Sex-specificity of the C. elegans metabolome
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Abstract
Recent studies of animal metabolism have revealed large numbers of novel metabolites that are involved in all aspects of organismal biology, but it is unclear to what extent metabolomes differ between sexes. Here, using untargeted comparative metabolomics for the analysis of wildtype animals and sex determination mutants, we show that C. elegans hermaphrodites and males exhibit pervasive metabolomic differences. Several hundred small molecules are produced exclusively or in much larger amounts in one sex, including a host of previously unreported metabolites that incorporate building blocks from nucleoside, carbohydrate, lipid, and amino acid metabolism. A subset of male-enriched metabolites is specifically associated with the presence of a male germline, whereas enrichment of other compounds requires a male soma. Further, we show that one of the male germline-dependent metabolites, an unusual dipeptide incorporating N , N -dimethyltryptophan, increases food consumption, reduces lifespan, and accelerates the last stage of larval development in hermaphrodites. Our results serve as a foundation for mechanistic studies of how the genetic sex of soma and germline shape the C. elegans metabolome and provide a blueprint for the discovery of sex-dependent metabolites in other animals.
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The metabolomic data from this study provide a resource for future detailed exploration of sex-biased metabolic pathways and phenotypes.
This elegant study provides a rich data set and a pathway to explore sex-specific metabolomic data in C. elegans and its involvement in a myriad of biological processes.
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Furthermore, chromatographic conditions optimized specifically for the detection of very polar and very non-polar metabolites (e.g. lipids) will almost certainly reveal additional male-upregulated compounds.
Given the large expansion of the nuclear hormone receptor (NHR) family in C. elegans, it will be very informative to explore lipid fractions for potential NHR ligands that likely regulate homeostasis, metabolism and reproduction.
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To this end, we examined the exo-metabolome of him-5 cultures by collecting the culture media during different time periods throughout larval development and adulthood (Figure 1c).
The decision to choose either male or hermaphroditic fate occurs very early in development, at around the 20 to 100 cell stage. It would be intriguing to examine if sex specific differences in metabolites is evident in the early embryonic stages of development, too. It may provide insights into how cell fate decisions are made and maintained.
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Furthermore, chromatographic conditions optimized specifically for the detection of very polar and very non-polar metabolites (e.g. lipids) will almost certainly reveal additional male-upregulated compounds.
Given the large expansion of the nuclear hormone receptor (NHR) family in C. elegans, it will be very informative to explore lipid fractions for potential NHR ligands that likely regulate homeostasis, metabolism and reproduction.
-
To this end, we examined the exo-metabolome of him-5 cultures by collecting the culture media during different time periods throughout larval development and adulthood (Figure 1c).
The decision to choose either male or hermaphroditic fate occurs very early in development, at around the 20 to 100 cell stage. It would be intriguing to examine if sex specific differences in metabolites is evident in the early embryonic stages of development, too. It may provide insights into how cell fate decisions are made and maintained.
-
The metabolomic data from this study provide a resource for future detailed exploration of sex-biased metabolic pathways and phenotypes.
This elegant study provides a rich data set and a pathway to explore sex-specific metabolomic data in C. elegans and its involvement in a myriad of biological processes.
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