Prenatal letrozole produces a subpopulation of male rats with same-sex preference and arousal as well as female sexual behavior

- Prenatal letrozole produces same-sex partner preference.
- Males with same-sex preference displayed normal sexual behavior with receptive female.
- Some males with same-sex preference displayed proceptivity and lordosis.
- No change in serum levels of sex steroids and gonadotropins was found.

Disruption of the sexual differentiation process during critical periods in male rodents produces changes in partner preference and sexual behavior. In this study we used prenatal (gestation days 10-22) letrozole (0.31 and 0.56 μg/kg) to inhibit aromatase and alter normal sexual differentiation of males. These animals and control rats (injected with vehicle) were used when adults to study: a) sexual preference (where the experimental male could choose to interact with a receptive female or a sexually experienced male); b) masculine and feminine sexual behaviors (tested in cylindrical arenas); c) non-contact erections when exposed to a female or a male and, d) serum sex steroids and gonadotropin levels. The results showed that 30% of the males treated with letrozole (0.56 μg/kg) had same-sex preference, 33% displayed lordosis and 63% showed non-contact erections in the presence of a sexually experienced male. However, 44% of these males also exhibited complete masculine sexual behavior towards receptive females. None of the control males displayed lordosis when mounted by another male and very few (12%) showed non-contact erections when exposed to a sexually experienced male. Similar low percentages were found in those males prenatally treated with the low letrozole dose (0.31 μg/kg). No difference was found in the serum levels of testosterone, estradiol, LH and FSH between control and letrozole-treated males regardless of their sexual preference. These results indicate that prenatal selective inhibition of aromatization produces feminization of sexual partner preference, arousal and sexual behavior but does not affect masculine sexual behavior.