Happy worms have healthy eggs

Newswise —

Worms might not be depressed, per se. But that doesn’t mean they can’t benefit from antidepressants.

In a recent investigation, scientists from Northwestern University administered selective serotonin reuptake inhibitors (SSRIs), a type of medication utilized for managing depression and anxiety, to roundworms (a commonly used biological research model). To their astonishment, this intervention enhanced the caliber of egg cells in mature females.

The administration of SSRIs not only led to a reduction of over two times in embryonic mortality but also resulted in over a two-fold decline in chromosomal anomalies among the offspring that survived. Furthermore, upon microscopic examination, the egg cells appeared more youthful and robust, displaying a round and plump shape rather than a small and distorted one, which is frequently observed with age.

The scientists were amazed by the outcomes, and to validate their findings, they replicated the trial on fruit flies, which are also a widely used model organism. The SSRIs produced a similar impact in the fruit flies as well.

Despite the need for further research, the investigators suggest that these discoveries open up new prospects to investigate pharmacological treatments that could address infertility problems in humans. This could be achieved by enhancing egg quality and postponing the commencement of reproductive aging.

The publication of this research is scheduled for May 8 in the journal Developmental Biology. However, an initial draft of the manuscript is currently accessible here.

Ilya Ruvinsky, the leader of the study from Northwestern University, commented that "there is still a significant gap between this latest discovery and its potential application in fertility clinics." However, he added that as we continue to study the reproductive system, we will gain a better understanding of it, which could lead to the development of practical interventions.

Ilya Ruvinsky isan associate research professor at Northwestern University's Weinberg College of Arts and Sciences and the leader of this study. The paper's first author is Erin Aprison, a research associate in Ruvinsky's laboratory, while Svetlana Dzitoyeva, a postdoctoral researcher in Ruvinsky's laboratory, is a co-author of the paper.

Cutting out the middleman

In a previous study, Ruvinsky's research team found that male pheromones could delay the aging of female egg cells. This study was published in May 2022 in the Proceedings of the National Academy of Sciences. In this earlier investigation, the researchers exposed female roundworms to male pheromones, which led to the production of healthier offspring.

According to Ruvinsky, when female roundworms detected male pheromones, they redirected their energy and resources away from their general bodily health and toward enhancing their reproductive health. "The pheromone encourages the female to provide assistance to her eggs while neglecting the rest of her body," he explained. "It's not a complete shift; instead, it's a rebalancing."

In the new study, Ruvinsky and his team decided to remove male pheromones from the equation entirely.

Ruvinsky explained that the neurons responsible for signaling the body to redirect its resources utilize serotonin as the messenger. He added that his team had previously identified these neurons and speculated about whether it was feasible to directly engage with this system. They considered the possibility of stimulating the serotonin system using pharmaceuticals, thereby bypassing the necessity for male pheromones. To their surprise, they discovered that the direct administration of SSRIs resulted in enhanced egg quality by all measures.

Delaying decline

To carry out the investigation, the team incorporated a small dose of SSRIs into the food of aging roundworms. The study focused primarily on the effects of fluoxetine (Prozac), but the researchers also tested citalopram (Celexa) and zimelidine.

The researchers administered SSRIs continuously to the aging roundworms at concentrations similar to those used to treat depression and anxiety in humans. As worms age, their egg quality typically declines rapidly; however, those treated with fluoxetine were able to delay the onset of this decline.

Ruvinsky explained that when they administered the drug on a temporary basis and then discontinued it, the egg quality remained high for a brief period before quickly declining. The team believes this is due to the requirement for a continuous signal.

Ruvinsky and his colleagues also observed that fluoxetine exposure resulted in the production of a greater number of egg cell precursors in roundworms. Strangely enough, more of these cells died. However, this, too, was deemed to be beneficial.

Ruvinsky clarified, "To create higher-quality eggs, you need components from other eggs. This is achieved by using parts from other eggs that have died and gone to the 'salvage yard.' You break up the parts and use them to make the few eggs that survive higher quality."

Shared signaling

To determine whether the findings were specific to roundworms or generalizable to other organisms, Ruvinsky and his team repeated the experiment using fruit flies. Once again, exposure to fluoxetine resulted in improved egg quality in older female flies.

Although worms, flies and humans might seem very different, they have more in common than most people realize.

According to Ruvinsky, the serotonin system behaves similarly in various animals. Increasing serotonin levels in the brain prompts animals to prioritize food over exploring their environment, which is observed in mammals, flies, and worms alike. While it may not be possible to significantly expand the fertility window in humans, even a small extension of one or two years could have a significant impact.

The study, “Serotonergic signaling plays a deeply conserved role in improving oocyte quality,” was supported by the National Institutes of Health (award number R01GM126125).