Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Perceptive costs of reproduction drive ageing and physiology in male Drosophila

Nature Ecology & Evolution volume 1, Article number: 0152 (2017) Cite this article

Subjects

Abstract

Costs of reproduction are thought to result from natural selection optimizing organismal fitness within putative physiological constraints. Phenotypic and population genetic studies of reproductive costs are plentiful across taxa, but an understanding of their mechanistic basis would provide important insight into the diversity in life-history traits, including reproductive effort and ageing. Here, we dissect the causes and consequences of specific costs of reproduction in male Drosophila melanogaster. We find that key survival and physiological costs of reproduction arise from perception of the opposite sex, and they are reversed by the act of mating. In the absence of pheromone perception, males are free from reproductive costs on longevity, stress resistance and fat storage. The costs of perception and the benefits of mating are both mediated by evolutionarily conserved neuropeptidergic signalling molecules, as well as the transcription factor dFoxo. These results provide a molecular framework in which certain costs of reproduction arise as a result of self-imposed ‘decisions’ in response to perceptive neural circuits, which then orchestrate the control of life-history traits independently of physical or energetic effects associated with mating itself.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Pheromone exposure, and not mating, drives the physiological costs of reproduction.
Figure 2: Pheromone exposure and mating drive separate global changes in the neurometabolome.
Figure 3: Self-imposed costs of reproduction are mediated by specific peptidergic neurons.
Figure 4: Self-imposed costs of reproduction are mediated through dFoxo signalling by a dILP2/3/5-independent mechanism.

Similar content being viewed by others

References

  1. Reznick, D. Measuring the costs of reproduction. Trends Ecol. Evol. 7, 42–45 (1992).

    Article  Google Scholar 

  2. Browne, R. A. The costs of reproduction in brine shrimp. Ecology 63, 43–47 (1982).

    Article  Google Scholar 

  3. Van Voorhies, W. A. Production of sperm reduces nematode lifespan. Nature 360, 456–458 (1992).

    Article  CAS  Google Scholar 

  4. Maynard Smith, J. The effects of temperature and of egg-laying on the longevity of Drosophila subobscura. J. Exp. Biol. 35, 832–842 (1958).

    Google Scholar 

  5. Koivula, M., Koskela, E., Mappes, T. & Oksanen, T. A. Cost of reproduction in the wild: manipulation of reproductive effort in the bank vole. Ecology 84, 398–405 (2003).

    Article  Google Scholar 

  6. Hoffman, C. L. et al. Sex differences in survival costs of reproduction in a promiscuous primate. Behav. Ecol. Sociobiol. 62, 1711–1718 (2008).

    Article  Google Scholar 

  7. Dallerac, R. et al. A Δ9 desaturase gene with a different substrate specificity is responsible for the cuticular diene hydrocarbon polymorphism in Drosophila melanogaster. Proc. Natl Acad. Sci. USA 97, 9449–9454 (2000).

    Article  CAS  Google Scholar 

  8. Min, K. J., Lee, C. K. & Park, H. N. The lifespan of Korean eunuchs. Curr. Biol. 22, R792–R793 (2012).

    Article  CAS  Google Scholar 

  9. Stearns, S. C. The Evolution of Life Histories (Oxford Univ. Press, 1992).

    Google Scholar 

  10. Speakman, J. R. The physiological costs of reproduction in small mammals. Phil. Trans. R. Soc. B 363, 375–398 (2008).

    Article  Google Scholar 

  11. Harshman, L. G. & Zera, A. J. The cost of reproduction: the devil in the details. Trends Ecol. Evol. 22, 80–86 (2007).

    Article  Google Scholar 

  12. Flatt, T. Survival costs of reproduction in Drosophila. Exp. Gerontol. 46, 369–375 (2011).

    Article  Google Scholar 

  13. Salmon, A. B., Marx, D. B. & Harshman, L. G. A cost of reproduction in Drosophila melanogaster: stress susceptibility. Evolution 55, 1600–1608 (2001).

