Digit ratio (2D:4D) and its relationship to foetal and maternal sex steroids: A mini-review

The challenges of terrestrial existence may mean that the early development of tetrapod limb traits is linked to the development of the urogenital system and sex steroids. One such limb trait is the sex-dependent ratio of the lengths of the 2nd and 4th digits (2D:4D). Direct evidence for the association between early sex steroids and offspring 2D:4D can be obtained by manipulating foetal sex hormones. However, this is not ethically permissible in humans. It is widely accepted that 2D:4D is a biomarker for early foetal sex hormones in tetrapods but the link in humans remains controversial. Here we review the evidence that (i) manipulation of sex steroids in early development leads to sex-dependent changes in 2D:4D throughout the tetrapods, and (ii) maternal sex steroids cross the placenta and thus are associated with offspring 2D:4D in both non-human and human animals. We suggest a research focus on associations between human maternal sex steroids and offspring 2D:4D to clarify the link between 2D:4D and early sex steroids. A protocol is proposed to examine the correlation between 1st-trimester maternal sex steroids and offspring 2D:4D. Such an association may explain the existence and medium effect size of the human sex difference in 2D:4D.