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The sexual dimorphism dilemma
The sexual dimorphism dilemma
About the study
- Biomedical research predominantly uses mice of one sex because doing otherwise would be more complex and costly, but new research shows that differences in male and female mice could impact results substantially
- The International Mouse Phenotyping Consortium (IMPC) is calling for researchers to use a balanced number of male and female mice in research projects to improve the accuracy of the results.
Hinxton, June 26, 2017 - The sex of animals has an effect on the results of biomedical research and should be considered in design of scientific studies, according to researchers from the Wellcome Trust Sanger Institute, the European Bioinformatics Institute (EMBL-EBI) and the International Mouse Phenotyping Consortium. This statement, published in Nature Communications, is based on the discovery that the differences between male and female mice have an effect that could significantly alter the interpretation of studies using animal models with only one gender (sex).
Notable gender differences
Sex influences the prevalence, course and severity of many diseases and disorders, such as cardiovascular diseases, autoimmune diseases and asthma. Although this is common knowledge, it is not uncommon for researchers to ignore the sex of research subjects, especially in animal studies – mainly for logistical reasons.
Today's research is the largest study quantifying the differences between males and females – known as sexual dimorphism. The collaborators analysed 234 physical characteristics, including body composition metabolic profile, blood components and behavioural traits of more than 50,000 mice.
In approximately 10% of the measurable phenotypes, such as blood pressure or glucose levels, we see significantly different values in males and females
"We incorporated data from ten centres in the world, looking at an equal number of male and female mice," explains Terry Meehan, IMPC Project Coordinator at EMBL-EBI. "We found that in approximately 10% of the measurable phenotypes, such as blood pressure or glucose levels, we see notable sexual dimorphism, meaning significantly different values in male and female mice."
All the data from the study is available to researchers through established resources at EMBL-EBI. The scientists hope that this comprehensive analysis will help researchers find the exact mouse strain they're looking for, avoiding the need to conduct new experiments themselves.
What is sexual dimorphism?
Sexual dimorphism describes distinct physical differences between males and females of the same species (other than the sex organs). Examples include size, colouration, and additional body parts such as antlers or a mane.
Phenotype refers to the physical traits and characteristics of an organism resulting from their genetic makeup. Source: www.yourgenome.org
Sexual dimorphism: the figures
The team found that in the standard, control group of mice, sex had an impact on 56.6 per cent of quantitative traits, such as body weight. The measured impact was 9.9 per cent on qualitative traits, for example whether the shape of the head was normal.
In mice that had a gene switched off – the mutant mice – sex modified the effect of the mutation in up to 17.7 per cent of quantitative traits and 13.3 per cent of qualitative traits.
This study is a major step highlighting the impact of sex differences in research
"It is likely that important scientific information is missed by not investigating more thoroughly how males and females differ in biomedical research," declares Steve Brown, an author of the study and Chair of the IMPC Steering Committee. "Rather than extrapolate the results to account for the opposite sex, these results suggest designing experiments to include both sexes in the study of disease. This study is a major step highlighting the impact of sex differences in research, and will help in accounting for those differences in the future of biomedicine."
Value for clinical research
This study has implications for the design of future animal studies and clinical trials. More than 20 years ago, the NIH changed its rules so that all clinical research in the US has to include both sexes. Nevertheless, women are still underrepresented and preclinical trials are still done predominantly in males.
"This was a scientific blind spot that we really thought needed exploration," says Natasha Karp, lead author who carried out the research at the Wellcome Trust Sanger Institute, and now works in the IMED Biotech Unit at AstraZeneca. "A person's sex has a significant impact on the course and severity of many common diseases, and the consequential side effects of treatments – which are being missed. Now we have a quantitative handle on how much sexual dimorphism has an impact in biomedical research. In the movement towards precision medicine, we not only have to account for genetic differences between people when we consider disease, but also their sex."
KARP, N, et al. (2017). Prevalence of sexual dimorphism in mammalian phenotypic traits. Nature Communications. Published online 26 June; DOI: 10.1038/ncomms15475/ncomms15475
This work was supported by Wellcome, the National Institutes of Health and others. For full funding information, please see the paper.
About the IMPC
The International Mouse Phenotyping Consortium aims to produce and phenotype knockout mouse lines for 20,000 genes. Through this activity and employing data annotation tools systematically, the consortium aims to discover and ascribe biological function to each gene, driving new ideas and underpinning future research into biological systems. The IMPC’s centralised data resource offers free, unrestricted access to primary and secondary data by the scientific community, promoting sharing of data, genotype-phenotype annotation, standard operating protocols, and the development of open source data analysis tools. www.mousephenotype.org
Image credit: Spencer Phillips, EMBL-EBI