Considering sex as a biological variable in preclinical research.
In June 2015, the National Institutes of Health (NIH) released a Guide notice (NOT-OD-15-102) that highlighted the expectation of the NIH that the possible role of sex as a biologic variable be factored into research design, analyses, and reporting of vertebrate animal and human studies. Anticipating these guidelines, the NIH Office of Research on Women's Health, in October 2014, convened key stakeholders to discuss methods and techniques for integrating sex as a biologic variable in preclinical research. The workshop focused on practical methods, experimental design, and approaches to statistical analyses in the use of both male and female animals, cells, and tissues in preclinical research. Workshop participants also considered gender as a modifier of biology. This article builds on the workshop and is meant as a guide to preclinical investigators as they consider methods and techniques for inclusion of both sexes in preclinical research and is not intended to prescribe exhaustive/specific approaches for compliance with the new NIH policy.-Miller, L. R., Marks, C., Becker, J. B., Hurn, P. D., Chen, W.-J., Woodruff, T., McCarthy, M. M., Sohrabji, F., Schiebinger, L., Wetherington, C. L., Makris, S., Arnold, A. P., Einstein, G., Miller, V. M., Sandberg, K., Maier, S., Cornelison, T. L., Clayton, J. A. Considering sex as a biological variable in preclinical research.
Office of Research on Women's Health, National Institutes of Health, Bethesda, Maryland, USA; leah.miller@nih.gov.
Leah R
LR
Miller
Division of Cancer Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Cheryl
C
Marks
Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, Michigan, USA.
Jill B
JB
Becker
School of Nursing, University of Michigan, Ann Arbor, Michigan, USA.
Patricia D
PD
Hurn
Department of Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center, Bryan, Texas, USA.
Wei-Jung
WJ
Chen
Women's Health Research Institute, Northwestern University, Chicago, Illinois, USA.
Teresa
T
Woodruff
Department of Pharmacology, University of Maryland, Baltimore, Maryland, USA.
Margaret M
MM
McCarthy
Department of Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center, Bryan, Texas, USA.
Farida
F
Sohrabji
History of Science, Stanford University, Stanford, California, USA.
Londa
L
Schiebinger
National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland, USA.
Cora Lee
CL
Wetherington
Office of Research and Development, National Center for Environmental Assessment, U.S. Environmental Protection Agency, Washington, D.C., USA.
Susan
S
Makris
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, California, USA.|Laboratory of Neuroendocrinology of the Brain Research Institute, University of California, Los Angeles, Los Angeles, California, USA.
Arthur P
AP
Arnold
Department of Psychology, University of Toronto, Toronto, Ontario, Canada.|The Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.|Women's College Research Institute, Toronto, Ontario, Canada.
Gillian
G
Einstein
Department of Surgery and Physiology, Mayo Clinic, Rochester, Minnesota, USA.|Department of Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, USA.
Virginia M
VM
Miller
Department of Medicine, Georgetown University Medical Center, Washington, D.C., USA.|Center for the Study of Sex Differences in Health, Aging and Disease, Georgetown University Medical Center, Washington, D.C., USA.
Kathryn
K
Sandberg
Office of Research on Women's Health, National Institutes of Health, Bethesda, Maryland, USA.
Susan
S
Maier
Office of Research on Women's Health, National Institutes of Health, Bethesda, Maryland, USA.
Terri L
TL
Cornelison
Office of Research on Women's Health, National Institutes of Health, Bethesda, Maryland, USA.
Janine A
JA
Clayton
D035843:Biomedical Research / Q000592:standards*; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D008297:Male; D009316:National Institutes of Health (U.S.) / Q000592:standards*; D012737:Sex Factors; D014481:United States
gender; methods; sex differences; sex influences
Nature. 2010 Jun 10;465(7299):690
20535186
Nat Rev Cancer. 2011 Feb;11(2):135-41
21258397
Endocr Rev. 1999 Jun;20(3):279-307
10368772
Nat Neurosci. 2011 Jun;14(6):677-83
21613996
Endocrinology. 2005 Apr;146(4):1650-73
15618360
Nature. 2014 Jan 30;505(7485):612-3
24482835
Clin Cancer Res. 2009 Oct 15;15(20):6358-66
19825954
Cardiovasc Res. 2014 Jun 1;102(3):375-84
24654234
FASEB J. 2016 Feb;30(2):519-24
26514164
ILAR J. 2014;55(3):383-91
25541540
Dev Dyn. 2013 Apr;242(4):371-9
23361913
Genome Biol. 2015 Feb 10;16:28
25886764
Front Neuroendocrinol. 2014 Oct;35(4):405-19
24388960
Exp Neurol. 2014 Sep;259:2-9
24509348
J Biol Chem. 2004 Sep 10;279(37):38563-70
15234982
J Neurosci. 2012 Feb 15;32(7):2241-7
22396398
PLoS Biol. 2015 Jun 09;13(6):e1002165
26057340
Nature. 2012 Oct 11;490(7419):187-91
23060188