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[
International Worm Meeting,
2013]
Organisms have to protect their reproductive capacity from harsh environmental extremes. We tracked changes in the C. elegans reproductive system during chronic heat stress to uncover the strategies used by worms to deal with high temperatures of unknown duration. C. elegans can recover from prolonged heat stress and resume laying eggs. The likelihood of producing viable offspring after recovery falls precipitously after exposure to temperatures greater than 28 deg C but takes a curious upturn at 31 deg C, and then continues to fall at higher temperatures. We show that most of the loss of fecundity at high temperature is due to sperm damage. We can explain the spike in the likelihood of producing viable progeny after exposure to 31 deg C because at that temperature worms do not begin to ovulate. Absent ovulation, which is necessary for spermatid activation, all spermatids remain as spermatids, a cell type that appears to be more heat tolerant than mature sperm. In addition, failure to ovulate mitigates damage to the reproductive system. Consistent with this idea, we show that mutants that continue to ovulate at high temperature are less likely to recover progeny, while chemical treatments suppressing ovulation increase the likelihood of recovering progeny. We interpret these dynamic responses as an adaptation to life in variable and unpredictable conditions. The reproductive system of C. elegans is exquisitely tuned, such that when temperatures rise above those consistent with larval viability, worms stop ovulating and shut down the reproductive system. This provides a fail-safe response that protects the system from damage by heat stress and preserves its capacity for a time when conditions improve. We show, however, that there is a cost associated with this strategy - it takes considerable time to recover and produce offspring. At temperatures approaching the fail-safe temperature, worms must make a decision to continue reproducing or shut down. Our results suggest that depending on the duration of heat stress either strategy may be advantageous. Heterogeneity that we observed in response to harsher conditions may be a form of bet hedging to ensure the continuation of the population in fluctuating environments.
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[
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.
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[
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.
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Aprison, Erin Z., Amaral, Luis A., Ruvinsky, Ilya, Morimoto, Richard I., McMullen, Patrick D., Winter, Peter
[
International Worm Meeting,
2011]
A major goal of systems biology is to understand how complex emergent properties of organisms arise from interactions of individual components. We developed an analytical model of the reproductive system of C. elegans using basic engineering principles. Although the model incorporated only a few of the many known features of nematode reproduction, it provided quantitatively accurate predictions of performance under a variety of chronic heat stress conditions, as verified by detailed time-resolved experimental data. This suggests that dynamic systems behaviors may be determined by only a small number of key components. Our approach is general and can be applied to other biological systems to reveal which processes within organisms give rise to their dynamic behavior. Importantly, we found that whereas under ambient conditions brood size distribution for individual worms was unimodal (indeed normal), under conditions of harsh stress, when the reproductive system was near shutdown, it was best described by a combination of a normal and an exponential distribution. This implies the existence of a hidden heterogeneity in a population - some animals continue to act robustly, while others display loss of control over performance variance. This hints at the existence of a general principle that governs behavior of robust systems as they near complete collapse.