Practical solutions for including Sex As a Biological Variable (SABV) in preclinical neuropsychopharmacological research

Dalla, Christina, Jaric, Ivana, Pavlidi, Pavlina, Hodes, Georgia E, Kokras, Nikolaos, Bespalov, Anton, Kas, Martien J, Steckler, Thomas, Kabbaj, Mohamed, Würbel, Hanno, Marroco, Jordan, Tollkuhn, Jessica, Shansky, Rebecca, Bangasser, Debra, Becker, Jill B, McCarthy, Margaret, Ferland-Beckham, Chantelle (October 2023) Practical solutions for including Sex As a Biological Variable (SABV) in preclinical neuropsychopharmacological research. Journal of Neuroscience Methods. p. 110003. ISSN 0165-0270

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DOI: 10.1016/j.jneumeth.2023.110003


Recently, many funding agencies have released guidelines on the importance of considering sex as a biological variable (SABV) as an experimental factor, aiming to address sex differences and avoid possible sex biases to enhance the reproducibility and translational relevance of preclinical research. In neuroscience and pharmacology, the female sex is often omitted from experimental designs, with researchers generalizing male-driven outcomes to both sexes, risking a biased or limited understanding of disease mechanisms and thus potentially ineffective therapeutics. Herein, we describe key methodological aspects that should be considered when sex is factored into in vitro and in vivo experiments and provide practical knowledge for researchers to incorporate SABV into preclinical research. Both age and sex significantly influence biological and behavioral processes due to critical changes at different timepoints of development for males and females and due to hormonal fluctuations across the rodent lifespan. We show that including both sexes does not require larger sample sizes, and even if sex is included as an independent variable in the study design, a moderate increase in sample size is sufficient. Moreover, the importance of tracking hormone levels in both sexes and the differentiation between sex differences and sex-related strategy in behaviors are explained. Finally, the lack of robust data on how biological sex influences the pharmacokinetic (PK), pharmacodynamic (PD), or toxicological effects of various preclinically administered drugs to animals due to the exclusion of female animals is discussed, and methodological strategies to enhance the rigor and translational relevance of preclinical research are proposed.

Item Type: Paper
Subjects: organism description > animal
organism description > animal behavior
organism description > animal > mammal
organism description > animal > mammal > rodent > mouse
neurobiology > neuroscience
organism description > animal > mammal > rodent
organism description > animal behavior > sex differences
neurobiology > neuroscience > systems neuroscience
CSHL Authors:
Communities: CSHL labs > Tollkuhn lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 31 October 2023
Date Deposited: 10 Nov 2023 14:11
Last Modified: 11 Apr 2024 13:58
PMCID: PMC10842858
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