Measurement of the digit lengths and the anogenital distance in mice

Abstract

In humans, research has demonstrated the ratio of the 2nd to 4th digit lengths (2D:4D) are: (i) sexually dimorphic with males having a lower ratio than females, the latter having near equidistant lengths [J. Manning, D. Scutt, J. Wilson, & D. Lewis-Jones, (1998). The ratio of 2nd to 4th digit length: a predictor of sperm numbers and concentrations of testosterone, luteinizing hormone and oestrogen. Hum Reprod. 13(11):3000-3004], and are theorized to be (ii) determined in utero during gestational development [J. Manning, & P. Bundred, (2000). The ratio of 2nd to 4th digit length: a new predictor of disease predisposition? Med Hypotheses. 54(5):855-857], and (iii) correlated with prenatal androgen levels [J. Manning, & P. Bundred, (2000). The ratio of 2nd to 4th digit length: a new predictor of disease predisposition? Med Hypotheses. 54(5):855-857; J. Manning, R. Trivers, D. Singh, & R. Thornhill, (1999). The mystery of female beauty. Nature. 399:214-215; T. Williams, M. Pepitone, S. Christensen, B. Cooke, A. Huberman, N. Breedlove, et al., (2000). Finger-length ratios and sexual orientation: measuring people's finger patterns may reveal some surprising information. Nature. 404:455-456]. These phenotypes correspond to the hormonal effects of testosterone (i.e. androgens) in utero in both sexes. In mice, testosterone in utero is associated in males and females with the anogenital distance (AGD), a phenotype where AGD is greater in males and females contiguous with two males (2M) have a masculinized AGD phenotype whereas those juxtaposed to fewer males, one or zero (1M or 0M), have a more feminine phenotype, i.e. shorter AGD [F. vom Saal, & F. Bronson, (1980). Sexual characteristics of adult female mice are correlated with their blood testosterone levels during prenatal development. Science. 208:597-599; R. Gandelman, F. vom Saal, & J. Reinisch, (1977). Contiguity to male foetuses affects morphology and behaviour of female mice. Nature. 266:722-724; A. Hotchkiss, & J. Vandenbergh, (2005). The anogenital distance index of mice (Mus musculus domesticus): an analysis. Contem Top Lab Anim Sci. 44(4):46-48; C. Kinsley, J. Miele, C. Wagner, L. Ghiraldi, J. Broida, B. Svare, (1986). Prior intrauterine position influences body weight in male and female mice. Horm Behav. 20:201-211; S. Graham, R. Gandelman, (1986). The expression of ano-genital distance data in the mouse. Physiol Behav. 36(1):103-104; B. Ryan, & J. Vandenbergh, (2002). Intrauterine position effects. Neurosci Biobehav Rev. 26(6):665-678; J. Vandenbergh, & C. Huggett, (1995). The anogenital distance index, a predictor of the intrauterine position effects on reproduction in female house mice. Lab Anim Sci. 45(5):567-573]. Furthermore, in humans AGD is sexually dimorphic with neonate males having a greater distance than females [E. Salazar-Martinez, P. Romano-Riquer, E. Yanez-Marquez, M. Longnecker, M. Hernandez-Avila, (2004). Anogenital distance in human male and female newborns: a descriptive, cross-sectional study. Environmental Health: A Global Access Science Source. 2004:3:(8) (doi:10.1186/1476-069X-3-8) [12]]. Recently, research has concluded that the digit lengths of mice have the same phenotypic pattern seen in humans, with the 2D:4D ratio being sexually dimorphic, i.e. lower in males and greater in females [W. Brown, C. Finn, & S. Breedlove, (2002). Sexual dimorphism in digit-length ratios of laboratory mice. Anat Rec. 267(3):231-234; J. Manning, M. Callow, & P. Bundred, (2003). Finger and toe ratios in humans and mice: implications for the aetiology of diseases influenced by HOX genes. Med Hypotheses. 60(3):340-343; W. Brown, C. Finn, & S. Breedlove, (2001). A sex difference in the digit length ratio in mice. Horm Behav. 39:325]. The following study was conducted to determine whether the digit length ratios in mice are correlated with a known in utero testosterone-dependent effect, the distance from the anus to the genital papilla, the AGD. The results of the experiment demonstrate that there is no correlation between AGD and the 2D:4D ratio in mice of either sex. Furthermore, no sexual dimorphism in the digit lengths was found as opposed to previous studies [W. Brown, C. Finn, & S. Breedlove, (2002). Sexual dimorphism in digit-length ratios of laboratory mice. Anat Rec. 267(3):231-234; J. Manning, M. Callow, & P. Bundred, (2003). Finger and toe ratios in humans and mice: implications for the aetiology of diseases influenced by HOX genes. Med Hypotheses. 60(3):340-343; W. Brown, C. Finn, & S. Breedlove, (2001). A sex difference in the digit length ratio in mice. Horm Behav. 39:325]. Although testosterone has been implicated in the digit length ratios, the present study would suggest that androgens do not have a causal relationship with testosterone-dependent phenotypes [J. Manning, D. Scutt, J. Wilson, & D. Lewis-Jones, (1998). The ratio of 2nd to 4th digit length: a predictor of sperm numbers and concentrations of testosterone, luteinizing hormone and oestrogen. Hum Reprod. 13(11):3000-3004; J. Manning, & P. Bundred, (2000). The ratio of 2nd to 4th digit length: A new predictor of disease predisposition?. Med Hypotheses. 54(5):855-857; J. Manning, R. Trivers, D. Singh, & R. Thornhill, (1999). The mystery of female beauty. Nature. 399:214-215]. The attribution of nature (i.e. genetic) and nurture (i.e. environment) in the development of life (i.e. resultant phenotype) is exceedingly complex and the correlation of one trait to another physical characteristic does not preclude there is a causal relationship.