Environmental levels of oestrogenic and antiandrogenic compounds feminize digit ratios in male rats and their unexposed male progeny

Abstract

Digit length ratios, especially the second-to-fourth digit ratio (2D : 4D), are associated with various pathological and behavioural conditions in many species including humans and are dependent upon prenatal androgen to oestrogen balance. It is unknown whether digit ratios are modified by environmental exposure to ubiquitous endocrine disruptors. We studied the effect on adult male Wistar rat digit ratios of a gestational exposure to the oestrogenic and antiandrogenic compounds bisphenol A (BPA), genistein and vinclozolin, in low doses, and in combination with investigating in parallel a possible sexual dimorphism of this trait. We also investigated the effects on the male progeny not exposed during gestation. X-rays were taken of the left and right forepaws, and 2D-5D proximal to distal phalanx distances were measured by a standardized procedure based on semi-automatic image analysis. We provide evidence that there is a sexual dimorphism of digit ratios in the Wistar rat, and we found that BPA alone or in combination with genistein and vinclozolin significantly feminized digit ratios in male rats. Intriguingly, significant feminization of digit ratios was also found in the unexposed male progeny of males that had been exposed to compound mixtures. In conclusion, prenatal environmental levels of endocrine-active substances permanently disrupt digit ratios. Digit ratio measurement in adults is thus a promising biomarker of prenatal exposure to low-dose endocrine disruptors in rodents, with potential implications for future studies in humans.

Exposure to PBB-153 and Digit Ratio

“…Our findings suggest exposure to PBB-153 in-utero is associated with a higher, more feminized digit ratio. This main finding supports the possible estrogenic or anti-androgenic properties of PBB-153, as suggested in previous studies [7,14,15,19,20]. Previous studies based on the F1 daughters of the PBB Registry have found earlier pubic hair development and earlier menarche [21], and a dose-related increase in the risk of spontaneous abortion [22].…”

“…While an association between 2D:4D ratio and early life hormone levels has been observed in animals and humans [4,19], this is the first human study of 2D:4D ratio associated with in utero exposure to an environmental chemical capable of disrupting the endocrine system. Our findings regarding the timing of exposure (in-utero vs. current levels of PBB-153) supports the critical window of exposure in which development can be affected.…”

Adult digit ratio (2D:4D) is not related to umbilical cord androgen or estrogen concentrations, their ratios or net bioactivity

“…In male mice androgen antagonism or estrogen treatment in utero decreased the length of the fourth digit, but did not affect the second digit, creating a more female like digit ratio pattern [57]. Further, Auger et al [3] found the exposure to low (i.e. environmental) levels of estrogenic and anti-androgenic endocrine disruptors in utero feminised digit ratios in male rats.…”

Digit ratio (2D:4D) and physical fitness (Eurofit test battery) in school children

“…However, there may also be an influence on aerobic fitness via the developing foetus from the increasing use of endocrine distorters. Auger et al [50] have shown that environmental levels of commonly used oestrogenic and anti-androgenic compounds feminize 2D:4D in male rats. Interestingly, this effect is long-lasting and has epigenetic consequences, as it is carried on in the unexposed male progeny.…”