RESUMO
Cadmium (Cd) is toxic to the skeletal system resulting in bone loss and pain. We aimed at determining the effect of chronic Cd exposure on bone density and microarchitecture along with changes in the density of a subset of sensory and sympathetic nerve fibers innervating the developing rat femur. Newborn male Wistar rats were injected daily for 49 days with CdCl2 (1 mg/kg i.p.) or saline solution (control group). At the day of sacrifice, levels of Cd in the right femur, liver and kidney were determined by atomic absorption spectrophotometry. Additionally, microCT followed by immunohistochemical analyses were performed in the left femur. Results showed Cd accumulation in trabecular bone neared levels seen in liver and kidney. Cd concentration in cortical bone was significantly lower versus trabecular bone. MicroCT analysis revealed that Cd-exposed rats had a significant decrease in trabecular bone parameters at the distal femoral metaphysis; however, most of the cortical bone parameters were not significantly affected. Cd-exposed rats showed a significant loss of TH+ sympathetic nerve fibers, but not of CGRP+ sensory nerve fibers, at the level of bone marrow of the femoral diaphysis as compared to control rats. This study shows that Cd negatively affects bone density and microarchitecture of trabecular bone and decreases the density of sympathetic nerve fibers innervating rat femur. Future studies are warranted to determine the toxigenic mechanisms of Cd on sympathetic nerves and how sympathetic denervation influences bone loss in animals exposed to Cd.
Assuntos
Densidade Óssea/efeitos dos fármacos , Cádmio/toxicidade , Osso Esponjoso/efeitos dos fármacos , Fêmur/efeitos dos fármacos , Fibras Nervosas/efeitos dos fármacos , Animais , Cádmio/administração & dosagem , Feminino , Fêmur/crescimento & desenvolvimento , Injeções Intraperitoneais , Gravidez , Ratos , Ratos WistarRESUMO
Cadmium (Cd) is a heavy metal related to a decrease in sperm parameters. The transit of spermatozoa through the epididymis is necessary to generate changes in the sperm membrane, such as the assembly of various carbohydrates that are added to the spermatazoan's surface to prepare it for successful fertilisation of the oocyte. No studies have yet analysed whether Cd alters the presence and distribution of these carbohydrates. We aimed to evaluate the changes induced by Cd in the distribution pattern of N-acetylglucosamine, sialic acid, mannose and fucose on the sperm membrane in the epididymis (e.g. caput, corpus, cauda) and if it alters the epididymal epithelium. Male Wistar pups were treated with Cd doses (0.125, 0.25 and 0.5mg/kg) on postnatal days 1-49. At postnatal day 90, they were humanely killed, sperm samples were obtained from the epididymis and tissue samples were taken for histological analysis. Cd concentrations in the blood and epididymis increased in proportion to the dose administered and decreased the serum testosterone levels and sperm quality. Histological analysis revealed alterations in the epithelium in all Cd-treated groups. Cd altered the distribution patterns of carbohydrates and fluorescence indices. All these alterations affected the structure and functioning of sperm.
Assuntos
Cádmio/administração & dosagem , Carboidratos/análise , Membrana Celular/química , Epididimo/crescimento & desenvolvimento , Maturação do Esperma/efeitos dos fármacos , Espermatozoides/crescimento & desenvolvimento , Acetilglucosamina/análise , Animais , Cádmio/análise , Membrana Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Epididimo/química , Epididimo/citologia , Fucose/análise , Masculino , Manose/análise , Ácido N-Acetilneuramínico , Ratos , Ratos Wistar , Espermatozoides/efeitos dos fármacos , Espermatozoides/ultraestrutura , Testosterona/sangueRESUMO
There are numerous evidence showing that cadmium (Cd) is an endocrine disruptor that exerts multiple toxic effects at different reproductive levels, including male sexual behavior (MSB). The effect of early exposure to Cd on sexual incentive motivation (SIM) and MSB in adult stage, and the immunoreactivity of receptors for hormones such as estrogens and androgens in brain regions that are relevant for the SIM and MSB display, have not been studied until now. The present study evaluated the effects of 0.5 and 1 mg/kg CdCl2 from day 1-56 of postnatal life on SIM and MSB in adults rats, as well as serum testosterone concentrations, Cd concentration in blood, testis, and brain areas, and the immunoreactivity in estrogen receptors (ER-α and -ß), and androgen receptor (AR) in the olfactory bulbs (OB), medial preoptic area (mPOA), and medial amygdala (MeA). Our results showed that both doses of Cd decreased SIM and MSB, accompanied by low serum concentrations of testosterone. Also, there was a significant reduction in immunoreactivity of ER-α and AR in mPOA, and a significant reduction in AR in MeA on male rats treated with Cd 1 mg/kg. These results show that exposure to high doses of Cd in early postnatal life could alter the correct integration of hormonal signals in the brain areas that regulate and display SIM and MSB in adult male rats.
Assuntos
Cádmio , Motivação , Ratos , Animais , Masculino , Cádmio/metabolismo , Receptores Androgênicos/metabolismo , Comportamento Sexual Animal , Encéfalo/metabolismo , Estrogênios/farmacologia , Testosterona , Receptores de Estrogênio/metabolismoRESUMO
In industrialized countries, the use of Cadmium (Cd) produces a form of anthropogenic pollution. Hence, exposure by human populations is becoming a public health problem. With a half-life of up to 40 years, cadmium is now a topic of great interest due to its role as an endocrine disruptor and its effects on male reproduction. Cd's diverse toxic mechanisms are based on its capacity to mimic divalent ions -calcium, zinc, iron- that participate in physiological processes. It alters the mitochondrial function and generates the production of free radicals that can induce apoptosis. In male reproduction, Cd alters the precise coordination of the hypothalamic-hypophysis-testis axis (HHT), resulting in the loss of testicular functions like steroidogenesis, spermatogenesis and the onset of puberty, sexual maturity, sexual behavior and fertility. Exposure to Cd may even cause changes in the immune system that are associated with the reproductive system. This review analyses the state of the question regarding Cd's cellular and physiological mechanisms and the effects of this heavy metal on the neuroendocrine regulation of male reproduction.
Assuntos
Cádmio/toxicidade , Sistemas Neurossecretores/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Animais , Masculino , Testículo/efeitos dos fármacosRESUMO
Puberty is a transitional period from juvenile stage to adulthood, followed by the functional maturation of gonads and reproductive organs. This period is sensitive to environmental pollutants like cadmium (Cd), a heavy metal that represents a serious health risk. Cd is an endocrine disruptor that interferes with reproduction by causing oxidative stress in the reproductive organs, affecting the sexual function and decreasing testosterone (T) levels. However, little research has been done on the effects of Cd on puberty markers and antioxidant systems. In this study, we evaluated the effects of Cd on puberty markers: preputial separation, testes descent and T levels, and the antioxidant activity (SOD, CAT, GSH/GSSG and TAC) in the seminal vesicles, testis and epididymis. Male Wistar pups were treated with 1â¯mg/kg Cd or saline solution by i.p. injection from day 1 to 35; the other treatment was administrated for 49 days. At the end of treatment, the animals were sacrificed, and the tissues of interest dissected, weighed and prepared for the respective assays. Cd treated rats from birth to puberty showed a delay onset in the puberty markers and a low weight in reproductive organs. Also, Cd induced differential effects on the redox system in reproductive organs and decreased T levels, these effects played a pivotal role in the delay of puberty markers onset (testes descent and preputial separation), affecting the development and sexual maturity of the male rats.