Different effects by sex on hypothalamic-pituitary axis of prepubertal offspring rats produced by in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP)

This study investigated the effect of pre and perinatal exposure to di-(2-ethylhexyl) phthalate (DEHP) on the neuroendocrine parameters that regulate reproduction in prepubertal male and female rats. DEHP at doses of 3 and 30 mg/kg. bw/day was administered orally in the drinking water to dam rats since pregnancy onset until the moment of pups sacrifice at 15 days of age. In these animals gonadotropin serum level and the hypothalamic contents of the amino acids aspartate, glutamate and gamma-aminobutyric acid were determined. No changes in gonadotropin levels and amino acid neurotransmitters were detected at the low dose in both sexes. However, DEHP administered at high dose (30 mg/kg bw/day) to dams produced a significant decrease in the inhibitory neurotransmitter GABA and an increase in the stimulatory neurotransmitter aspartate in prepubertal male offspring rats. These modifications were accompanied by gonadotropin serum levels increase. On the contrary, in treated female rats this chemical increased both, aspartate and GABA, which exert a characteristic stimulatory action on gonadotropin in 15-day-old normal females. This study provides new data about changes produced by DEHP on the hypothalamic amino acid neurotransmitters involved in the neuroendocrine reproductive regulation, in prepubertal male and female rat offspring from dams exposed during gestational and lactational periods. These alterations induced by DEHP exposure could be related to the gonadotropin modifications also described in this work, and with changes in the production of sexual hormones previously reported by other authors.Fil: Carbone, Silvia Elena. Universidad Favaloro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Samaniego, Yanina A.. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Cutrera, Rodolfo Angel. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Reynoso, R.. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Cardoso, N.. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Scacchi, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; ArgentinaFil: Moguilevsky, Jaime Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro; ArgentinaFil: Ponzo, Osvaldo Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentin

Influence of Normo- and Hypogonadal Condition, Hyperuricemia, and High-Fructose Diet on Renal Changes in Male Rats

Background. There is a gender disparity in the incidence, prevalence, and progression of renal disease. The object of this paper is to evaluate the presence and type of renal lesion in normogonadic and hypogonadic male rats in a mild hyperuricemia induced condition and exposed to a high-fructose diet. Methods. 56 adult male Wistar rats were used. Animals were divided into two groups, one normogonadic (NGN) and one hypogonadic (HGN), and each group was divided into four subgroups in accordance with the treatment: control with only water (C), fructose (F), oxonic acid (OA), and fructose + oxonic acid (FOA). Renal changes were evaluated by measuring glomerulosclerosis, fibrosis, and arteriolar media/lumen (M/L) ratio. Results. The OA and FOA groups presented significantly hypertension (p<0.001). The OA group significantly increased (p<0.05) the percentage of glomerulosclerosis as well as the FOA group (p<0.001). When comparing NGN versus HGN, we observed a trend to a lower glomerulosclerosis in the latter. A higher arteriolar M/L ratio was observed in the OA (p<0.05) and FOA (p<0.001). Conclusion. Hyperuricemia conditions and a high-fructose diet favor blood pressure increase together with changes in the arteriolar media/lumen ratio and renal glomerular damage. These changes were more apparent in normogonadic animals

Evidence of reproductive disruption associated with neuroendocrine changes induced by UV–B filters, phtalates and nonylphenol during sexual maturation in rats of both gender

Endocrine disruptors (EDs) are exogenous substances or xenoestrogens natural or synthetic, capable of interacting with different systems and altering their normal hormonal regulation, being the reproductive system one of the most affected. EDs produce their effects not only by acting on nuclear steroid receptors, but also on membrane receptors, steroidal and non-steroidal synthetic enzymatic pathways and/or metabolism. The incorporation to the body depend on each EDs, which are liposoluble and easily deposited in the tissue; thus ensuring a prolonged accumulation and release, even when the exposure is not continuous. In addition to cross the placenta, EDs may act in the offspring during the reproductive system formation and maturation key stages and its regulatory mechanisms. The effects of EDs can be multiple, but most acts mediating estrogenic and/or antiandrogenic effect. Three groups of EDs are widely used: in plastics (phtalates), sunscreens (cinnamate and methylbenzylcamphor), and detergents (nonylphenol). In this paper we review the effects of the exposure to these environmental chemicals on the reproductive system and the possible mechanisms by which they occur, focusing in the hypothalamic–pituitary neuroendocrine mechanisms that regulate the reproductive system.Fil: Ponzo, Osvaldo Juan. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Endocrinología; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina;Fil: Carbone, Silvia Elena. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Endocrinología; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina

Effect of N-Methyl-D-Aspartate Receptor Blockade on Anxiety-Like Behavior Induced in Rats by Postnatal Chronic Exposure to the Endocrine Disruptor Di-2 (Ethyl-Hexyl Phthalate) in Elevated plus Maze Test

Di-2-Ethylhexyl Phthalate (DEHP) is the widely used to convey flexibility and transparency to plastic products made of polyvinyl chloride and also in the manufacture of medical devices. DEHP disrupts reproductive tract development in an antiandrogenic manner and also may induce neurobehavioral changes. In previous works, we demonstrated that chronic postnatal exposure to DEHP alters the neuroendocrine regulation of the testicular axis, modifying the hypothalamic concentration of excitatory neurotransmitters and therefore induces an anxiogenic effect. In the Elevated Plus Maze (EPM) test, dizocilpine (MK-801) induces a decrease in anxiety-related behaviors throughout NMDA receptor blockade. The objective of this work was to investigate whether the blockade of NMDA receptors of glutamate by the non-competitive antagonist MK-801 could modify the anxiety-like behavior induced by chronic postnatal exposure to DEHP (30 mg/kg body weight/day, orally from birth) in young adult male rats in the EPM test. The results show that NMDA receptor blockade by MK-801 (0.1 mg/kg body weight, i.p.) in DEHP exposed animals is able to produce a significant decrease in time spent in closed arms (TSC) and in Freezing Time (FT) as well as an increase in time spent in open arms (TSO) in the EPM test, indicating an anxiolytic effect. In conclusion, our results suggest: 1) NMDA receptor blockade by MK-801 can reverse anxiety-like behavior induced by exposure to DEHP during the early period of life. 2) The glutamatergic system is involved in the anxiogenic effect of phthalate, which is probably triggered by its known antiandrogenic action.Fil: Carbone, Silvia Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Ponzo, Osvaldo Juan. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas; ArgentinaFil: Cutrera, Rodolfo Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentin

Leptin inhibits the reproductive axis in adult male Syrian hamsters exposed to long and short photoperiod

The aim of the study was to investigate the effects of acute leptin treatment of adult Syrian hamsters exposed to a long (LP, eugonadal males) and short photoperiod (SP, hypogonadal males). Animals were exposed to LP (L:D 14:10) or SP (L:D 10:14) for 10 weeks. Afterwards, both LP and SP hamsters were allocated to a control (SP-C, LP-C) or leptin-treated group (SP 3, SP 10, SP 30 or LP3, LP 10, LP 30). One hour before sacrifice, a single dose of leptin (3, 10 or 30 μg/kg) or vehicle was administered (i.p.) to the males. Testis weight, serum and pituitary luteinizing hormone (LH) concentrations, as well as the hypothalamic concentration of gonadotropin-releasing hormone (GnRH) were recorded. Histological analysis of the testis was performed and GnRH concentration in the culture medium of hypothalamic explants was examined. A dramatic regression of testicular weight and histological atrophy of seminiferous tubules, as well as a decrease in serum and pituitary LH concentrations were found in SP males. All doses of leptin significantly reduced serum LH levels and medium GnRH concentrations in both photoperiod groups. Pituitary LH and hypothalamic GnRH concentrations were not affected by leptin. In conclusion, we demonstrated that leptin inhibited the reproductive axis of Syrian male hamsters exposed to LP and SP and fed ad libitum.Fil: Boggio, Veronica Ines. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Fisiopatología; Argentina;Fil: Cutrera, Rodolfo Angel. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina;Fil: Carbone, Silvia Elena. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina;Fil: Scacchi, Pablo. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Endocrinología; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina;Fil: Ponzo, Osvaldo Juan. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Endocrinología; Argentina

Renal Damage During Continuous Versus Intermittent Treatment with Lithium

The aim of this study was to evaluate renal damage in animals treated with lithium continuously versus intermittently. Rats were randomized into three groups: control group fed ad libitum powered standard diet for 3 months and two experimental groups, one of them fed ad libitum the same diet or the same diet supplemented with 60 mmol of lithium/kg diet every alternate week, for 3 months and the other fed ad libitum powered standard diet for one and a half month and the same diet supplemented with 60 mmol of lithium/kg diet for the last month and a half. Lithemias in experimental groups were within therapeutic range used in humans. At the end of the protocol, diuresis was higher in experimental groups compared to control group. There was no difference in serum creatinine and creatinine clearance. Both experimental groups showed hypertrophy, hyperplasia, and dilatation of cortical collecting tubules although dilatation was greater in continuous group. Longer studies are necessary to clarify the evolution of renal damage. Our preliminary study shows that histopathological damage associated with the use of lithium occurs during both continuous and intermittent treatment, but it seems to be somewhat greater in the continuous group.Fil: Ossani, Georgina Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Aleman. Laboratorio de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología; ArgentinaFil: Uceda, Ana Margarita. Hospital Aleman. Laboratorio de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología; ArgentinaFil: Ponzo, Osvaldo Juan. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Lago, Néstor R.. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología; ArgentinaFil: Martino, Diego Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; Argentin

Interrelationships of gabaergic, serotoninergic and excitatory amino acid systems in its regulatory effect on prolactin secretion in prepubertal rats

GABAergic, serotoninergic and excitatory amino acid systems (EAAs) regulate the prolactin (PROL) secretion in prepubertal female rats. The aim of the present paper was to determine the interrelationships of these systems on the control of this pituitary hormone. It was carried out through the following scheme: 1. The participation of the EAAs and serotonin in the effect of GABAergic system on PROL release, determined by evaluating the GABA A and GABA B receptor agonists. It was carried out on animals that were previously treated with AAES receptor antagonist or p-chlorophenylamphetamine (PCA), this one depleting serotonin in the hypothalamus. 2. The participation of GABAergic system in the effect of serotonin and EAAs systems, determined by the evaluation of the effects of EAAs receptor agonists and of 5-HTP, a serotonin precursor. With this purpose the rats were previously treated with GABA A and GABA B receptor antagonists. 3. The interrelationships between the EAAs and the serotoninergic systems in the control of PROL secretion, determined (a) by using EAAs agonists (in rats depleted of serotonin by PCA) and (b) using EAAs antagonists (in rats treated with 5-HTP, a serotonin precursor). The administration of GABAergic agonists significantly increased PROL secretion in prepubertal female rats. Neither EAAs antagonists nor the depletion of serotonin in the brain, modified the stimulatory effects of the GABAergic system on PROL levels. This is a clear indication that the activity of the GABAergic system is independent of the serotoninergic and of the EAAs system effects on the pituitary hormone. The EAAs neurotransmitter system agonists significantly increase PROL levels. This effect was blocked by the GABAergic system antagonists but was not modified by serotonin depletion. Taking into account these facts it may be considered that the GABAergic system is involved in the stimulatory effect of EAAs on PROL secretion, this effect being independent of the serotoninergic system. 5-HTP significantly increased PROL plasma levels, and this effect was modified neither by the GABAergic nor by the EAAs receptor antagonists. These results indicate that the stimulatory effect of serotonin on PROL release is independent of the GABAergic and EAAs systems. In conclusion it may be considered that in prepubertal female rats, the GABAergic and serotoninergic systems stimulate PROL secretion by independent mechanisms that do not include EAAs. On the other hand, the effects of EAAs neurotransmission are exerted via the GABAergic system.Fil: Moguilevsky, Jaime Alberto. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Szwarcfarb, Berta. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Carbone, Silvia Elena. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rondina, Dora. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Ponzo, Osvaldo Juan. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Scacchi, Pablo. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Effects of a low dose of bisphenol A on the reproductive axis of prepuberal male rats

