Lack of interaction between prenatal stress and prenatal letrozole to induce same-sex preference in male rats

Abstract

Same-sex partner preference between males has been observed in all species in which this behavior has been studied. Disruption of brain estradiol synthesis during development has been proposed as one of the biological causes underlying this behavior in some mammals. In support of this possibility, perinatal administration of aromatase inhibitors (such as letrozole) to male rat pups, induces around half of them to have same-sex preference and female sexual behavior in adulthood. Another putative factor that modifies sex preference is prenatal stress. Several stress protocols, applied to the pregnant dam, cause some of the adult male progeny to have an increased male preference, a decreased preference for the female, and lordosis behavior. Interestingly, these effects of stress might be mediated by its inhibitory action on brain aromatase. The aim of the present study was to analyze a possible interaction between these two factors in male rats. Pregnant dams were exposed to one of the four treatments across gestation days 10-22 (G10-G22): 1) vehicle-treated non-stressed controls; 2) letrozole (0.56 µg/kg); 3) 30 min immobilization stress); 4) both letrozole and stress combined. The male offspring were tested in adulthood for partner preference in a three-chambered arena, where we also recorded the masculine and feminine sexual behaviors. One week later males were tested for masculine and feminine sexual behavior in cylindrical arenas where they interacted for 30 min with a receptive female and thereafter with a sexually active male for another 30 min. Letrozole, stress and their combination resulted in same-sex preference in 40, 31 and 50% of males, respectively, compared to 5% in the control group. In the sexual behavior tests, prenatal stress reduced the percentage of males displaying intromissions and ejaculation (impaired masculinization), while letrozole mainly increased lordosis (impaired defeminization). The males prenatally submitted to stress and treated with letrozole presented these behavioral features but did not differ from both treatments given independently. The results indicate that the changes induced by stress or the aromatase inhibition produced by letrozole only accounts for a shift in partner preference in around half of the males and that there was no interaction between these two factors.

Keywords: Aromatase; Letrozole; Partner preference; Prenatal stress; Rat sexual behavior; Same-sex.