorter lifespans — in the children of mothers who experienced more stress during pregnancy.

"While we can't say that those kids will have higher rates of disease or shorter lifespans, that's what current data in the field indicates," he said.

Haussmann's research provides as good a reason as any, it seems, for expecting mothers to take it easy as much as possible.