Programming Effects of Antenatal Corticosteroids Exposure in Male Sexual Behavior Mário Oliveira, MD, Pedro Leão, MD, PhD, Ana-João Rodrigues, PhD, José-Miguel Pêgo, MD, PhD, João-José Cerqueira, MD, PhD, and Nuno Sousa, MD, PhD Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal DOI: 10.1111/j.1743-6109.2010.02170.x ABSTRACT Introduction. Brain regions implicated in sexual behavior begin to differentiate in the last trimester of gestation. Antenatal therapy with corticosteroids is often used in clinical practice during this period to accelerate lung maturation in preterm-risk pregnancies. Clinical and animal studies highlighted major behavioral impairments induced later in life by these treatments, especially when synthetic corticosteroids are used. Aim. To evaluate the implications of acute prenatal treatment with natural vs. synthetic corticosteroids on adult male rat sexual behavior and its neurochemical correlates. Methods. Twelve pregnant Wistar rats were injected with dexamethasone (DEX—1 mg/kg), corticosterone (CORT—25 mg/kg), or saline on late gestation (pregnancy days 18 and 19). Following this brief exposure to corticosteroids, we assessed the sexual behavior of the adult male progeny and subsequently associated these behaviors with the levels of catecholamines and mRNA of dopamine and androgen receptors (AR) in brain regions relevant for sexual behavior. Main Outcome Measures. Sexual behavior of adult male offspring was assessed by exposure to receptive females. This was associated with serum testosterone levels and levels of catecholamines (determined by high-performance liquid chromatography) and dopamine and AR mRNA expression (real-time polymerase chain reaction [PCR]) in brain regions implicated in sexual behavior. Results. Prenatal DEX exposure resulted in a decreased number and increased mounts and intromissions latencies in adulthood. These findings were associated with decreased levels of serum testosterone and increased hypothalamic expression of AR mRNA. DEX animals also displayed lower dopamine levels and higher dopamine receptor mRNA expression both in hypothalamus and nucleus accumbens (NAcc). The milder phenotype of CORT animals was associated only with decreased dopamine levels in NAcc. Conclusion. Antenatal corticotherapy programs adult male sexual behavior through changes in specific neuronal and endocrine mediators. Importantly, equipotent doses of CORT trigger less detrimental consequences than DEX, emphasizing the differential impact of activation of the different corticosteroid receptors. Oliveira M, Leão P, Rodrigues A-J, Pêgo J-M, Cerqueira J-J, and Sousa N. Programming effects of antenatal corticosteroids exposure in male sexual behavior. J Sex Med 2011;8:1965–1974. Key Words. Antenatal Corticotherapy; Corticosteroids; Dopamine; Neurodevelopment; Sexual Behavior; Central Neurochemichal Correlates Introduction T he last trimester of gestation and early post- natal period are critical for brain sexual dif- ferentiation [1]. Insults at this period, including stress and prolonged exposure to corticosteroids, have been shown to disrupt several behaviors in adulthood, namely male sexual behavior [2–4]. Interestingly, exposure to corticosteroids during late gestation has been correlated with a sustained perturbation in male steroidogenesis [5] and an impoverished dopaminergic innervation of the nucleus accumbens (NAcc) [6], which is of particu- lar relevance when considering the facilitatory role 1965 © 2011 International Society for Sexual Medicine J Sex Med 2011;8:1965–1974 Downloaded from https://academic.oup.com/jsm/article/8/7/1965/6980077 by guest on 25 January 2023