Endocrine Disruptors and Hypothalamic Sexual Differentiation

The so-called endocrine disruptors have been described as compounds which interfere with the estrogen action in their receptors and may exert a crucial role in the development of the reproductive tract and in the brain sexual differentiation. Thus, conducts and/or exposure to these drugs in the perinatal period that apparently do not endanger the neonate may cause side effects. During embrionary development, the gonads, through discharge of a small quantity of reproductive hormones, will guarantee the phenotype of male or female at birth, as well as actuate in specific areas sexual differentiation of the central nervous system. Several experimental models have shown an interference of drugs acting as endocrine disruptors in hypothalamic sexual differentiation. Thus, reproductive function is impaired by exposure to estrogen in the perinatal life of rats and the mechanisms involved in this effect are distinct for males and females. Perinatal exposure to drugs which may be considered endocrine disrupters may induce an incomplete masculinization and defeminization of the central nervous system. Alterations in these processes, if present, generally are perceived only at puberty or adult reproductive life. These later alterations may include anomalies in the process of fertility or in sexual behavior

Prenatal testosterone supplementation alters puberty onset, aggressive behavior, and partner preference in adult male rats

The objective of this study was to investigate whether prenatal exposure to testosterone (T) could change the body weight (BW), anogenital distance (AGD), anogenital distance index (AGDI), puberty onset, social behavior, fertility, sexual behavior, sexual preference, and T level of male rats in adulthood. To test this hypothesis, pregnant rats received either 1 mg/animal of T propionate diluted in 0.1 ml peanut oil or 0.1 ml peanut oil, as control, on the 17th, 18th and 19th gestational days. No alterations in BW, AGD, AGDI, fertility, and sexual behavior were observed (p > 0.05). Delayed onset of puberty (p 0.05), altered pattern of sexual preference (p < 0.05), and reduced T plasma level (p < 0.05) were observed for adult male rats exposed prenatally to T. In conclusion, the results showed that prenatal exposure to T was able to alter important aspects of sexual and social behavior although these animals were efficient at producing descendants. In this sense more studies should be carried to evaluated the real impact of this hormonal alteration on critical period of sexual differentiation on humans, because pregnant women exposed to hyperandrogenemia and then potentially exposing their unborn children to elevated androgen levels in the uterus can undergo alteration of normal levels of T during the sexual differentiation period, and, as a consequence, affect the reproductive and behavior patterns of their children in adulthood.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Reproductive changes in male rats treated perinatally with an aromatase inhibitor.

The effects of maternal exposure to aromatase inhibitor during the perinatal period of sexual brain differentiation were studied. The fertility was assessed in adult, male rat offspring of aromatase inhibitor-treated dams. The following results were obtained: (1) Sexual maturation, body weight, and wet weights of testis, pituitary, seminal vesicle, ventral prostate, and levatori ani muscle were unchanged at adult life. (2) Fifty percent of the animals were able to mate with normal females, which became pregnant but exhibited an increased number of preimplantation loss. (3) There was a decrease in the number of spermatozoa found in the testes and in the daily sperm production. (4) Of those, 25% of the male rats treated with aromatase inhibitor did not present male sexual behavior, showing female behavior when pretreated with estrogen. These results indicate that perinatal exposure to aromatase inhibitor during the critical period of male brain sexual differentiation has a long-term effect on the reproductive physiology and behavior of male rats

Adult partner preference and sexual behavior of male rats exposed prenatally to betamethasone

The aim of this Study was to investigate long-term effects of prenatal betamethasone exposure oil sexual partner preference, testosterone level, and sexual behavior. Pregnant rats received 0.1 mg/kg of betamethasone or saline on the 12th, 13th, 18th, and 19th days of pregnancy. Parameters in male offspring were evaluated at 90 days of age. Male rats from the betamethasone group did not show any difference in sexual partner preference as expressed by the total number of visits to the female or male zone. However, these males spent significantly less total time and shorter duration per visit in the female zone than their controls. Therefore, prenatal exposure to betamethasone led to a significantly lower sexual female partner preference score compared to the control group. These animals also presented diminished testosterone levels in adulthood. Prenatal exposure to betamethasone induced a delay in the latency to first ejaculation. as well as a decrease in the numbers of postejaculatory intromissions, total intromissions and total ejaculations. Although 80% of the betamethasone-treated animals exhibited male Sexual behavior, when they were castrated and pretreated with estrogen, 50% of them showed lordosis and accepted mounts of another sexually experienced male. These results suggest that the prenatal treatment with betamethasone, by increasing maternal corticosteroid level, may have diminished testosterone peak in male pups, a peak crucial to brain sexual differentiation. As a consequence, the prenatal betamethasone treatment reduced the testosterone level in adulthood and altered partner preference and Sexual behavior. (C) 2009 Elsevier B.V. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Effects of swimming and nandrolone decanoate treatment on vas deferens response to norepinephrine

Aims: To investigate the response to norepinephrine of vas deferens isolated from intact and castrated rats submitted to swimming and/or treated with nandrolone decanoate.Main methods: Intact and castrated male rats were submitted to swimming for 15 days, 1 session per day, 5 days/week and were either treated or not with 7.5 mg/kg of nandrolone decanoate on days 1, 5, 9, and 13 after the beginning of training. Plasma androgen concentration was measured by radioimmunoassay. Vas deferens was isolated and set up for analysis of its contractile capacity in response to norepinephrine.Key findings: In intact rats, nandrolone, training, and training plus nandrolone did not change body mass or vas deferens weight. In castrated rats, the vas deferens wet weight was decreased in both untrained and trained groups. In castrated rats, nandrolone prevented vas deferens atrophy. In intact animals, nandrolone decreased (P<0.05) the androgen level in untrained group, while in castrated rats this treatment partially restored the androgen level. An increased sensitivity (P<0.05) to norepinephrine was observed in vas deferens isolated from intact trained rats, treated or not with nandrolone decanoate, while nandrolone did not alter norepinephrine response in organs from untrained animals. In untrained castrated rats, nandrolone fully restored the sensitivity to norepinephrine in untrained rats, while in trained castrated rats the anabolic steroid only partially restored this response.Significance: The present results indicate that training can increase norepinephrine response of vas deferens in intact rats, while nandrolone decanoate can partially restore the responsiveness to norepinephrine in castrated rats. (C) 2009 Published by Elsevier B.V.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Effects of nandrolone decanoate and resistance exercise on skeletal muscle in adult male rats

The aim of this study was to compare the effects of resistance exercise associated or not with nandrolone decanoate (ND) on skeletal muscles and body mass of adult male rats. Training protocol consisted of 15 jump sessions, for 6 weeks. ND (5mg/kg) was administered twice a week. The exercise was effective in inducing respective enlargements in fiber areas of extensor digitorum longus and soleus muscles. ND associate with exercise was also able to induce increases in fiber areas these muscles. In untrained group that received nandrolone decanoate an improved in muscular parameters could be observed. In conclusion, the resistance exercise was able to promote an enlargement in fiber areas of both muscles studied without ND treatment, indicating that after a period of time of adaptation to exercise, the muscular effects caused by ND could be achieved in the same way by exercise, without ND and without risks for health.El objetivo de este estudio fue comparar los efectos del ejercicio de resistencia con o sin decanoato de nandrolona (DN) en el músculo esquelético y la masa corporal de ratas macho adultas. El protocolo de entrenamiento consistió en 15 sesiones durante 6 semanas de saltos. DN 5mg/kg se administró dos veces durante la semana. El ejercicio fue efectivo para inducir un aumento en el área de las fibras de los músculos extensor largo de los dedos y sóleo. El DN asociado con el ejercicio fue capaz de inducir un aumento en el área de las fibras de los músculos. En el grupo de DN sin entrenamiento, se observó un aumento en los parámetros musculares evaluados. El ejercicio de resistencia sin DN fue capaz de promover un aumento en el área de las fibras de los músculos, lo que indica que después de un período de adaptación al ejercicio, el efecto en los músculos causada por la DN se logró por el ejercicio, sin una gestión DN y los consiguientes peligros para la salud.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Antisperm antibodies in infertile men and their correlation with seminal parameters

Aim: Antisperm antibodies (ASA) in males cause the autoimmune disease 'immune infertility'. The present study intended to detect the presence of ASA and their incidence in men with unexplained infertility, as well as to evaluate the correlation between the presence of ASA and semen parameter alterations. Methods: Blood and sperm assessment were collected to carry out a direct and indirect mixed antiglobulin reaction (MAR) test and semen analysis in infertile and fertile men from the University Hospital of the Faculty of Medicine, Sao Paulo State University, Sao Paulo. Results: In the MARtest, 18.18% of infertile men were positive for ASA. In fertile men, no positivity was found. A significant correlation between the presence of ASA with an increased white blood cell count plus a decreased hypoosmotic swelling test result was observed. Conclusions: The results indicate that ASA are involved in reduced fertility. It is not ASA detection per.se that provides conclusive information about the occurrence of damage to fertility. The correlation between infertility and altered seminal parameters reinforce the ASA participation in this pathology. © 2007 The Authors Journal compilation. © 2007 Japan Society for Reproductive Medicine

Orchidectomy enhances the effects of phenylephrine in rat isolated portal vein

P>1. Orchidectomy results in long-term testosterone deprivation similar to that observed in male clinical pathologies, such as hypogonadism and age-related reductions in plasma testosterone concentrations. Although the vascular effects of these sorts of hormone deprivations are known in arteries, they have not been studied to the same extent in veins.2. The aim of the present study was to determine the effect of orchidectomy, with or without subsequent testosterone replacement (started 23 days after orchidectomy; 10 mg/kg, i.m., testosterone propionate once every 5 days for 3 weeks), on responses of rat isolated portal veins and vena cavae to exogenous phenylephrine (PE). Isolated vessels were mounted in an organ bath and concentration-response curves constructed to PE (10-10-10-4 mol/L), endothelin (ET; 10-10-10-5 mol/L) and KCl (10-2-1.2 x 10-1 mol/L; as a control).3. Orchidectomy had no effect on contractile responses of either the portal vein or vena cava to KCl. However, orchidectomy enhanced the maximum response (R(max)) of the portal vein, but not the vena cava, to PE. Testosterone replacement had no effect on these responses. The effects of orchidectomy on the R(max) to PE in portal veins were not altered by the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester (10-4 mol/L) alone or combined with 10-5 mol/L indomethacin (a non-selective cyclo-oxygenase inhibitor), but they were abolished following treatment of isolated vessels with the ET(A) and ET(B) receptor antagonists BQ-123 and BQ-788 (both at 10-6 mol/L). Orchidectomy did not alter portal vein responses to the application of exogenous ET.4. The results of the present study indicate that orchidectomy-induced decreases in plasma testosterone can increase the venoconstrictor effects of PE on the portal vein and that this effect involves activation of both ET(A) and ET(B) receptors by locally produced ET.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP