Mitochondrial physiology varies with parity and body mass in the laboratory mouse (Mus musculus)

Abstract

The life-history patterns that animals display are a product of their ability to maximize reproductive performance while concurrently balancing numerous metabolic demands. For example, the energetic costs of reproduction may reduce an animal’s ability to support self-maintenance and longevity. In this work, we evaluated the impact of parity on mitochondrial physiology in laboratory mice. The theory of mitohormesis suggests that modest exposure to reactive oxygen species can improve performance, while high levels of exposure are damaging. Following this theory, we hypothesized that females that experienced one bout of reproduction (primiparous) would display improved mitochondrial capacity and reduced oxidative damage relative to non-reproductive (nulliparous) mice, while females that had four reproductive events (multiparous) would have lower mitochondrial performance and greater oxidative damage than both nulliparous and primiparous females. We observed that multiple reproductive events enhanced the mitochondrial respiratory capacity of liver mitochondria in females with high body mass. Four-bout females showed a positive relationship between body mass and mitochondrial capacity. In contrast, non-reproductive females showed a negative relationship between body mass and mitochondrial capacity and primiparous females had a slope that did not differ from zero. Other measured variables, too, were highly dependent on body mass, suggesting that a female’s body condition has strong impacts on mitochondrial physiology. We also evaluated the relationship between how much females allocated to reproduction (cumulative mass of all young weaned) and mitochondrial function and oxidative stress in the multiparous females. We found that females that allocated more to reproduction had lower basal respiration (state 4), lower mitochondrial density, and higher protein oxidation in liver mitochondria than females that allocated less. These results suggest that, at least through their first four reproductive events, female laboratory mice may experience bioenergetic benefits from reproduction but only those females that allocated the most to reproduction appear to experience a potential cost of reproduction.

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References

  1. Ajmera VH, Terrault NA, VanWagner LB et al (2019) Longer lactation duration is associated with decreased prevalence of non-alcoholic fatty liver disease in women. J Hepatol 70:126–132. https://doi.org/10.1016/j.jhep.2018.09.013

    Article  PubMed  Google Scholar 

  2. Balaban RS, Nemoto S, Finkel T (2005) Mitochondria, oxidants, and aging. Cell 120:483–495. https://doi.org/10.1016/J.CELL.2005.02.001

    CAS  Article  PubMed  Google Scholar 

  3. Bell AW, Bauman DE (1997) Adaptations of glucose metabolism during pregnancy and lactation. J Mammary Gland Biol Neoplasia 2:265–278

    CAS  Article  Google Scholar 

  4. Blount JD, Vitikainen EIK, Stott I, Cant MA (2016) Oxidative shielding and the cost of reproduction. Biol Rev 91:483–497. https://doi.org/10.1111/brv.12179

    Article  PubMed  Google Scholar 

  5. Bradford MM (1976) Rapid and sensitive method for quantitation of microgram quantities of protein utilizing principle of protein-dye binding. Anal Biochem 72:248–254. https://doi.org/10.1006/abio.1976.9999

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. Brady LJ, Brady PS, Romsos DR, Hoppel CL (1985) Elevated hepatic mitochondrial and peroxisomal oxidative capacities in fed and starved adult obese (ob/ob) mice. Biochem J 231:439–444. https://doi.org/10.1042/bj2310439

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  7. Brand MD (2000) Uncoupling to survive? The role of mitochondrial inefficiency in ageing. Exp Gerontol 35:811–820. https://doi.org/10.1016/s0531-5565(00)00135-2

    CAS  Article  PubMed  Google Scholar 

  8. Brand MD, Turner N, Ocloo A, Else PL, Hulbert AJ (2003) Proton conductance and fatty acyl composition of liver mitochondria correlates with body mass in birds. Biochem J 376(3):741–748

    CAS  Article  Google Scholar 

  9. Bratic A, Larsson NG (2013) The role of mitochondria in aging. J Clin Investig 123:951–957. https://doi.org/10.1172/JCI64125

    CAS  Article  PubMed  Google Scholar 

  10. Brett K, Ferraro Z, Yockell-Lelievre J et al (2014) Maternal-fetal nutrient transport in pregnancy pathologies: the role of the placenta. Int J Mol Sci 15:16153–16185. https://doi.org/10.3390/ijms150916153

