By Jessica Breznik, Dawn Bowdish (@MsMacrophage) and Deborah Sloboda (@Sloboda_Lab), McMaster University, Hamilton, Canada
Biological sex can have a major impact on a person’s health and risk of disease. For example, sex-related differences in immune response to COVID-19 have led to more deaths in men and possibly more long-term health consequences in women. That is why it’s important for researchers to study the similarities and differences in the physiology of males and females. Despite this, many researchers tend to design studies that only or largely include, male subjects. This is true of both clinical trials involving humans, and pre-clinical research involving animals.
For decades, researchers have believed that females are more challenging to study because hormones and the reproductive cycle might affect their physiological traits, such as their immune system. Some researchers believe that you would have to include females from every stage of the reproductive cycle to account for hormone-driven variability.
More variation means more research subjects need to be included and this (as well as the logistical challenges of determining which stage of the reproductive cycle a woman is in) has led to resistance in using female subjects and a preference for using male subjects to reduce costs and simplify experimental design. This practice has led to major knowledge gaps in approaches for diagnosis and treatment of diseases in females.
Our study published last month in The Journal of Physiology challenges these perceptions and proposes new directions in using females (and males) to understand our immune system..
The number and type of immune cells in the circulation change with age, inflammation, time of day and other factors that we don’t fully understand. Counting the numbers and types of cells (“immunophenotyping”) in the blood is a standard technique used to measure levels of inflammation during health and disease or to measure how drugs and treatments alter the immune response.
We found that when we looked at peripheral blood immune cells in common laboratory mice, it turns out that males are actually more variable, not females. In the end, being male, and not the female reproductive cycle, significantly affected immune cell variability.
In light of our findings, we provided tools for researchers to make informed decisions about study design. These included tables designed to facilitate experiment planning and sample size calculations so that researchers can quickly and accurately determine how many mice, of either sex, are needed to get reproducible results in their studies.
The implications of this discovery could translate to a reduction in the total number of animals being used in research, an increase in the consistency of research results, and a removal of the bias associated with studying females, therefore making clinical trials more effective and efficient.
Please note that all views expressed on The Physiological Society’s blog reflect those of the author(s) and not of The Society.