Male or female? Disease progress depends on the sex
The international research consortium IMPC has shown that sex influences the prevalence, course and severity of the majority of common diseases and disorders. The German Mouse Clinic, Helmholtz Zentrum München, played an important role in this study, published in Nature Communications. The analyzed data illustrate the differences between male and female mice – known as sexual dimorphism - and the results have implications for the design of clinical studies.
Scientists often design research studies or toxicological examinations with male experimental animals, assuming that the results will have a standard validity. “In times of personalized medicine, it is obvious that differences between the sexes should also be taken into consideration. Susceptibility to disease, disease progression, and healing processes can be of fundamental difference in males and females,” says Prof. Dr. Martin Hrabě de Angelis, Director of the Institute of Experimental Genetics at the Helmholtz Zentrum München and Director of the German Mouse Clinic.
The IMPC has an invaluable amount of phenotyping data produced under exact standardized conditions, that allows for the first time a complex statistical analysis of sexual dimorphism between females and males. Altogether, data from wild type mice and genetically modified mice were compared.
This statistical evaluation was performed under the leadership of the Welcome Trust Sanger Institute; the data was provided by the IMPC centers including the German Mouse Clinic. The alterations found in the phenotypes and parameters of a number of organ systems can be predictors for differences in the prevalence of diseases, disease progress, and the effect of medications.
“In the future, this work can be the basis for an adapted design of animal studies and clinical studies,” explains Prof. Hrabě de Angelis. “Given what we know today, the transfer of scientific findings from one sex to the other is not meaningful any longer, and can even be dangerous with regard to later drug development.”
Karp NA, Mason J, Beaudet AL, Benjamini Y, Bower L, Braun RE, Brown SDM, Chesler EJ, Dickinson ME, Flenniken AM, Fuchs H, Angelis MH, Gao X, Guo S, Greenaway S, Heller R, Herault Y, Justice MJ, Kurbatova N, Lelliott CJ, Lloyd KCK, Mallon AM, Mank JE, Masuya H, McKerlie C, Meehan TF, Mott RF, Murray SA, Parkinson H, Ramirez-Solis R, Santos L, Seavitt JR, Smedley D, Sorg T, Speak AO, Steel KP, Svenson KL; International Mouse Phenotyping Consortium, Wakana S, West D, Wells S, Westerberg H, Yaacoby S, White JK. Prevalence of sexual dimorphism in mammalian phenotypic traits. Nat Commun. 2017 Jun 26;8:15475. doi: 10.1038/ncomms15475.