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Male or female sex: considerations and translational aspects in diabetic foot ulcer research using rodent models

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Abstract

Treatment of nonhealing diabetic foot ulcers (DFUs) is a major clinical concern and challenge for clinicians. Despite the advancement in treatment strategies, there is no definitive treatment for complicated nonhealing DFUs. Animal models are crucial for understanding pathogenesis and investigating novel therapeutic small molecules and the rodent model is commonly used for research related to cutaneous wound healing. Sexual dimorphism and its effect on the efficacy of sex hormones in enhancing healing in cutaneous wounds using a rodent model have been discussed, however, there is a lack of data related to diabetic foot ulcers. Further, the effects of sexual dimorphism on the issues related to induction of diabetes, differential immune response, type and size of the wound, the effectiveness of topical versus systemic treatment, and molecular mechanisms involved in wound healing like hemostasis, granulation tissue formation, the response of keratinocytes and fibroblasts, inflammation, and skin anatomy are scarcely discussed. Understanding these aspects is of significance and will help in choosing the correct sex, species, and strain of rodents while investigating therapeutic small molecules for DFUs. This review critically summarized these issues and their translational aspects followed by highlighting the effect of sexual dimorphism on these important aspects.

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Funding

VR is supported by an intramural grant IMR Rai 12397B from the Western University of Health Sciences, Pomona, California. The research work of DKA is supported by the R01 HL144125 and R01 HL147662 grants from the National Institutes of Health, USA. The content of this critical review is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Western University of Health Sciences,IMR Rai 12397B,National Institutes of Health,R01 HL144125,R01HL147662

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  1. Department of Translational Research, Western University of Health Sciences, 309 E. Second Street, Pomona, CA, 91766-1854, USA

    Vikrant Rai & Devendra K. Agrawal

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VR: conceptualized and wrote the initial draft, DKA: critically reviewed and edited the manuscript, VR and DKA: finalized the manuscript.

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Rai, V., Agrawal, D.K. Male or female sex: considerations and translational aspects in diabetic foot ulcer research using rodent models. Mol Cell Biochem 478, 1835–1845 (2023). https://doi.org/10.1007/s11010-022-04642-7

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