Intrauterine Position Effects on Anogenital Distance and Digit Ratio in Male and Female Mice
- 337 Downloads
Anogenital distance (AGD) and the ratio of the second (index) to fourth (ring) digit lengths (2D:4D) are two widely used indicators of prenatal androgen exposure. The former is commonly used in rodent models, while the latter is principally used in human studies. We investigated variation in these two traits in C57BL/6J mice to test the hypothesis that variation in these two traits reflect a common underlying variable, presumably testosterone exposure. AGD is a sexually dimorphic trait used to sex young rodents. This distance typically increases and becomes more male-like in females pups when their uterine neighbors are male. 2D:4D is sexually dimorphic in a number of species, including humans and other great apes. Lower digit ratios may be associated with greater exposure to androgens during fetal development in humans. We found the expected sexual dimorphism in AGD, but no significant sex difference in 2D:4D, and no correlation between 2D:4D and AGD. Gestating next to males increased a pup’s 2D:4D ratio, but it had no effect on AGD. The lack of correlation between 2D:4D and AGDs in this mouse strain suggests that these two measures do not reflect a common influence of androgen exposure. The possible roles of temporal and localized effects of masculinization are discussed.
KeywordsIntrauterine position Digit ratio 2D:4D Anogenital distance Masculinization
Research funding by NSERC (Canada) Discovery Grant (249685) to PLH. AGDs were measured by AAB and RHY, 2D:4D by PAG and RHY, and Cesarean sections and gonadal inspections were performed by SP. We wish to thank Doug Wong-Wylie for graciously lending his stereoscope and camera, and Janelle Pakan for assistance in collecting the data. Thanks to John Manning, Dennis McFadden, and Norm Stacey for valuable discussion and comments on this manuscript, and to Clay Dickson, Andy Iwaniuk, Jodie Jawor, Jim Martin, Steve Phelps, Doug Wahlsten, and Karen Wendt for comments on earlier versions.
- Clark, M. M., Robertson, R. K., & Galef, B. G. J. (1996). Effects of perinatal testosterone on handedness in gerbils: Support for part of the Geschwind-Galaburda hypothesis. Behavioral Neuroscience, 110, 1–5.Google Scholar
- Efron, B., & Tibshirani, R. J. (1994). Introduction to the bootstrap. New York: Chapman & Hall.Google Scholar
- Hines, M., Fane, B. A., Pasterski, V. L., Mathews, G. A., Conway, G. S., & Brook, C. (2002). Spatial abilities following prenatal androgen abnormality: Targeting and mental rotations performance in individuals with congenital adrenal hyperplasia. Psychoenuroendocrinology, 28, 1010–1026.CrossRefGoogle Scholar
- Kaufman, M. H. (1994). Atlas of mouse development. London: Academic Press.Google Scholar
- Manning, J. T. (2002). Digit ratio: A pointer to fertility, behavior, and health. New Brunswick, NJ: Rutgers University Press.Google Scholar
- Manning, J. T., Barley, L., Walton, J., Lewis-Jones, D., Trivers, R. L., Singh, D., et al. (2000). The 2nd:4th digit ratio, sexual dimorphism, population differences, and reproductive success: Evidence for sexually antagonistic genes. Evolution and Human Behavior, 21, 163–183.PubMedCrossRefGoogle Scholar
- Manoli, I., Kanaka-Gantenbein, C., Voutetakis, A., Maniati-Christidi, M., & Dacou-Voutetakis, C. (2002). Early growth, pubertal development, body mass index and final height of patients with congenital adrenal hyperplasia: Factors influencing the outcome. Clinical Endocrinology, 57, 669–676.PubMedCrossRefGoogle Scholar
- Naftolin, F., & MacLusky, N. (1984). Aromatization hypothesis revisited. In M. Serio, M. Motta, M. Zanisi, & L. Marini (Eds.), Sexual differentiation: Basic and clinical aspects (Vol. 11, pp. 79–91). New York: Raven Press.Google Scholar
- R Development Core Team. (2004). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria.Google Scholar
- Saino, N., Rubolini, D., Romano, M., & Boncoraglio, G. (2007). Increased egg estradiol concentration feminizes digit ratios of male pheasants (Phasianus colchicus). Naturwissenschaften, doi: 10.1007/s00114-006-0188-9.
- vom Saal, F. (1984). The intrauterine position phenomenon: Effects on physiology, aggressive behavior and population dynamics in house mice. In K. Flannelly, R. Blanchard, & D. Blanchard (Eds.), Biological perspectives on aggression (pp. 135–179). New York: Alan R. Liss.Google Scholar
- vom Saal, F. S. (1989). Sexual differentiation in litter bearing animals: Influence of sex of adjacent fetuses in utero. Journal of Animal Sciences, 67, 1824–840.Google Scholar
- vom Saal, F. S., Timms, B. G., Montano, M. M., Planza, P., Thayer, K. A., & Thayer, K. A. (1997). Prostate enlargement in mice due to fetal exposure to low doses of estradiol or diethylstilbestrol and opposite at high doses. Proceedings of the National Academy of Sciences of the United States of America, 94, 2056–2061.PubMedCrossRefGoogle Scholar
- Williams, T. J., Pepitone, M. E., Christensen, S. E., Cooke, B. M., Huberman, A. D., Breedlove, N. J., et al. (2000). Finger-length ratios and sexual orientation. Nature, 404, 455–456.Google Scholar
- Woodson, J. C., & Gorski, R. A. (1999). Structural sex differences in the mammalian brain: Reconsidering the male/female dichotomy. In A. Matsumoto (Ed.), Sexual differentiation of the brain (pp. 229–255). Boca Raton, FL: CRC Press.Google Scholar