A new study by Stanford University researchers has found that male roundworms are capable of secreting signaling molecules that seriously impacts the lifespan of their female counterparts. In contemplating the function of such signaling molecules, the group suggests that male roundworms trigger the premature demise of their female partners, in a bid to conserve precious resources for their progeny; this mariticidal practice is also thought to be responsible for pushing down the size of the female population, so that rival male worms are limited to fewer mates.
The capacity to lessen the lifespan of a species’ female equivalents has been previously observed in certain species of flies and worms; for example, male fruit flies release seminal fluids that contain toxins, which eventually prove fatal to female flies.
The exact mechanism of this process has remained elusive in several species. Some researchers posited that copulation introduced physical stress that led to their early death, but these theories were unsubstantiated.
Researchers from the Stanford University School of Medicine believed there was more to the issue, however, speculating that this apparent “male-induced demise” was a coordinated effort, enacted at a molecular level.
During the study, the results of which were published in the Nov. 28 issue of Science Express, researchers performed a series of laboratory investigations into the common roundworm, known as Caenorhabditis elegans (C. elegans). The worms are transparent nematodes, approximately one millimeter in length and frequently inhabit the soils of temperate climates.
The Nature of the Nematode
Anatomically speaking, the worms possess a mouth, intestine, pharynx and gonad. Male roundworms possess a vas deferens, gonad and tail, exercised for mating purposes, whilst hermaphrodites have a uterus, oviducts, ovaries and a sperm-storing organ called a receptaculum seminis.
All in all, the worms have an average life expectancy of approximately 20 days. Just 0.01 to 0.1 percent of the population comprises of male roundworms, with the remainder consisting of hermaphrodites. The hermaphrodites have male and female reproductive organs and are able to self-fertilize. However, regular fertilization with a male partner is preferred, since it results in a much greater number of offspring.
Based upon the evidence collected during the group’s many experiments, Associate Professor of Genetics Anne Brunet, PhD, explains that male roundworms expressed a vast number of genes that influenced “sensation and signaling” in hermaphrodites. Merely placing the hermaphrodites on a plate that male worms had previously occupied was sufficient to induce their premature demise. Brunet consolidates these findings, with those hypotheses submitted by other researchers:
“This raises the possibility that the male-induced demise is not just due to the physical stress of copulation but instead involves some degree of active signaling.”
Brunet discusses the evolutionary requirement for this facility, suggesting that females are an expendable drain on scarce resources, including food. Once the male has mated, and the eggs have been produced, the hermaphrodite mother can be killed. This brutal act also prevents other male roundworms from mating with her, thereby reducing the chances of competing males from reproducing and introducing their genes into the gene pool.
Killer Molecular Signals Trigger Hermaphrodite Aging
In studying the affect of male and female co-mingling, they found that young nematode males were responsible for reducing the lifespan of hermaphrodite worms by over 20 percent. This reduction remained evident when the different genders were separated and when C. elegans hermaphrodites were sterilized. Based upon these findings, the authors tentatively suggest that neither physical stresses, encountered during the act of mating, nor the energy required for reproduction could solely explain the reduced lifespan of females.
In addition, after the “killer molecular signals” were deployed, hermaphrodite worms were afflicted with a number of ailments, including impaired movement and increased risk of paralysis, and were also struck by general decrepitude, structural abnormalities and degeneration of internal organs.
Ultimately, the hermaphrodites were destined to undergo an accelerated aging process and, as a consequence, rapidly displayed many of the characteristic symptoms of aging. Even stress-resistant C. elegans hermaphrodites were adversely affected by the signals.
The team’s research demonstrated that males were capable of commencing the killing process across large distances. After placing hermaphrodites onto laboratory plates that had previously been home to male worms, the attendant reduction in lifespan led researchers to speculate that the males were leaving behind a specific substance that was responsible for inducing premature death.
However, this affect was neutered by preventing the male worms from secreting pheromones, as discussed by Brunet during a recent press release:
“Males that are deficient in pheromone production no longer induce a strong premature demise of hermaphrodites, and hermaphrodites that cannot sense pheromones are resistant to male-induced demise.”
Could Pheromones Prove to be the Killer Chemicals?
Pheromones are chemical messages typically released to generate a social or behavioral response from members of the same species. Whereas some pheromone chemicals act as “alarms,” warning fellow individuals of potential danger, others can serve as sex pheromones, using in attracting individuals of the opposite sex.
The team are yet to establish the means by which the pheromones are secreted, or the exact time this process takes place. However, they did determine the impact of the unidentified pheromones on the profiles of the hermaphrodite worms’ genetic expression. Specifically, large changes in expression were detected, only when male worms were nearby.
A number of alterations took place in genes expressed in neurons and neurodegenerative diseases, many of which were likely a part of the overall aging process, provoked by male pheromone release. The Stanford researchers then blocked the expression of the insulin-like peptide (ILP) INS-11 and, quite remarkably, found that it circumvented male-induced death in hermaphrodite test subjects.
Throughout the study, Brunet and colleagues confess, an unnaturally high number of C. elegans worms were used. However, the group feel that the affects of male pheromones are likely to be exaggerated when mating under real-world conditions; this affect could be even more pronounced if the pheromones are combined with released seminal fluid.
But how would these fluids end up on the laboratory plates, even in the absence of females? It has been suggested that the males were attempting to unsuccessfully mate with one another and, hence released the seminal fluid for this reason.
Applicability to Other Species
This then raises another interesting question; could similar pheromones be responsible for triggering the same affects in other species, including different species of mammal?
This is something that the group has not yet tested. However, they managed to confirm that the pheromone triggered male-induced death in distantly related species of worms; the group claims this finding demonstrates the phenomenon to have been conserved over a time period of 20 to 30 million years.
So, although the group have discovered that pheromone signaling of C. elegans worms shortens the lifespan of hermaphrodites, Brunet conjectures this could perhaps extend to a number of other species:
“It will be interesting, of course, to determine whether males also affect the lifespan of females in other species, particularly mammals.”
Sean Curran, a biogerontologist at the University of Southern California in Los Angeles, suggests that this latest research will remain a “hot topic” of debate, within the scientific community, for some time to come. In wrapping up, he explains that attempting to figure out whether the same process occurs in long-living mammals will be a far more complicated process.
By James Fenner