    Article  CAS  Google Scholar 

  14. Chapman, T., Hutchings, J. & Partridge, L. No reduction in the cost of mating for Drosophila melanogaster females mating with spermless males. Proc. R. Soc. B 253, 211–217 (1993).

    Article  CAS  Google Scholar 

  15. Zajitschek, F., Zajitschek, S. R., Friberg, U. & Maklakov, A. A. Interactive effects of sex, social environment, dietary restriction, and methionine on survival and reproduction in fruit flies. Age 35, 1193–1204 (2013).

    Article  CAS  Google Scholar 

  16. Wigby, S. & Chapman, T. Sex peptide causes mating costs in female Drosophila melanogaster. Curr. Biol. 15, 316–321 (2005).

    Article  CAS  Google Scholar 

  17. Cordts, R. & Partridge, L. Courtship reduces longevity of male Drosophila melanogaster. Anim. Behav. 52, 269–278 (1996).

    Article  Google Scholar 

  18. O’Brien, D. M., Min, K. J., Larsen, T. & Tatar, M. Use of stable isotopes to examine how dietary restriction extends Drosophila lifespan. Curr. Biol. 18, R155–R156 (2008).

    Article  Google Scholar 

  19. Djawdan, M., Sugiyama, T. T., Schlaeger, L. K., Bradley, T. J. & Rose, M. R. Metabolic aspects of the trade-off between fecundity and longevity in Drosophila melanogaster. Physiol. Zool. 69, 1176–1195 (1996).

    Article  Google Scholar 

  20. Barnes, A. I., Wigby, S., Boone, J. M., Partridge, L. & Chapman, T. Feeding, fecundity and lifespan in female Drosophila melanogaster. Proc. R. Soc. B 275, 1675–1683 (2008).

    Article  Google Scholar 

  21. Sujkowski, A., Bazzell, B., Carpenter, K., Arking, R. & Wessells, R. J. Endurance exercise and selective breeding for longevity extend Drosophila healthspan by overlapping mechanisms. Aging 7, 535–552 (2015).

    Article  CAS  Google Scholar 

  22. Maures, T. J. et al. Males shorten the life span of C. elegans hermaphrodites via secreted compounds. Science 343, 541–544 (2014).

    Article  CAS  Google Scholar 

  23. Gendron, C. M. et al. Drosophila life span and physiology are modulated by sexual perception and reward. Science 343, 544–548 (2014).

    Article  CAS  Google Scholar 

  24. Shi, C. & Murphy, C. T. Mating induces shrinking and death in Caenorhabditis mothers. Science 343, 536–540 (2014).

    Article  CAS  Google Scholar 

  25. Thistle, R., Cameron, P., Ghorayshi, A., Dennison, L. & Scott, K. Contact chemoreceptors mediate male–male repulsion and male–female attraction during Drosophila courtship. Cell 149, 1140–1151 (2012).

    Article  CAS  Google Scholar 

  26. Shohat-Ophir, G., Kaun, K. R., Azanchi, R. & Heberlein, U. Sexual deprivation increases ethanol intake in Drosophila. Science 335, 1351–1355 (2012).

    Article  CAS  Google Scholar 

  27. Wu, Q., Zhao, Z. & Shen, P. Regulation of aversion to noxious food by Drosophila neuropeptide Y- and insulin-like systems. Nat. Neurosci. 8, 1350–1355 (2005).

    Article  CAS  Google Scholar 

  28. Junger, M. A. et al. The Drosophila Forkhead transcription factor FOXO mediates the reduction in cell number associated with reduced insulin signaling. J. Biol. 2, 20 (2003).

    Article  Google Scholar 

  29. Rera, M., Clark, R. I. & Walker, D. W. Intestinal barrier dysfunction links metabolic and inflammatory markers of aging to death in Drosophila. Proc. Natl Acad. Sci. USA 109, 21528–21533 (2012).

