Northwestern University researchers have conducted a study where roundworms were exposed to selective serotonin reuptake inhibitors (SSRIs), a type of drug typically used to treat depression and anxiety. The researchers were surprised to find that this treatment actually improved the quality of aging female worms’ egg cells.
The researchers discovered that the SSRIs decreased embryonic death by over two times, while also reducing chromosomal abnormalities in surviving offspring by over two times. The egg cells of the worms looked younger and healthier, appearing round and plump rather than misshapen, which is a common issue with aging.
After replicating the experiment in fruit flies, the researchers were astonished to find that the SSRIs had the same effect.
While there is still more work to be done, the researchers believe that these findings present new opportunities to explore how pharmacological interventions could improve egg quality and delay the onset of reproductive aging, potentially leading to treatments for infertility issues in humans.
The study was published in the journal Developmental Biology. Ilya Ruvinsky, an associate research professor at Northwestern’s Weinberg College of Arts and Sciences, led the study. Research associate Erin Aprison was the paper’s first author, and postdoctoral researcher Svetlana Dzitoyeva co-authored the paper.
Ruvinsky notes that there is still a long way to go before these findings can be used in fertility clinics, but the more that is learned about the reproductive system, the greater the potential for practical interventions.
Cutting out the middleman
In a previous study published in May 2022 in Proceedings of the National Academy of Sciences, Ruvinsky’s team discovered that male pheromones could slow the aging of female roundworms’ egg cells. The study found that exposure to male pheromones resulted in healthier offspring, as the female roundworms shifted their energy and resources away from their overall body health and towards increasing their reproductive health.
For their latest study, Ruvinsky’s team wanted to remove male pheromones from the equation and see if they could stimulate the serotonin system directly. The researchers identified the neurons that signal the body to shift its resources in their previous work and wondered if they could bypass the need for male pheromones by stimulating the serotonin system with pharmaceuticals. The study found that by doing so, the quality of aging female roundworms’ egg cells improved significantly, resulting in healthier offspring by every measure.
For the study, the researchers added a low dose of SSRIs to the food of aging roundworms and explored the effects of fluoxetine, citalopram, and zimelidine. The team exposed the roundworms continuously to the SSRIs at concentrations comparable to those used to treat anxiety and depression in humans.
The study found that worms treated with fluoxetine managed to stave off the decline in egg quality that typically occurs as they age. However, when the researchers delivered a temporary regimen of the drug and then withdrew it, the egg quality stayed high for a while but quickly decreased. The team believes that the roundworms need a continuous signal.
Additionally, exposure to fluoxetine led to the production of more egg cell precursors, but more of these cells died. This seemingly counterproductive effect is advantageous because it provides the components to make higher-quality eggs. Ruvinsky explained that many eggs die and get sent to the “salvage yard,” where the parts get broken up and used for the few eggs that survive.
The team led by Ruvinsky wanted to determine whether the findings they obtained with worms also applied to other animals. Thus, they replicated the study using fruit flies and, once again, found that fluoxetine improved the quality of older female flies’ eggs.
Despite their apparent differences, worms, flies, and humans have more similarities than we might think.
“The same neuronal system works similarly in different animals,” Ruvinsky said. “When animals have more serotonin in their brains, they focus on food rather than exploring their surroundings. This is true for mammals, flies, and worms. While it may not be possible to extend the fertility window to 60 years, if we could add a year or two to someone’s fertility window, it would make a significant difference.”