Testosterone treatment of pregnant rabbits affects sexual development of their daughters

Abstract The intrauterine position (IUP) may affect the sexual development of a female fetus in litter-bearing mammals. Females gestating between two males (2M) develop into masculinized adults compared to females without contiguous males (0M). Fetuses are known to secrete different types and amounts of steroid hormones during the prenatal period, and diffusing steroids may affect sexual differentiation of their neighbors, too. Exposure of elevated testosterone (T) levels generally results in masculinized anatomy and behavior in females of several rodent species. Our recent study showed that IUP-dependent masculinization is also present in the domestic rabbit, which shows large variation in sex related traits as adults. The aim of the present study was to test if the IUP effect in rabbits can be induced by exogenous testosterone treatment. By administering different doses of testosterone propionate (TP) to pregnant rabbits, and following anatomical and behavioral development of their female offspring, we obtained dose-dependent increase both in the anogenital distance (AGD) and chin-marking behavior of prenatal T exposed females. The effects of treatment corresponded to the variation due to intrauterine position in our previous study, namely, exposure to T of known external origin resulted in similar tendencies of masculinization in rabbit females as the in utero proximity to male siblings. Our results suggest that the IUP effects may have similar physiological bases across different mammalian taxa including Lagomorphs.