    Article  CAS  Google Scholar 

  30. Landis, G., Shen, J. & Tower, J. Gene expression changes in response to aging compared to heat stress, oxidative stress and ionizing radiation in Drosophila melanogaster. Aging 4, 768–789 (2012).

    Article  CAS  Google Scholar 

  31. Slack, C., Giannakou, M. E., Foley, A., Goss, M. & Partridge, L. dFOXO-independent effects of reduced insulin-like signaling in Drosophila. Aging Cell 10, 735–748 (2011).

    Article  CAS  Google Scholar 

  32. Weber, K., Johnson, N., Champlin, D. & Patty, A. Many P-element insertions affect wing shape in Drosophila melanogaster. Genetics 169, 1461–1475 (2005).

    Article  CAS  Google Scholar 

  33. Broughton, S. J. et al. DILP-producing median neurosecretory cells in the Drosophila brain mediate the response of lifespan to nutrition. Aging Cell 9, 336–346 (2010).

    Article  CAS  Google Scholar 

  34. Gronke, S., Clarke, D. F., Broughton, S., Andrews, T. D. & Partridge, L. Molecular evolution and functional characterization of Drosophila insulin-like peptides. PLoS Genet. 6, e1000857 (2010).

    Article  Google Scholar 

  35. Hwangbo, D. S., Gershman, B., Tu, M. P., Palmer, M. & Tatar, M. Drosophila dFOXO controls lifespan and regulates insulin signalling in brain and fat body. Nature 429, 562–566 (2004).

    Article  CAS  Google Scholar 

  36. Lu, B., LaMora, A., Sun, Y., Welsh, M. J. & Ben-Shahar, Y. ppk23-dependent chemosensory functions contribute to courtship behavior in Drosophila melanogaster. PLoS Genet. 8, e1002587 (2012).

    Article  CAS  Google Scholar 

  37. Wen, T., Parrish, C. A., Xu, D., Wu, Q. & Shen, P. Drosophila neuropeptide F and its receptor, NPFR1, define a signaling pathway that acutely modulates alcohol sensitivity. Proc. Natl Acad. Sci. USA 102, 2141–2146 (2005).

    Article  CAS  Google Scholar 

  38. Fowler, K. & Partridge, L. A cost of mating in female fruitflies. Nature 338, 760–761 (1989).

    Article  Google Scholar 

  39. Soma, K. K., Francis, R. C., Wingfield, J. C. & Fernald, R. D. Androgen regulation of hypothalamic neurons containing gonadotropin-releasing hormone in a cichlid fish: integration with social cues. Horm. Behav. 30, 216–226 (1996).

    Article  CAS  Google Scholar 

  40. Zhang, G. et al. Hypothalamic programming of systemic ageing involving IKK-β, NF-κB and GnRH. Nature 497, 211–216 (2013).

    Article  CAS  Google Scholar 

  41. Gaikwad, A., Biju, K. C., Muthal, P. L., Saha, S. & Subhedar, N. Role of neuropeptide Y in the regulation of gonadotropin releasing hormone system in the forebrain of Clarias batrachus (Linn.): immunocytochemistry and high performance liquid chromatography-electrospray ionization-mass spectrometric analysis. Neuroscience 133, 267–279 (2005).

    Article  CAS  Google Scholar 

  42. Turi, G. F., Liposits, Z., Moenter, S. M., Fekete, C. & Hrabovszky, E. Origin of neuropeptide Y-containing afferents to gonadotropin-releasing hormone neurons in male mice. Endocrinology 144, 4967–4974 (2003).

    Article  CAS  Google Scholar 

  43. Anderson, D. J. & Adolphs, R. A framework for studying emotions across species. Cell 157, 187–200 (2014).

    Article  CAS  Google Scholar 

  44. Kato, K., Zweig, R., Schechter, C. B., Barzilai, N. & Atzmon, G. Positive attitude toward life, emotional expression, self-rated health, and depressive symptoms among centenarians and near-centenarians. Aging Ment. Health 20, 930–939 (2016).

