Zebrafish help Kentucky researchers advance understanding of fetal alcohol syndrome
Republished from Kentucky Lantern
LOUISVILLE — Over the next five years, University of Louisville researchers plan to expose about 1.5 million fish eggs to alcohol in hopes of better understanding fetal alcohol syndrome in humans.
Using a $2.3 million grant from the National Institutes of Health, researchers will study zebrafish as a model for better understanding human facial defects associated with prenatal exposure to alcohol. They started their work in May and will finish in 2029.
Ben Lovely, the study’s lead researcher and an assistant professor of biochemistry and molecular genetics at the university, said zebrafish are “a really strong model for humans” because they share more than 80% of the same genes.
“If you have a gene that’s associated with cancer in humans, you’re probably going to find it in fish, and it can lead to cancer in a fish,” Lovely explained.
Because of this, he told the Lantern, he can study the effects of alcohol on humans via the fish, learning more than he would be able to in a human study. Fish are well equipped for such a study, he said — he can study developing embryos outside the mother.
“Part of the issue with looking at placental mammals like humans, like mice, is maternal effects and embryonic effects,” he said. “So you have two different things going on here.”
With his zebrafish, which are raised in a facility on-site and “get fed and mate” for a living, he can take eggs that adult fish laid and study them in petri dishes — about 100 at a time to ensure they don’t die from over-density. Zebrafish are a freshwater member of the minnow family.
During their time in the dish, researchers control how much alcohol is added to the solution in each dish, which also has water and nutrients.
“The alcohol goes right into the fish, gets right across the eggshell and into the fish itself,” he explained. The alcohol dose isn’t enough to kill the fish, he said.
These fish are also perfect for monitoring early development.
“They develop pigments once they reach adult stages, but as embryos, they’re transparent,” Lovely said. “You can see right through them. So we can actually watch the cells live in a developing fish over time. You can’t really do that in a placental mammal, because you’d have to remove the embryo to get that to happen.”
Decreasing stigma
Babies who were exposed to alcohol while in utero — especially in the early weeks when a person may not know they are pregnant — can be born with fetal alcohol spectrum disorders (FASDs), which includes the incurable fetal alcohol syndrome.
People born with this may have “abnormal facial features” like a smooth ridge between the nose and upper lip, a thin upper lip and small eyes, according to the Cleveland Clinic. Other symptoms can include learning problems, attention deficit hyperactivity disorder (ADHD), depression and more.
Both the alcohol consumption and the facial features he is specifically studying can lead to stigma, Lovely said.
“The first thing we see as humans is the face. So facial birth defects are hugely stigmatizing,” he said. “To understand their origins, their prognosis, everything about them is going to be key in really helping identify these issues early, if we can, especially prenatally, that would be more ideal.”
Alcohol, too, “has its own stigma,” he said.
The Centers for Disease Control and Prevention reported in 2019 that about 42% of pregnancies in the United States are unintended. The early weeks and months of pregnancy are a key time for the developments of FASD, according to the Mayo Clinic.
“So you combine those two: there are a lot of individuals who are drinking and do not know they’re pregnant,” Lovely said. “They don’t want to be accused of harming their child because they didn’t know, right? That’s the stigma. So it’s very difficult for him to do human studies. It’s very difficult to find patients — very few mothers want to admit to this.”
But through his zebrafish study, he said, he hopes to move in the direction of genotyping a person to see their sensitivity to alcohol and look at the issue more from a gene perspective and less from a social perspective.
“A lot of researchers now … say ‘prenatal exposure,’ we don’t say ‘the mother drank,’” he said. “We don’t say anything about the mother, to avoid stigmatizing the mother. So we try to couch it from ‘this has happened to the developing embryo,’ not ‘this was done to the developing embryo.’”
The CDC said this year that about 1 in 20 school-aged children in the country could have FASDs. Not every fetus that’s exposed to alcohol will develop FASD issues.
Because of this, the University of Louisville says that “understanding what genes might increase that risk could lead to better therapeutics and help mothers make safer, more informed choices.”
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