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. Costantini D (2014) Oxidative stress and hormesis in evolutionary ecology and physiology: a marriage between mechanistic and evolutionary approaches. Springer, Berlin  

  12. Costantini D, Casasole G, AbdElgawad H et al (2016) Experimental evidence that oxidative stress influences reproductive decisions. Funct Ecol 30:1169–1174. https://doi.org/10.1111/1365-2435.12608

    Article  Google Scholar 

  13. Dobson FS, Risch TS, Murie JO (1999) Increasing returns in the life history of Columbian ground squirrels. J Anim Ecol 68:73–86

    Article  Google Scholar 

  14. Flatt T, Heyland A (2011) Mechanisms of Life history evolution, the genetics and physiology of life history traits and trade-offs. Oxford University Press, Oxford

    Google Scholar 

  15. Hammond KA, Diamond J (1997) Maximal sustained energy budgets in humans and animals. Nature 386:457–462. https://doi.org/10.1038/386457a0

    CAS  Article  PubMed  Google Scholar 

  16. Heidinger BJ, Blount JD, Boner W et al (2012) Telomere length in early life predicts lifespan. Proc Natl Acad Sci 109:1743–1748

    CAS  Article  Google Scholar 

  17. Hood WR, Zhang Y, Mowry AV et al (2018) Life history trade-offs within the context of mitochondrial hormesis. Integr Comp Biol. https://doi.org/10.1093/icb/icy073

    Article  PubMed  PubMed Central  Google Scholar 

  18. Hood WR, Williams AS, Hill GE (2019) An ecologists’ guide to mitochondrial DNA mutations and senescence. Integr Comp Biol. https://doi.org/10.1093/icb/icz097

    Article  PubMed  Google Scholar 

  19. Hyatt HW, Zhang Y, Hood WR, Kavazis AN (2017) Lactation has persistent effects on a mother’s metabolism and mitochondrial function. Sci Rep. https://doi.org/10.1038/s41598-017-17418-7

    Article  PubMed  PubMed Central  Google Scholar 

  20. Hyatt HW, Zhang Y, Hood WR, Kavazis AN (2018) Physiological, mitochondrial, and oxidative stress differences in the presence or absence of lactation in rats. Reprod Biol Endocrinol 16:2–14. https://doi.org/10.1186/s12958-017-0317-7

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. Itsara LS, Kennedy SR, Fox EJ et al (2014) Oxidative stress is not a major contributor to somatic mitochondrial DNA mutations. PLoS Genet. https://doi.org/10.1371/journal.pgen.1003974

    Article  PubMed  PubMed Central  Google Scholar 

  22. Kavazis AN, Talbert EE, Smuder AJ, Hudson MB, Nelson WB, Powers SK (2009) Mechanical ventilation induces diaphragmatic mitochondrial dysfunction and increased oxidant production. Free Radical Biol Med 46(6):842–850

    CAS  Article  Google Scholar 

  23. Keech MA, Bowyer RT, Ver Hoef JM et al (2000) Life-history consequences of maternal condition in Alaskan moose. J Wildl Manag 64:450–462

    Article  Google Scholar 

  24. Kirkwood TBL, Rose MR (1991) Evolution of senescene—late survival sacrificed for reproduction. Philos Trans R Soc Lond Ser B Biol Sci 332:15–24

    CAS  Article  Google Scholar 

  25. Larsen S, Nielsen J, Hansen CN et al (2012) Biomarkers of mitochondrial content in skeletal muscle of healthy young human subjects. J Physiol 590:3349–3360. https://doi.org/10.1113/jphysiol.2012.230185

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  26. Larsson N-G, Words K, Larsson N-G (2010) Somatic mitochondrial DNA mutations in mammalian aging. Annu Rev Biochem 79:683–706. https://doi.org/10.1146/annurev-biochem-060408-093701

    CAS  Article  PubMed  Google Scholar 

  27. Mélanie B, Caroline R, Yann V, Damien R (2019) Allometry of mitochondrial efficiency is set by metabolic intensity. Proc Roy Soc B Biol Sci 286(1911):20191693

    Google Scholar 

  28. Metcalfe NB, Monaghan P (2013) Does reproduction cause oxidative stress? An open question. Trends Ecol Evol 28:347–350. https://doi.org/10.1016/j.tree.2013.01.015

