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Overexpression of Androgen Receptors Masculinizes 2D:4D Digit Ratios in Mice

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Abstract

Studying the role of the prenatal endocrine environment in humans is challenging due to the ethical and practical considerations of measuring hormone levels of the develo** fetus. Because it has been difficult to ascertain whether prenatal androgens contribute to the brain and behavior in humans as it does in non-human species, retrospective markers of prenatal androgens, such as the second-to-fourth finger digit ratio (2D:4D), are of interest to the studying of human behavioral endocrinology. To assess the validity of such markers, laboratory animals have been studied. Some strains of mice have been reported to show a sex difference in 2D:4D, and pharmacological and genetic manipulation of the androgen and estrogen receptors (AR and ER) has implicated a role for prenatal androgens in mediating this sex difference, although there have been conflicting reports. Here, we compared mice with global AR overexpression to mice with wildtype (WT) littermates and mice with neural-specific AR overexpression. We found a sex difference in the right hind paw, such that males had larger digit ratios than females. Regardless of sex, mice with global AR overexpression showed an increase in the right hind 2D:4D ratio compared with both WT and neural-specific AR overexpression mice. These results support a role for non-neural AR in the development of 2D:4D and suggest that increased sensitivity to androgens via increased AR is sufficient to increase the masculinization of digit ratios. Future directions for confirming the validity of 2D:4D as a marker for prenatal androgen exposure are discussed.

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Acknowledgements

This research was supported by a doctoral Canada Graduate Scholarship from the Natural Sciences and Engineering Research Council of Canada (NSERC) to ASG and NSERC Discovery Grants to ASG and DAM.

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Authors and Affiliations

  1. Department of Psychology, Faculty of Science, Memorial University of Newfoundland, 232 Elizabeth Ave, St. John’s, NL, A1B 3X9, Canada

    Ashlyn Swift-Gallant

  2. Neuroscience Program, Michigan State University, East Lansing, MI, USA

    Victor Di Rita

  3. Department of Psychology, University of Toronto, Toronto, ON, Canada

    Lindsay A. Coome & D. Ashley Monks

  4. Department of Cells and Systems Biology, University of Toronto, Toronto, ON, Canada

    D. Ashley Monks

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  1. Ashlyn Swift-Gallant
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  2. Victor Di Rita
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  3. Lindsay A. Coome
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  4. D. Ashley Monks
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Correspondence to Ashlyn Swift-Gallant.

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Procedures adhered to Canadian Council on Animal Care Regulations and were approved by the Local Animal Care Committee at the University of Toronto, Mississauga.

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Swift-Gallant, A., Di Rita, V., Coome, L.A. et al. Overexpression of Androgen Receptors Masculinizes 2D:4D Digit Ratios in Mice. Arch Sex Behav 50, 3413–3417 (2021). https://doi.org/10.1007/s10508-021-02161-y

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  • DOI: https://doi.org/10.1007/s10508-021-02161-y

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