Early-to-Mid Gestation Fetal Testosterone Increases Right Hand 2D∶4D Finger Length Ratio in Polycystic Ovary Syndrome-Like Monkeys

A smaller length ratio for the second relative to the fourth finger (2D:4D) is repeatedly associated with fetal male-typical testosterone (T) and is implicated as a biomarker for a variety of traits and susceptibility to a number of diseases, but no experimental human studies have been performed. The present study utilizes the rhesus monkey, a close relative of humans, and employs discrete gestational exposure of female monkeys to fetal male-typical T levels for 15-35 days during early-to-mid (40-76 days; n = 7) or late (94-139 days; n = 7) gestation (term: 165 days) by daily subcutaneous injection of their dams with 10 mg T propionate. Such gestational exposures are known to enhance male-typical behavior. In this study, compared to control females (n = 19), only early-to-mid gestation T exposure virilizes female external genitalia while increasing 2D:4D ratio in the right hand (RH) by male-like elongation of RH2D. RH2D length and 2D:4D positively correlate with androgen-dependent anogenital distance (AG), and RH2D and AG positively correlate with duration of early-to-mid gestation T exposure. Male monkeys (n = 9) exhibit a sexually dimorphic 2D:4D in the right foot, but this trait is not emulated by early-to-mid or late gestation T exposed females. X-ray determined phalanx measurements indicate elongated finger and toe phalanx length in males, but no other phalanx-related differences. Discrete T exposure during early-to-mid gestation in female rhesus monkeys thus appears to increase RH2D:4D through right-side biased, non-skeletal tissue growth. As variation in timing and duration of gestational T exposure alter male-like dimensions of RH2D independently of RH4D, postnatal RH2D:4D provides a complex biomarker for fetal T exposure.