    Article  PubMed  Google Scholar 

  29. Monaghan P, Charmantier A, Nussey DH, Ricklefs RE (2008) The evolutionary ecology of senescence. Wiley, New York

    Google Scholar 

  30. Monaghan P, Metcalfe NB, Torres R, Dev S (2009) Oxidative stress as a mediator of life history trade-offs: mechanisms, measurements and interpretation. Ecol Lett 12:75–92. https://doi.org/10.1111/j.1461-0248.2008.01258.x

    Article  PubMed  Google Scholar 

  31. Mowry AV, Kavazis AN, Sirman AE et al (2016) Reproduction does not adversely affect liver mitochondrial respiratory function but results in lipid peroxidation and increased antioxidants in house mice. PLoS ONE 11:e0160883. https://doi.org/10.1371/journal.pone.0160883

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. Newman S, Harris DL, Doolittle DP (1985) Lifetime parental productivity in twenty-seven crosses of mice. II. Weaning traits reflecting reproduction and lactation. J Sci 61:367–375. https://doi.org/10.2527/jas1985.612367x

    CAS  Article  Google Scholar 

  33. Ojaimi J, Masters CL, Opeskin K et al (1999) Mitochondrial respiratory chain activity in the human brain as a function of age. Mech Ageing Dev 111:39–47. https://doi.org/10.1016/S0047-6374(99)00071-8

    CAS  Article  PubMed  Google Scholar 

  34. Oldakowski L, Piotrowska Z, Chrzascik KM, Sadowska ET, Koteja P, Taylor JRE (2012) Is reproduction costly? No increase of oxidative damage in breeding bank voles. J Exp Biol 215(11):1799–1805

    Article  Google Scholar 

  35. Plumel MI, Stier A, Thiersé D et al (2014) Litter size manipulation in laboratory mice: an example of how proteomic analysis can uncover new mechanisms underlying the cost of reproduction. Front Zool 11:1–13. https://doi.org/10.1186/1742-9994-11-41

    CAS  Article  Google Scholar 

  36. Reznick D, Nunney L, Tessier A (2000) Big houses, big cars, superfleas and the costs of reproduction. Trends Ecol Evol 15:421–425

    CAS  Article  Google Scholar 

  37. Ristow M, Schmeisser K (2014) Mitohormesis: promoting health and lifespan by increased levels of reactive oxygen species (ROS). Dose Response 12:288–341. https://doi.org/10.2203/dose-response.13-035.Ristow

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  38. Roussel D, Salin K, Dumet A, Romestaing C, Rey B, Voituron Y (2015) Oxidative phosphorylation efficiency, proton conductance and reactive oxygen species production of liver mitochondria correlates with body mass in frogs. J Exper Biol 218(20):3222–3228

    Article  Google Scholar 

  39. RStudio Team (2019) RStudio: Integrated Development for R. RStudio, Inc, Boston, MA

  40. Schmidt CM, Hood WR (2016) Female white-footed mice (Peromyscus leucopus) trade off offspring skeletal quality for self-maintenance when dietary calcium intake is low. J Exp Zool Part A Ecol Genet Physiol. https://doi.org/10.1002/jez.2051

    Article  Google Scholar 

  41. Short KR, Bigelow ML, Kahl J et al (2005) Decline in skeletal muscle mitochondrial function with aging in humans. Proc Natl Acad Sci 102:5618–5623. https://doi.org/10.1073/pnas.0501559102

    CAS  Article  PubMed  Google Scholar 

  42. Skogland T (1989) Natural selection of wild reindeer life history traits by food limitation and predation. Oikos 55:101–110. https://doi.org/10.2307/3565879

    Article  Google Scholar 

  43. Speakman JR, Garratt M (2014) Oxidative stress as a cost of reproduction: beyond the simplistic trade-off model. BioEssays 36:93–106. https://doi.org/10.1002/bies.201300108

    Article  PubMed  Google Scholar 

  44. Speakman JR, McQueenie J (1996) Limits to sustained metabolic rate: the link between food intake, basal metabolic rate, and morphology in reproducing mice, Mus musculus. Physiol Zool 69:746–769

    Article  Google Scholar 

  45. Speakman JR, Król E, Johnson MS (2004a) The functional significance of individual variation in basal metabolic rate. Physiol Biochem Zool 77(6):900–915

    Article  Google Scholar 

  46. Speakman JR, Talbot DA, Selman C, Snart S, McLaren JS, Redman P, Krol E, Jackson DM, Johnson MS, Brand MD (2004b) Uncoupled and surviving: individual mice with high metabolism have greater mitochondrial uncoupling and live longer. Aging Cell 3(3):87–95

    CAS  Article  Google Scholar 

  47. Spinazzi M, Casarin A, Pertegato V et al (2012) Assessment of mitochondrial respiratory chain enzymatic activities on tissues and cultured cells. Nat Protoc 7:1235. https://doi.org/10.1038/nprot.2012.058

    CAS  Article  PubMed  Google Scholar 

  48. Stearns SC (1989) Trade-offs in life-history evolution. Funct Ecol 3:259–268. https://doi.org/10.2307/2389364

    Article  Google Scholar 

  49. Stier A, Reichert S, Massemin S et al (2012) Constraint and cost of oxidative stress on reproduction: correlative evidence in laboratory mice and review of the literature. Front Zool 9:37. https://doi.org/10.1186/1742-9994-9-37

    Article  PubMed  PubMed Central  Google Scholar 

  50. Tapia PC (2006) Sublethal mitochondrial stress with an attendant stoichiometric augmentation of reactive oxygen species may precipitate many of the beneficial alterations in cellular physiology produced by caloric restriction, intermittent fasting, exercise and dietary p. Med Hypotheses 66:832–843. https://doi.org/10.1016/j.mehy.2005.09.009

    CAS  Article  PubMed  Google Scholar 

  51. van Noordwijk AJ, de Jong G (1986) Acquisition and allocation of resources: their influence on variation in life history tactics. Am Nat 128:137–142. https://doi.org/10.1086/284547

    Article  Google Scholar 

  52. Williams GC (1957) Pleiotropy, natural selection, and the evolution of senescence. Evolution (N Y) 11:13. https://doi.org/10.2307/2406060

    Article  Google Scholar 

  53. Williams GC (1966) Natural selection, the costs of reproduction, and a refinement of Lack’s principle. Am Nat 100:687–690

    Article  Google Scholar 

  54. Wolf NS, Austad S (2010) Introduction: lifespans and pathologies present at death in laboratory animals. In: The comparative biology of aging. Springer, Berlin, pp 1–26

  55. Yen T-C, Chen Y-S, King K-L et al (1989) Liver mitochondrial respiratory functions decline with age. Biochem Biophys Res Commun 165:994–1003

    Article  Google Scholar 

  56. Zera AJ, Harshman LG (2001) The physiology of lIfe history trade-offs in animals. Annu Rev Ecol Syst 32:95–126. https://doi.org/10.1146/annurev.ecolsys.32.081501.114006

    Article  Google Scholar 

  57. Zhang Y, Hood WR (2016) Current versus future reproduction and longevity: a re-evaluation of predictions and mechanisms. J Exp Biol 219:3177–3189. https://doi.org/10.1242/jeb.132183

    Article  PubMed  PubMed Central  Google Scholar 

  58. Zhang Y, Kallenberg C, Hyatt HW et al (2017) Change in the lipid transport capacity of the liver and blood during reproduction in rats. Front Physiol. https://doi.org/10.3389/fphys.2017.00517

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We would like to thank the Hood lab undergraduates who assisted in data acquisition, analysis and maintaining the mice: Mary Kash, Sam Lubor, Kirkland Bradshaw, Catherine Christian, and Rachel Castor. We would also like to thank members of the Hood and Hill labs for their comments on an earlier version of this manuscript and Todd Steury for advice on the statistical analyses. This work was supported by the National Science Foundation Grants IOS1453784 and OIA1736150.

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Park, N.R., Taylor, H.A., Andreasen, V.A. et al. Mitochondrial physiology varies with parity and body mass in the laboratory mouse (Mus musculus). J Comp Physiol B 190, 465–477 (2020). https://doi.org/10.1007/s00360-020-01285-2

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Keywords

  • Reproduction
  • Life history
  • Oxidative stress
  • Mitochondrial function
  • RCR