Sex Reporting in Preclinical Microbiological and Immunological Research

Abstract

Both sex (i.e., biological construct of male and female) and gender (i.e., social construct of masculine and feminine) impact the pathogenesis of diseases, including those caused by microbial infections. Following the 2015 NIH policy for consideration of sex as a biological variable in preclinical research, in 2018, authors of papers published in primary-research American Society for Microbiology (ASM) journals will be asked to report the sex of the research subjects and animals and of materials derived directly from them. To address the need for sex reporting in ASM journals, we systematically reviewed 2,928 primary-research articles published in six primary-research ASM journals (Antimicrobial Agents and Chemotherapy, Clinical and Vaccine Immunology, Infection and Immunity, Journal of Bacteriology, Journal of Virology, and mBio) in 2016. Approximately 37% of animal studies and 9% of primary cell culture papers published in 2016 would have been affected by the new sex-reporting policy. For animal studies (i.e., studies with any nonhuman vertebrate hosts), most published papers either did not report the sex of the animals or used only female animals, and a minority used only males or both sexes. For published studies using primary cells from diverse animal species (i.e., humans and nonhuman vertebrates), almost all studies failed to report the sex of donors from which the cells were isolated. We believe that reporting the sex of animals and even of the donors of derived cells could improve the rigor and reproducibility of research conducted in microbiology and immunology and published in ASM journals.

Keywords: immunology; microbiology; sex reporting.

FIG 1

The number of published papers listed in PubMed pertaining to sex differences in microbiology and immunology. On 26 September 2017, PubMed search results for “sex differences” and “microbiology” yielded a total of 4,456 papers published between 1960 and 2017 (A) and search results for “sex differences” and “immunology” yielded a total of 7,086 papers that were published between 1957 and 2017 (B). For each search, there was an increase (i.e., >100 papers/year) in the 1990s. Since the 1990s, there has been a steady increase in the number of published papers in microbiology and immunology relevant to sex-difference research.

FIG 2

The proportion of papers published in 2016 in ASM journals that would be affected by a sex-reporting policy (A) and that report the sex of their animals (B) or primary cell cultures (C). The proportion of papers published in each of six ASM journals (i.e., Antimicrobial Agents and Chemotherapy, Clinical and Vaccine Immunology, Infection and Immunity, Journal of Bacteriology, Journal of Virology, and mBio) describing nonhuman animal research or the use of primary cell cultures from either humans (e.g., peripheral blood mononuclear cells stimulated and tested in vitro) or nonhuman animals (e.g., bone marrow-derived cells differentiated, stimulated, and tested in vitro) was determined (A) and then evaluated for whether the papers reported the sex of their animals (B) or the donors of their cells (C) and, if so, whether only males, only females, or both sexes were used. Numbers in parentheses represent the total number of papers in each category.