[
International Worm Meeting,
2021]
Social signals, including sex pheromones, play important roles in the decision-making of animals. These decisions range from short-term behavioral choices to binary, costly commitments. For example, our recent work established that C. elegans hermaphrodites select germline investment allocation strategies based on external stimuli, including food abundance and the presence of potential mating partners, signaled by the male ascaroside pheromone, ascr#10. This decision can only be made during a window of several hours in early adulthood. We seek to understand how this pheromone is sensed and integrated with other inputs by the nervous system, and its impact on hermaphrodite physiology. We used transcriptomics as an unbiased way to test several hypotheses regarding ascr#10 effects on hermaphrodites. First, prior work suggested that pre-reproductive adult hermaphrodites do not respond to this male pheromone. Instead, we found that these young adults show a substantial transcriptional signature that resembles the one seen in pheromone-responsive adults. We interpret this result as an indication that the lack of overt behavioral and physiological responses in younger worms may be due to targeted response modulation, not the complete absence of relevant receptor(s) or signal transduction components. Second, a specific serotonergic circuit, that is engaged upon the onset of egg laying, licenses behavioral and physiological responses to ascr#10. Transcriptomic responses to the pheromone in mutants that disrupt activity of this circuit identified ways in which serotonin modulates hermaphrodites responses to the presence of males and couples physiology to reproductive status. Finally, a comprehensive analysis of genes differentially expressed in response to ascr#10, revealed several physiological processes, and their regulators, that are likely responsible for the beneficial effects of this male pheromone on the hermaphrodite germline and the detrimental effects on organismal longevity.
[
International Worm Meeting,
2021]
Conspecific males and females communicate with potential mating partners via sex pheromones to promote reproductive success, but the underlying mechanisms remain largely enigmatic. We discovered how a C. elegans male pheromone, ascr#10, improves the oogenic germline and in the process identified an apparently conserved strategy to improve oocyte quality using commonly available pharmaceuticals. As they age, C. elegans hermaphrodites start producing lower quality oocytes characterized by abnormal morphology, increased rates of chromosomal nondisjunction, and higher penetrance of deleterious alleles. We showed that exposure to the male pheromone substantially ameliorates all of these defects and reduces embryonic lethality. ascr#10 stimulates proliferation of germline precursor cells in adult hermaphrodites. Greater precursor supply increases physiological germline cell death, which is required to improve oocyte quality in older mothers. Because ascr#10 effects on the germline require serotonergic signaling, we tested whether pharmaceuticals, including serotonin reuptake inhibitors, could improve germline quality in the absence of the pheromone. We found that compounds that potentiate serotonin signaling do indeed improve oocyte quality in C. elegans as well as in Drosophila. Together, our results suggest the male pheromone improves oocyte quality, but shortens organismal longevity because of the competition over resource allocation between soma and the germline. Practically, our findings reveal a class of therapeutic interventions using available compounds that could forestall reproductive aging.