The American Physiological Society Press Release

“The Sex of Cells” in the Lab

Why identifying sex differences in cells and other lab materials is key to better research results

Bethesda, Md. (Jan. 2, 2014)—In almost every successful enterprise there is a guiding principle that states “Don’t overlook anything, no matter how small.”  For more than 125 years, physiologists—scientists who study the branch of biology that deals with the functions and activities of life or of living matter such as cells, tissues, and organs—have followed that advice, but their scientific society, the American Physiological Society (APS), recently provided a new mandate about an aspect that is often overlooked in research studies.

What the APS did in 2012 was to require authors to take into account the sex of the cell lines, biological materials and animals used in their experiments. 

At first glance this requirement may appear to be excessive because one might think that a cell lacks features that would reflect its sex or gender. In fact, that is not true.  Researchers are now discovering that the sex of experimental subjects—even cells—does matter in research. This concept, which is supported by many experimental findings, has been emphasized by the Institute of Medicine (IOM) of the U.S. National Academies in noting that sex differences important to health and human disease occur at conception and throughout the life span, affecting behavior, perception, and health.

Sex vs. Gender

Authors of articles that describe studies to be published in APS-sponsored journals were advised to examine new IOM definitions on sex and gender and to inform readers of their articles about the sex of the biological material used in the study.   “Sex” is an important biological feature that is dictated by the presence of sex chromosomes; every cell has a “sex”.  On the other hand, “gender” is a cultural concept referring to behaviors that might result from environmental stimuli or psychosocial expectations.

Identifying the sex or gender may clear away confusion related to differing results that are obtained by scientists who conduct similar experiments—even ones supposedly conducted under identical conditions—but often with different types of cells. 

The idea that sex matters is leading to new looks at old assumptions in several fields.  Cell physiology, the study of cell function and interaction in its environment, is one area where work has been done to establish the role of sex in biology.  Evidence indicates that male cells (which have X and Y chromosomes) may not behave the same way as do female cells (that have 2 X chromosomes).

“I Don’t Know the Question, but Sex is Definitely the Answer!”

An article summarizing the efforts to determine the way in which sex impacts cell physiological research has been written by Catherine M. Fuller, of the Department of Cell, Developmental and Integrative Biology at the University of Alabama-Birmingham, and Paul A. Insel of the Departments of Pharmacology and Medicine at the University of California-San Diego. Paul Insel is also the Editor-in-Chief of the American Journal of Physiology-Cell Physiology (AJP- Cell). Their article is entitled (with apologies to Woody Allen), “I don't know the question, but sex is definitely the answer! Focus on “In pursuit of scientific excellence: sex matters” and "Do you know the sex of your cells?" It is online at Their article examines two recent articles published in AJP-Cell and one in Nature that provide a compelling case on why the APS action undertaken in 2012 was not only correct but essential.

Drs. Fuller and Insel suggest that “In pursuit of scientific excellence: sex matters,” the editorial that introduced the new APS policy on sex and gender, provides an essential framework on why this step was taken.  Written by Virginia M. Miller, a Professor at the Mayo Clinic College of Medicine, the editorial ( describes why the policy change would benefit the scientific community and ultimately human health. 

An additional evaluation of how sex differences in cell physiology impact cell regulation, stem cell function and clinical and pharmaceutical science was undertaken by Elizabeth Pollitzer, Director, Portia Ltd., in the United Kingdom.  Her findings were presented before the third National Science Foundation sponsored Gender Summit held in Washington, D.C. in November 2013.  Her article, “Cell Sex Matters,” appeared in the online edition of Nature.  

“Do You Know the Sex of Your Cells?”

The third article, “Do you know the sex of your cells?”  ( is by Kalpit Shah, Charles E. McCormack and Neil A. Bradbury, of the Department of Physiology and Biophysics at the Chicago Medical School. Their article, published in the January 1, 2014 edition of AJP-Cell, explores sex from the point of view of chromosomal differences, the role of genes that express differently in males and females and the impact of these differences on the biology of cells and tissues.

The lessons learned from the three articles lead Drs. Fuller and Insel to point out how this new policy will impact patient care.  The trend towards personalized medicine will mean that sex-related differences in cell physiology must be taken into consideration in the development of drugs and among patients.  For example, sex differences may be particularly important in stem cell-based therapies, with consideration given to the sex of both the donor and the recipient.

Drs. Fuller and Insel concede that it may be very difficult to fully understand the contribution of the sex to the function of cells.  However, the authors provide a fascinating overview of why this knowledge may make a difference to research outcomes and the way we understand health and disease, from the smallest cell to the largest human being.

NOTE TO EDITORS: The Editorial Focus by Drs. Fuller and Insel, “I don't know the question, but sex is definitely the answer! Focus on “In pursuit of scientific excellence: sex matters” and “Do you know the sex of your cells?”  is online at The editorial by Dr. Miller, “In pursuit of scientific excellence: sex matters,” is online at The Review article by Shah et al., “Do you know the sex of your cells?,” is online at For additional information contact

Physiology is the study of how molecules, cells, tissues and organs function in health and disease. Established in 1887, the American Physiological Society (APS) was the first U.S. society in the biomedical sciences field. The Society represents more than 10,500 members and publishes 15 peer-reviewed journals with a worldwide readership.