    Article  Google Scholar 

  45. Lindau, S. T. et al. A study of sexuality and health among older adults in the United States. N. Engl. J. Med. 357, 762–774 (2007).

    Article  CAS  Google Scholar 

  46. Brody, S. Blood pressure reactivity to stress is better for people who recently had penile-vaginal intercourse than for people who had other or no sexual activity. Biol. Psychol. 71, 214–222 (2006).

    Article  Google Scholar 

  47. Lewis, E. A new standard food medium. Dros. Info. Service 34, 117–118 (1960).

    Google Scholar 

  48. Kondo, S. & Ueda, R. Highly improved gene targeting by germline-specific Cas9 expression in Drosophila. Genetics 195, 715–721 (2013).

    Article  CAS  Google Scholar 

  49. Linford, N. J., Bilgir, C., Ro, J. & Pletcher, S. D. Measurement of lifespan in Drosophila melanogaster. J. Vis. Exp. 71, e50068 (2013).

    Google Scholar 

  50. Pasco, M. Y . & Leopold, P. High sugar-induced insulin resistance in Drosophila relies on the lipocalin Neural Lazarillo. PLoS ONE 7, e36583 (2012).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Members of the Pletcher laboratory provided comments on the experimental design and analysis. This research was supported by the US National Institutes of Health (R01AG030593 and R01AG051649 to S.D.P., R01AG049494 to D.E.L.P., and R01GM102279 to S.D.P and D.E.L.P.), the Glenn Medical Foundation (to S.D.P.), a Ruth L. Kirschstein National Research Service Award from NIA (F30AG048661, to Z.M.H.) and the University of Michigan Systems Biology Training Grant (T32GM008322, to Z.M.H.).

Author information

Authors and Affiliations

  1. Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, 48109, Michigan, USA.

    Zachary M. Harvanek, Yang Lyu, Christi M. Gendron, Jacob C. Johnson & Scott D. Pletcher

  2. Medical Scientist Training Program, University of Michigan, Ann Arbor, 48109, Michigan, USA.

    Zachary M. Harvanek

  3. Genetic Strains Research Center, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan.

    Shu Kondo

  4. Department of Pathology, University of Washington, Seattle, 98195, Washington, USA.

    Daniel E. L. Promislow

  5. Department of Biology, University of Washington, Seattle, 98195, Washington, USA.

    Daniel E. L. Promislow

  6. Geriatrics Center, University of Michigan, Ann Arbor, 48109, Michigan, USA.

    Scott D. Pletcher

Authors
  1. Zachary M. Harvanek
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yang Lyu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christi M. Gendron
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jacob C. Johnson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shu Kondo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Daniel E. L. Promislow
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Scott D. Pletcher
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Z.M.H. and S.D.P. conceptualized the project, and Z.M.H., Y.L., D.E.L.P. and S.D.P. designed the experiments. Z.M.H., C.M.G. and J.C.J. performed the in vivo experiments, and Z.M.H., C.M.G. and S.D.P. analysed them. D.E.L.P. performed the metabolomics. Y.L. and S.D.P. analysed the metabolomics data, with input from Z.M.H. and D.E.L.P. S.K. created the NPF mutant used in Fig. 3. Z.M.H., Y.L. and S.D.P. wrote the manuscript, with comments from C.M.G. and D.E.L.P.

Corresponding author

Correspondence to Scott D. Pletcher.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

Supplementary Figures 1–8; Supplementary Tables 1,2 (PDF 609 kb)

Supplementary File 1

Neurometabolomic dataset (XLSX 1208 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Harvanek, Z., Lyu, Y., Gendron, C. et al. Perceptive costs of reproduction drive ageing and physiology in male Drosophila. Nat Ecol Evol 1, 0152 (2017). https://doi.org/10.1038/s41559-017-0152

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41559-017-0152

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing