Genotoxic effect of restraint and stress pheromone on somatic and germ cells of mouse males Mus musculus L.

Cover Page

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access


BACKGROUND: Different stressors affect the genome integrity, but the mechanisms of such action are underexplored.

MATERIALS AND METHODS: Bone marrow and testicular cells of CBA and CD-1 mouse males were used to estimate their genome integrity after stressor action by the comet assay.

RESULTS: It is shown here that restraint and 2,5-dimethylpyrazine both increase damaged cell frequency in bone marrow as well as in testes of mouse males. For the first time the effect of immobilization and 2,5-dimethylpyrazine in testicular cells is demonstrated using the comet assay. Both stressors have similar effects in cells of both tissues analyzed.

CONCLUSION: Mechanisms of the effects and possible role in microevolution are under discussion.

Full Text

Restricted Access

About the authors

Veronika D. Shcherbinina

Saint Petersburg State University

ORCID iD: 0000-0002-4813-736X

Graduate student

Russian Federation, Saint Petersburg

Marina V. Petrova

Institute of Higher Nervous Activity and Neurophysiology of RAS

ORCID iD: 0000-0003-4385-7509

PhD, Cand. Sci. (Biol.)

Russian Federation, Moscow

Timofey S. Glinin

Saint Petersburg State University

ORCID iD: 0000-0003-0550-741X
SPIN-code: 2549-2759

PhD, Cand. Sci. (Biol.)

Russian Federation, Saint Petersburg

Eugene V. Daev

Saint Petersburg State University; Pavlov Institute of Physiology of the RAS

Author for correspondence.
ORCID iD: 0000-0003-2036-6790

PhD, Dr. Sci. (Biol.)

Russian Federation, Saint Petersburg; Saint Petersburg


  1. Selye H. The physiology and pathology of exposure to stress. Montreal: Acta Med. Publ., 1950. 203 p.
  2. Chitty D. Population processes in the vole and their relevance to general theory. Can J Zool. 1960;38(1),99–113. doi: 10.1139/z60-011
  3. Hoffmann AA, Hercus MJ. Environmental stress as an evolutionary force. BioScience. 2000;50(3):217. doi: 10.1641/0006-3568(2000)050[0217: ESAAEF]2.3.CO;2
  4. Daev EV. Genetic aspects of stress neuroendocrinology. In: Neuroendocrinology research developments. Penkava NS, Haight LR, editors. NY: Nova Science Publishers, 2010. 119–133 p.
  5. Zhou P, Lian HY, Cui W, et al. Maternal-restraint stress increases oocyte aneuploidy by impairing metaphase I spindle assembly and reducing spindle assembly checkpoint proteins in mice. Biol Reprod. 2012;86(3):83. doi: 10.1095/biolreprod.111.095281
  6. Selye H. A syndrome produced by diverse nocuous agents. 1936. J Neuropsychiatry Clin Neurosci. 1998;10(2):230–231. doi: 10.1176/jnp.10.2.230a
  7. Owusu-Ansah E, Perrimon N. Stress signaling between organs in metazoa. Annu Rev Cell Dev Biol. 2015;31:497–522. doi: 10.1146/annurev-cellbio-100814-125523
  8. Daev EV. Stress, chemocommunication, and the physiological hypothesis of mutation. Russian Journal of Genetics. 2007;43(10):1082–1092. (In Russ.) doi: 10.1134/s102279540710002x
  9. Dayas CV, Buller KM, Crane JW, et al. Stressor categorization: acute physical and psychological stressors elicit distinctive recruitment patterns in the amygdala and in medullary noradrenergic cell groups. Eur J Neurosci. 2001;14(7):1143–1152. doi: 10.1046/j.0953-816x.2001.01733.x
  10. Bowers SL, Bilbo SD, Dhabhar FS, Nelson RJ. Stressor-specific alterations in corticosterone and immune responses in mice. Brain Behav Immun. 2008;22(1):105–113. doi: 10.1016/j.bbi.2007.07.012
  11. Novotny M, Jemiolo B, Harvey S, et al. Adrenal-mediated endogenous metabolites inhibit puberty in female mice. Science. 1986;231(4739):722–725. doi: 10.1126/science.3945805
  12. Koyama S. Primer effects by conspecific odors in house mice: a new perspective in the study of primer effects on reproductive activities. Horm Behav. 2004;46(3):303–310. doi: 10.1016/j.yhbeh.2004.03.002
  13. Daev EV, Vorob’ev KV, Shustova TI, et al. Genotipspetsificheskie izmeneniya nekotorykh funktsional’nykh pokazatelei immunokompetentnykh kletok u samtsov laboratornykh myshei v usloviyakh feromonal’nogo stressa. Russian Journal of Genetics. 2000;36(8):872–876.
  14. Glinin TS. Puti stabilizatsii i destabilizatsii genoma kletok kostnogo mozga myshi pri deistvii ol’faktornykh khemosignalov [dissertation]. Saint Petersburg: 2018. 175 p. (In Russ.)
  15. Dyuzhikova NA, Daev EV. Genome and stress-reaction in animals and humans. Ecological genetics. 2018;16(1):4–26. (In Russ.) doi: 10.17816/ecogen1614-26
  16. Dobrzyńska MM. The effects in mice of combined treatments to X-rays and antineoplastic drugs in the Comet assay. Toxicology. 2005;207(2):331–338. doi: 10.1016/j.tox.2004.10.002
  17. Higashimoto M, Isoyama N, Ishibashi S, et al. Preventive effects of metallothionein against DNA and lipid metabolic damages in dyslipidemic mice under repeated mild stress. J Med Invest. 2013;60(3–4):240–248. doi: 10.2152/jmi.60.240
  18. Durnev AD, Zhanataev AK, Anisina EA, et al. Primenenie metoda shchelochnogo gel’-ehlektroforeza izolirovannykh kletok dlya otsenki genotoksicheskikh svoistv prirodnykh i sinteticheskikh soedinenii: metodicheskie rekomendatsii. Moscow: 2006. 27 p. (In Russ.)
  19. Fischman HK, Pero RW, Kelly DD. Psychogenic stress induces chromosomal and DNA damage. Int J Neurosci. 1996;84(1–4): 219–227. doi: 10.3109/00207459608987267
  20. El-Refaiy AI, El-Desouki NI, Abdel-Azeem H, Elbaely MM. Cytogenetical study on the Effect of Immobilization Stress on Albino Rat and the Ameliorative Role of Diazepam. Current Science International. 2017;6(4):900–907.
  21. Malvandi AM, Haddad F, Moghimi A. Acute restraint stress increases the frequency of vinblastine-induced micronuclei in mouse bone marrow cells. Stress. 2010;13(3):276–280. doi: 10.3109/10253890903296710
  22. Hara MR, Kovacs JJ, Whalen EJ, et al. A stress response pathway regulates DNA damage through β2-adrenoreceptors and β-arrestin-1. Nature. 2011;477(7364):349–353. doi: 10.1038/nature10368
  23. Mikhailov VM, Vezhenkova IV. Double-strand breaks of DNA of C57BL and mdx mouse cardiomyocytes after dynamic stress. Cell Tiss Biol. 2007;1:328–333. doi: 10.1134/S1990519X07040049
  24. Aguilera A, García-Muse T. Causes of genome instability. Annu Rev Genet. 2013;47:1–32. doi: 10.1146/annurev-genet-111212-133232
  25. Daev EV, Dukelskaya AV. The female pheromone 2,5-dimethylpyrazine induces sperm-head abnormalities in male CBA mice. Russian Journal of Genetics. 2003;39(7):811–815. doi: 10.1023/A:1024709321888
  26. Daev EV, Dukelskaya AV. Induction of meiotic disturbances in spermatocytes i by pheromones as an inhibiting mechanism of male reproductive function in house mice. Cell and Tissue Biology. 2005;47(6):505–509. (In Russ.)
  27. Daev EV, Petrova MV, Onopa LS, et al. DNA damage in bone marrow cells of mouse males in vivo after exposure to the pheromone: Comet assay. Russian Journal of Genetics. 2017;53(10): 1105–1112. (In Russ.) doi: 10.1134/s1022795417100027
  28. Jemiolo B, Novotny M. Inhibition of sexual maturation in juvenile female and male mice by a chemosignal of female origin. Physiol Behav. 1994;55(3):519–522. doi: 10.1016/0031-9384(94)90110-4
  29. Borodin PM, Belyaev DK. Vliyanie stressa na chastotu krossingovera vo 2-i khromosome domovoi myshi. Doklady AN SSSR. 1980;253(3):727–729. (In Russ.)
  30. Borodin PM, Belyaev DK. Vliyanie ehmotsional’nogo stressa na chastotu rekombinatsii v 1-i khromosome domovoi myshi. Doklady AN SSSR. 1986;286(3):726–728. (In Russ.)
  31. Lobashev ME. Fiziologicheskaya (paranekroticheyskaya) gipoteza mutatsionnogo protsessa. Pushkin Leningrad state university journal. 1947;8:10–29. (In Russ.)
  32. Markel AL. Behavior, stress, and evolution. Filosofiya nauki. 2013;56(1):140–152. (In Russ.)
  33. Hodes GE, Pfau ML, Leboeuf M, et al. Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress. PNAS USA. 2014;111(45):16136–16141. doi: 10.1073/pnas.1415191111
  34. Jiang W, Li Y, Wei W, et al. Spleen contributes to restraint stress induced hepatocellular carcinoma progression. Int Immunopharmacol. 2020;83:106420. doi: 10.1016/j.intimp.2020.106420
  35. Acevedo-Whitehouse K, Duffus AL. Effects of environmental change on wildlife health. Philos Trans R Soc Lond B Biol Sci. 2009;364(1534):3429–3438. doi: 10.1098/rstb.2009.0128
  36. Brown RE. Mammalian Social Odors: A Critical Review. Adv Study Behav. 1979;10:104–143. doi: 10.1016/S0065-3454(08)60094-7
  37. Brennan PA, Kendrick KM. Mammalian social odours: attraction and individual recognition. Philos Trans R Soc Lond B Biol Sci. 2006;361(1476):2061–2078. doi: 10.1098/rstb.2006.1931

Supplementary files

Supplementary Files
1. Fig. 1. Degree of DNA damage in testes cells of male CD-1 mice after exposure to two different stressors (Me; Range: Min to Max)

Download (68KB)
2. Fig. 2. Exponential distribution of damaged testicular cells accordingly DNA content in comet tails (Y0 e(–KX); 95%CI) of mouse males of control group (H2O) (1), and positive control group (males injected with mitomycin C) (2). Parameters Y0 and F0.5 are specified. Data from the first experiment

Download (92KB)
3. Fig. 3. Frequency distribution of testicular cells with different DNA content in comet tails (Y0e(–KX); 95%CI) after 2 hrs exposure of CD-1 mouse males to different stressors. 1 – control; 2 – restraint stress; 3 – 2,5-dimethylpyrazine

Download (140KB)
4. Fig. 4. Degree of DNA damage in bone marrow cells of male CBA mice after exposure to two different stressors (Me; Range: Min to Max)

Download (80KB)
5. Fig. 5. Frequency distribution of bone marrow cells with different DNA content in comet tails after 2 hrs exposure of CBA mouse males to different stressors. 1 – control; 2 – restraint stress; 3 –2,5-dimethylpyrazine

Download (143KB)



Abstract: 142

PDF (Russian): 5

PDF (English): 2


Article Metrics

Metrics Loading ...


Copyright (c) 2021 ООО "Эко-Вектор"

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies