Considering sex as a biological variable in preclinical research

Miller, Leah; Marks, Carolyn; Becker, Jill B.; Hurn, Patricia D.; Chen, Wei Jung; Woodruff, Teresa K.; McCarthy, Margaret M.; Sohrabji, Farida; Schiebinger, Londa; Wetherington, Cora Lee; Makris, Susan L.; Arnold, Arthur P.; Einstein, Gillian; Miller, Virginia M.; Sandberg, Kathryn; Maier, Susan; Cornelison, Terri L.; Clayton, Janine Austin

doi:10.1096/fj.201600781r

Cited by 285 publications

(189 citation statements)

References 19 publications

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“…Over the years, male animals have been disproportionately studied in basic science research, leading to a lack of awareness of sex-specific differences (31, 32). Therefore, we included equally robust numbers of both male and female animals in our study.…”

Section: Resultsmentioning

confidence: 99%

(−)-P7C3-S243 Protects a Rat Model of Alzheimer’s Disease From Neuropsychiatric Deficits and Neurodegeneration Without Altering Amyloid Deposition or Reactive Glia

Voorhees

Remy

Cintrón-Pérez

et al. 2018

Biological Psychiatry

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Section: Resultsmentioning

confidence: 99%

(−)-P7C3-S243 Protects a Rat Model of Alzheimer’s Disease From Neuropsychiatric Deficits and Neurodegeneration Without Altering Amyloid Deposition or Reactive Glia

Voorhees

Remy

Cintrón-Pérez

et al. 2018

Biological Psychiatry

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“…In research, a distinction is made between sex as “sex,” meaning the chromosomal distribution in cells, and as “gender,” the gender determination provided for by society 7,8. Both categories are at the same time important preconditions for the way of life and pursuit of a person.…”

Section: Discussionmentioning

confidence: 99%

Infection control perception and behavior: a question of sex and gender? Results of the AHOI feasibility study

Goerig¹,

Dittmann²,

Krämer³

et al. 2018

IDR

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PurposeInfections, in particular with multidrug-resistant organisms, are a burden for inpatient and outpatient care and the whole community. The pathogens “roam” with patients and their relatives, forming an epidemiological bridge between different care facilities. Patients could play an important role in infection control, given that they are properly involved. The AHOI project stands for the Activation of patients, people in need of care, and care-providers for a Hygiene-conscious participatiOn in Infection prevention. To this end, a multimodal intervention bundle was developed and subjected to a feasibility study at a university hospital. Our goal was to clarify whether sex- and gender-specific characteristics are relevant in the field of infection prevention.Materials and methodsAHOI was tested with a cross-sectional design and a cross-media communication strategy at two surgical wards of a university hospital. Interventions included patient information brochures and motivational materials, reminders, and two video presentations. A welcome box with information material and two questionnaires was given to every inpatient. The patients were instructed to complete the questionnaires at the beginning and at the end of their stay.ResultsA sample size of 133 inpatients who completed questionnaires at the beginning and end of hospitalization was analyzable. The analysis produced a differentiated picture of the perception and reaction behavior of the sexes. Women had a more negative expectation of the response of doctors. In addition, there were differences in the perception of the positioning of disinfectant dispensers and cleaning processes as well as in satisfaction with the general cleanliness. For all subjects mentioned above, the differences were significant at least at the P-value 0.05.ConclusionThe AHOI study shows sex differences in hygiene perception and behavior. Measures to improve patient safety by involving patients in infection control must take these differences into account.

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“…However, several studies have addressed the possible role of gender as a biological variable–for example, lung and kidney injury, gut microbiota composition, haematopoiesis etc. [61–65]. Therefore, the gender-specific differences, along with organ- and species-specific differences, also deserve a careful consideration.…”

Section: Discussionmentioning

confidence: 99%

Regulated necrosis-related molecule mRNA expression in humans and mice and in murine acute tissue injury and systemic autoimmunity leading to progressive organ damage, and progressive fibrosis

et al. 2016

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The species-specific, as well as organ-specific expression of regulated necrosis (RN)-related molecules, is not known. We determined the expression levels of tumour necrosis factor receptor-1 (TNFR1), receptor activated protein kinase (RIPK)1, RIPK3, mixed lineage kinase domain-like (MLKL), CASP8, Fas-associated protein with death domain (FADD), cellular inhibitor of apoptosis protein (CIAP)1, CIAP2, glutathione peroxidase-4 (GPX4), cyclophilin D (CYPD), CASP1, NLRP3 and poly(ADP-ribose) polymerase-1 (PARP1) in human and mouse solid organs. We observed significant differences in expression of these molecules between human and mice. In addition, we characterized their expression profiles in acute as well as persistent tissue injury and chronic tissue remodelling using acute and chronic kidney injury models. We observed that the degree and pattern of induction of RN-related molecules were highly dependent on the trigger and disease pathogenesis. Furthermore, we studied their expression patterns in mice with lupus-like systemic autoimmunity, which revealed that the expression of MLKL, GPX4 and PARP1 significantly increased in the spleen along disease progression and CASP1, RIPK1, RIPK3 and CYPD were higher at the earlier stages but were significantly decreased in the later stages. In contrast, in the kidney, the expression of genes involved in pyroptosis, e.g. NLRP3 and CASP1 were significantly increased and TNFR1, RIPK1, RIPK3, CIAP1/2 and GPX4 were significantly decreased along the progression of lupus nephritis (LN). Thus, the organ- and species-specific expression of RN-related molecules should be considered during designing experiments, interpreting the results as well as extrapolating the conclusions from one species or organ to another species or organ respectively.

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Considering sex as a biological variable in preclinical research

Cited by 285 publications

References 19 publications

(−)-P7C3-S243 Protects a Rat Model of Alzheimer’s Disease From Neuropsychiatric Deficits and Neurodegeneration Without Altering Amyloid Deposition or Reactive Glia

(−)-P7C3-S243 Protects a Rat Model of Alzheimer’s Disease From Neuropsychiatric Deficits and Neurodegeneration Without Altering Amyloid Deposition or Reactive Glia

Infection control perception and behavior: a question of sex and gender? Results of the AHOI feasibility study

Regulated necrosis-related molecule mRNA expression in humans and mice and in murine acute tissue injury and systemic autoimmunity leading to progressive organ damage, and progressive fibrosis

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