El objetivo del presente trabajo fue estudiar el efecto de una dosis baja de bisfenol A (BPA) sobre el eje reproductor de ratas macho prepúberes, expuestas durante la gestación y la lactancia. Se trató a ratas hembra preñadas con una dosis aproximada de exposición de BPA de 3 mg, administrado en el agua de bebida, y el tratamiento continuó durante la lactancia. Las crías macho fueron sacrificadas a los 35 días de vida, etapa prepuberal. Se evaluó el peso corporal durante el desarrollo de las crías y al momento del sacrificio, como así también los pesos testiculares y de vesículas seminales y sus respectivos pesos relativos. Las ratas se sacrificaron por decapitación y se recolectó sangre troncal para la determinación de LH, FSH y testosterona. Se realizó además estudio histológico de tejido testicular. El peso corporal al momento del sacrificio fue significativamente superior en el grupo expuesto a BPA en comparación con el grupo control; el peso testicular disminuyó significativamente; el peso de vesículas seminales y los pesos relativos de testículo y de vesículas seminales no se modificaron con el tratamiento. Los niveles de LH y FSH se incrementaron significativamente con el tratamiento y los de testosterona no mostraron cambios significativos. El estudio histológico mostró la luz de los túbulos seminíferos disminuida por la presencia de células inmaduras de la serie espermática. Nuestros resultados demuestran que la exposición a bajas dosis de BPA durante la gestación y la lactancia altera la normal función del eje reproductor de ratas macho prepúberes.Fil: Gámez, Juan Manuel. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Endocrinología; Argentina; Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas; Argentina; Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental. Laboratorio de Neuroendocrinología y Comportamiento; Argentina;Fil: Penalba, Romina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Endocrinología; Argentina; Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas; Argentina; Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental. Laboratorio de Neuroendocrinología y Comportamiento; Argentina;Fil: Cardoso, Nancy Patricia. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Endocrinología; Argentina; Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas; Argentina; Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental. Laboratorio de Neuroendocrinología y Comportamiento; Argentina;Fil: Ponzo, Osvaldo Juan. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Endocrinología; Argentina; Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas; Argentina; Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental. Laboratorio de Neuroendocrinología y Comportamiento; Argentina;Fil: Carbone, Silvia Elena. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Endocrinología; Argentina; Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas; Argentina; Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental. Laboratorio de Neuroendocrinología y Comportamiento; Argentina;Fil: Pandolfi, Matias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental; Argentina; Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Endocrinología; Argentina; Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental. Laboratorio de Neuroendocrinología y Comportamiento; Argentina;Fil: Scacchi, Pablo. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Endocrinología; Argentina; Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas; Argentina; Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental. Laboratorio de Neuroendocrinología y Comportamiento; Argentina;Fil: Reynoso, Roxana María. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Endocrinología; Argentina; Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas; Argentina; Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental. Laboratorio de Neuroendocrinología y Comportamiento; Argentina

Endogenous hypertriglyceridemia intensifies the course of cerulein-induced pancreatitis in rat: Relation with changes in the VLDL composition

Aims: To study if the course of cerulein-induced pancreatitis in rats changes in a state of triglyceride-rich lipoprotein metabolism alteration. Methods: Two groups of rats received control diet during a 90-day period (A) and sucrose-rich diet to induce endogenous hypertriglyceridemia (B). Subgroups A2 and B2 received i.p. 45 μg cerulein/kg body weight (to induce acute pancreatitis). Histological examination of pancreas tissue, serum pancreatic lipase, lipoprotein profile and VLDL chemical composition were assessed. Then, pancreatic lipase hydrolytic activity on VLDL-triglycerides was evaluated in vitro. Results: Cellular vacuolization was observed in all of the cerulean-injected rats, but only in subgroup B2 fat necrosis was present. Serum triglycerides were higher in subgroup B1 than in subgroup A1 (mean ± SEM, mg/ dl 123,77 ± 25.7 vs. 65.8 ± 7, p < 0.01). Triglycerides from rats fed with sucrose-rich diet, decreased after cerulein-induced pancreatitis (80.38 ± 11.3 vs. 123,77 ± 25.7, p < 0.02). Moreover, the endogenous hypertriglyceridemic rats showed an increment of VLDL triglyceride content, which decreased when rats were injected with cerulein. A negative correlation was found between VLDL-triglyceride content and serum pancreatic lipase activity (r = 0.58, p < 0.02). The in vitro assay showed a decrease in VLDL-triglyceride content post incubation with pancreatic lipase enriched serum (mean ± SD: 59.2 ± 27.7%, p < 0.01). Conclusions: The endogenous hypertriglyceridemia intensifies the course of cerulein-induced pancreatitis and it could be related to the decrease in VLDL-triglycerides as a consequence of pancreatic lipase hydrolytic activity.Fil: Ponzo, Osvaldo Juan. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; ArgentinaFil: Schreier, Laura Ester. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; ArgentinaFil: Resnik, R.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; ArgentinaFil: Negri, Gustavo Alberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; ArgentinaFil: Scacchi, Pablo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Cresta, M. A.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; ArgentinaFil: Wikinski, R.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentin

Effect of di(2-ethylhexyl) phthalate on the neuroendocrine regulation of reproduction in adult male rats and its relationship to anxiogenic behavior: Participation of GABAergic system

The endocrine disruptor di-(2-ethylhexyl) phthalate (DEHP) is used in a variety of consumer products made with polyvinyl chloride and also in the manufacture of medical devices. DEHP disrupts reproductive tract development in an antiandrogenic manner and also may induce neurobehavioral changes. The aim of this study was to investigate the effects of chronic postnatal exposure to DEHP (30 mg/kg body weight/day, orally from birth to day 60) on the neuroendocrine regulation of the gonadal axis and its impact on the anxiety-like behavior in adult male rats, as well as the probable participation of the GABAergic system in these effects. DEHP produced a significant increase in plasmatic luteinizing hormone and follicle stimulating hormone, as well as significant testosterone decrease, accompanied with a decrease in hypothalamic gamma-aminobutyric acid (GABA) concentration. On the other hand, DEHP increased the anxiety-like behavior in the elevated plus maze test, evidenced by a significant decrease in the percentages of time spent in the open arms and the frequency in the open arm entries and a significant increase in the percentage of time spent in closed arms. Neuroendocrine and behavioral effects were reversed by GABA agonists, muscimol (2 mg/kg i.p.) and baclofen (10 mg/kg i.p.). In conclusion, chronic DEHP postnatal exposure induced a disruption in the neuroendocrine regulation of the testicular axis in young adult male rats, and this effect was correlated with an anxiety-like behavior. Since GABA agonists reversed these effects, the results suggest that GABA could participate in the modulation of reproductive and behavioral DEHP effects.Fil: Carbone, Silvia Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Ponzo, Osvaldo Juan. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gobetto, María Natalia. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Samaniego, Y.A.. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Reynoso, R.. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Moguilevsky, Jaime Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro; ArgentinaFil: Cutrera, Rodolfo Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentin