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.

  • News Feature
  • Published:

Solving for (se)x

Lab Animal volume 44, pages 371–372 (2015)Cite this article

Looking at a mouse or a rat, it can be very hard to tell if it is female or male. But it is clear that there are many and varied differences in the biology of male and female mice and rats, as there are in humans. Most studies in biomedical research, however, only use animals of one sex (most commonly males)1. Recent efforts by the National Institutes of Health (NIH) are trying to change this status quo, with the hope that studying both sexes in biomedical studies will provide valuable insights that will benefit men and women.

In a comment in May 2014, Janine Clayton, Director of the NIH Office of Research on Women's Health, and Francis Collins, Director of the NIH, announced a new policy aimed at increasing the number of female animals used in preclinical studies2. Citing evidence that there is higher prevalence and severity of adverse drug reactions in men than in women3, Clayton and Collins called on the research community to remedy the paucity of studies that include female rodents, saying that “this move is essential, potentially very powerful and need not be difficult or costly.”

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

References

  1. Beery, A.K. & Zucker, I. Sex bias in neuroscience and biomedical research. Neurosci. Biobehav. Rev. 35, 565–572 (2011).

    Article  Google Scholar 

  2. Clayton, J.A. & Collins, F.S. NIH to balance sex in cell and animal studies. Nature 509, 282–283 (2014).

    Article  Google Scholar 

  3. Franconi, F., Brunelleschi, S., Steardo, L. & Cuomo, V. Gender differences in drug responses. Pharmacol. Res. 55, 81–95 (2007).

    Article  CAS  Google Scholar 

  4. National Institutes of Health. Consideration of Sex as a Biological Variable in NIH-funded Research. Notice NOT-OD-15-102. (National Institutes of Health, Washington, DC, 9 June 2015).

  5. Prendergast B.J., Onishi, K.G. & Zucker, I. Female mice liberated for inclusion in neuroscience and biomedical research. Neurosci Biobehav. Rev. 40, 1–5 (2014).

    Article  Google Scholar 

  6. Mogil, J.S. Sex differences in pain and pain inhibition: multiple explanations of a controversial phenomenon. Nat. Rev. Neurosci. 13, 859–866 (2012).

    Article  CAS  Google Scholar 

  7. Sorge, R.E. et al. Different immune cells mediate mechanical pain hypersensitivity in male and female mice. Nat. Neurosci. 18, 1081–1083 (2015).

    Article  CAS  Google Scholar 

  8. Howerton, A.R. et al. Sex differences in corticotropin-releasing factor receptor-1 action within the dorsal raphe nucleus in stress responsivity. Biol. Psychiatry 75, 873–883 (2014).

    Article  CAS  Google Scholar 

  9. Hox, V. et al. Estrogen increases the severity of anaphylaxis in female mice through enhanced endothelial nitric oxide synthase expression and nitric oxide production. J. Allergy Clin. Immunol. 135, 729–736 (2014).

    Article  Google Scholar 

  10. Papenfuss, T.L. et al. Sex differences in experimental autoimmune encephalomyelitis in multiple murine strains. J. Neuroimmunol. 150, 59–69 (2004).

    Article  CAS  Google Scholar 

  11. Wisdom, A.J. et al. Estrogen receptor-β ligand treatment after disease onset is neuroprotective in the multiple sclerosis model. J. Neurosci. Res. 91, 901–908 (2013).

    Article  CAS  Google Scholar 

  12. Dakin, R.S. et al. Estrogens protect male mice from obesity complications and influence glucocorticoid metabolism. Int. J. Obes. doi:10.1038/ijo.2015.102 (published online 2 June 2015).

  13. Penaloza, C. et al. Sex of the cell dictates its response: differential gene expression and sensitivity to cell death inducing stress in male and female cells. FASEB J. 23, 1869–1879 (2009).

    Article  CAS  Google Scholar 

  14. Du, L. et al. Innate gender-based proclivity in response to cytotoxicity and programmed cell death pathway. J. Biol. Chem. 279, 38563–38570 (2004).

    Article  CAS  Google Scholar 

  15. Deasy, B.M. et al. A role for cell sex in stem cell-mediated skeletal muscle regeneration: female cells have higher muscle regeneration efficiency. J. Cell Biol. 177, 73–86 (2007).

    Article  CAS  Google Scholar 

Download references

Authors
  1. Brigitta B. Gundersen
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gundersen, B. Solving for (se)x. Lab Anim 44, 371–372 (2015). https://doi.org/10.1038/laban.876

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/laban.876

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