Breaking the Cycle: Estrous Variation Does Not Require Increased Sample Size in the Study of Female Rats.
Despite the striking differences between male and female physiology, female physiology is understudied. In response, the National Institutes of Health is promulgating new policies to increase the use of female organisms in preclinical research. Females are commonly believed to have greater variability than males because of the estrous cycle, but recent studies call this belief into question. Effects of estrous cycling on mean arterial pressure were assessed in female Dahl S rats using telemetry and vaginal cytometry and found that estrous cycling did not affect mean arterial pressure magnitude or variance. Data from the PhysGen arm of the Program for Genomic Applications was used to compare male and female variance and coefficient of variation in 142 heart, lung, vascular, kidney, and blood phenotypes, each measured in hundreds to thousands of individual rats from over 50 inbred strains. Seventy-four of 142 phenotypes from this data set demonstrated a sex difference in variance; however, 59% of these phenotypes exhibited greater variance in male rats rather than female. Remarkably, a retrospective power analysis demonstrated that only 16 of 74 differentially variable phenotypes would be detected when using an experimental cohort large enough to detect a difference in magnitude. No overall difference in coefficient of variation between male and female rats was detected when analyzing these 142 phenotypes. We conclude that variability of 142 traits in male and female rats is similar, suggesting that differential treatment of males and females for the purposes of experimental design is unnecessary until proven otherwise, rather than the other way around.
From the Department of Physiology (A.D., E.C.E., J.D.B., T.J.S., T.K., M.S., A.S.G., A.W.C.) and Department of Biomedical Engineering (A.S.G.), Medical College of Wisconsin, Milwaukee.
Alex
A
Dayton
From the Department of Physiology (A.D., E.C.E., J.D.B., T.J.S., T.K., M.S., A.S.G., A.W.C.) and Department of Biomedical Engineering (A.S.G.), Medical College of Wisconsin, Milwaukee.
Eric C
EC
Exner
From the Department of Physiology (A.D., E.C.E., J.D.B., T.J.S., T.K., M.S., A.S.G., A.W.C.) and Department of Biomedical Engineering (A.S.G.), Medical College of Wisconsin, Milwaukee.
John D
JD
Bukowy
From the Department of Physiology (A.D., E.C.E., J.D.B., T.J.S., T.K., M.S., A.S.G., A.W.C.) and Department of Biomedical Engineering (A.S.G.), Medical College of Wisconsin, Milwaukee.
Timothy J
TJ
Stodola
From the Department of Physiology (A.D., E.C.E., J.D.B., T.J.S., T.K., M.S., A.S.G., A.W.C.) and Department of Biomedical Engineering (A.S.G.), Medical College of Wisconsin, Milwaukee.
Theresa
T
Kurth
From the Department of Physiology (A.D., E.C.E., J.D.B., T.J.S., T.K., M.S., A.S.G., A.W.C.) and Department of Biomedical Engineering (A.S.G.), Medical College of Wisconsin, Milwaukee.
Meredith
M
Skelton
From the Department of Physiology (A.D., E.C.E., J.D.B., T.J.S., T.K., M.S., A.S.G., A.W.C.) and Department of Biomedical Engineering (A.S.G.), Medical College of Wisconsin, Milwaukee.
Andrew S
AS
Greene
From the Department of Physiology (A.D., E.C.E., J.D.B., T.J.S., T.K., M.S., A.S.G., A.W.C.) and Department of Biomedical Engineering (A.S.G.), Medical College of Wisconsin, Milwaukee. cowley@mcw.edu.
Allen W
AW
Cowley
D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D003345:Corticosterone / Q000097:blood; D030762:Estrous Cycle / Q000235:genetics / Q000502:physiology*; D005260:Female; D008297:Male; D023421:Models, Animal; D010641:Phenotype; D051381:Rats; D020303:Rats, Inbred Dahl; D018401:Sample Size; D012680:Sensitivity and Specificity; D012727:Sex Characteristics
D003345:Corticosterone
estrous cycle; experimental design; experimental models; sample size; sex; variation
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