Sex-specific effects of neonatal exposures to low levels of cadmium through maternal milk on development and immune functions of juvenile and adult rats

University of Liège, Luik, Wallonia, Belgium
Toxicology (Impact Factor: 3.62). 06/2005; 209(3):289-301. DOI: 10.1016/j.tox.2004.12.007
Source: PubMed


Cadmium (Cd) is a major environmental contaminant. Although immunotoxic effects have been associated with Cd exposure, the inconsistency of experimental results underlines the need of an experimental approach more closely related to environmental conditions. We investigated the effects of exposing neonatal Sprague-Dawley rats to environmentally relevant doses of Cd through maternal milk. Dams received 10 parts per billion (ppb) or 5 parts per million (ppm) Cd chloride (CdCl2) in drinking water from parturition until the weaning of the pups. Half of the offspring was sampled at weaning time. The remaining juvenile rats received water without addition of Cd until adulthood. Cd accumulation in kidneys of juvenile rats fed from dams exposed to Cd indicated the transfer of the metal from mother to pups through maternal milk. This neonatal exposure resulted in decreased body, kidney and spleen weights of just weaned females but not of males. This effect was more pronounced in the less exposed females fed from dams exposed to 10 ppb Cd, which also displayed lower hepatic metallothionein-1 (MT-1) mRNA levels. The effect of Cd exposure on body and organ weights did not persist to adulthood. In contrast, we observed gender-specific effects of neonatal Cd exposure on the cytotoxic activity of splenic NK-cells of both juvenile and adult rats. Cd also strongly inhibited the proliferative response of Con A-stimulated thymocytes in both male and female adult rats 5 weeks after the cessation of Cd exposure. These immunotoxic effects were observed at doses much lower than those reported to produce similar effects when exposure occurred during adulthood. In conclusion, neonatal exposures to environmentally relevant levels of Cd through maternal milk represent a critical hazard liable to lead to both transitory and persistent immunotoxic effects.

Download full-text


Available from: Andrew Rooney, Aug 07, 2014
  • Source
    • "Pero estos sistemas de transporte también se encuentran alterados en la exposición translactacional al cadmio (Pillet et al. 2005). Esto demostraba que el cadmio obtenido a través de la leche materna es suficiente para causar alteraciones fisiológicas en las crías. "
    [Show abstract] [Hide abstract]
    ABSTRACT: El cadmio es un metal pesado que de manera natural se encuentra en muy bajas concentraciones en el medio ambiente, sin embargo, el uso de fertilizantes agrícolas que contienen fosfatos presentan niveles altos de cadmio, lo que provoca la contaminación de los suelos y en consecuencia de la vegetación que en ellos crece. Otras fuentes de contaminación ambiental con cadmio son el humo del tabaco y la actividad industrial que produce zinc. (Satarug et al. 2006). Estudios realizados in vivo sugieren que el cadmio ingerido con los alimentos se deposita directamente en el riñón, ya que al ingresar al organismo a bajas dosis se une a metalotioneinas que son filtradas y absorbidas en el riñón (Elsenhans et al. 1997). En la medula renal se deposita a bajas concentraciones, mientras que en la corteza se encuentra en grandes cantidades, principalmente en las células del túbulo proximal que es donde se lleva a cabo la mayor absorción del cadmio filtrado (Jarup et al. 1998).
    Full-text · Conference Paper · Dec 2008
  • Source
    • "These effects did not persist to adulthood. However, we have demonstrated sexspecific immunotoxic effects of neonatal exposure to these low levels of Cd, specifically on the cytotoxic activity of splenic natural killer (NK) cells of both juvenile and adult rats (Pillet et al., 2005). "
    [Show abstract] [Hide abstract]
    ABSTRACT: A wide range of toxic effects has been associated with cadmium (Cd) exposure in mammals. However, the physiological factors that modulate these effects have received limited attention. We have previously demonstrated that neonatal exposure of rats to Cd during lactation results in sex-specific immunotoxic effects in both juvenile and adult rats. The objectives of this study were to determine the effects of 17β-estradiol (E2) on the immunotoxicity of Cd in female rats. We compared the effects of 28 days of exposure to 0, 5, and 25 ppm cadmium chloride (CdCl2) through drinking water on ovariectomized Sprague-Dawley rats and on ovariectomized rats with E2 implant which mimicked the physiological level of E2 in female rat. Our results clarify the control of important immune functions by E2 at physiological level and demonstrate significant interactions between Cd and E2 effects on the cytotoxic activity of natural killer cells and phagocytosis of splenic cells as well as on the total number of thymocytes and of the four subpopulations of the thymocytes as defined by the expression of the cell-surface markers CD4 and CD8. Cd and E2 share several mechanisms of action that may account for these interactions. The estrogenic potential of Cd could also account for some of the observed effects. These interactions have to be taken into consideration in evaluating the risk of Cd immunotoxicity and the possible interactions with hormonal treatments.
    Full-text · Article · Sep 2006 · Toxicological Sciences
  • Source
    • "The primary route of Cd exposure is contaminated water or food supplies (Leffel et al., 2003; Satarug and Moore, 2004), smoking (Satarug and Moore, 2004), mother's milk (Pillet et al., 2005), through work in battery factories (Sahmoun et al., 2005), or through fertilizers or indiscriminate use of pesticide (Weggler et al., 2004). Cadmium is toxic to humans and animals and excessive exposure to it results in diseases and occasionally death (Othumpangat et al., 2005). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Among environmental contaminants known for their toxicity and worldwide distribution, heavy metals are of primary concern. Although the toxicology of cadmium (Cd) has been extensively studied, little information is available on the immunomodulation driven by exposure to low doses of Cd. We aimed to evaluate the immunomodulatory effects elicited by short-term exposure of human immunocompetent cells to low biologically relevant doses of Cd in two activation models. Human peripheral blood mononuclear cells, activated either by bacterial antigens (heat-killed Salmonella Enteritidis) or monoclonal antibodies (mAb: anti-CD3/anti-CD28/anti-CD40), were exposed to Cd acetate for 24h. Cell vitality was determined by MTT assay, cytokine release by ELISA, and cytokine gene expression by real-time RT-PCR. The results demonstrated that, in addition to the known toxic effects of Cd, doses from 0.013 to 13.3 microM exert differential effects on cytokine production. In the case of mAb-activation, secretion of interleukin (IL)-1 beta, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma was greatly inhibited at low Cd doses compared to production of IL-4 and IL-10. This indicates a type-2-biased immune response. Under stimulation by bacterial antigens, release of IL-10 was highly suppressed compared to that of IFN-gamma and TNF-alpha; IL-4 was undetectable. These results imply that low Cd doses exert immunomodulatory effects and the direction of this modulation depends on the pathway to cell activation. Overall, Cd polarizes the immune response toward type-2 in cells stimulated via T cell receptors. However, a polarized type-1 response induced by bacterial antigens could not be overwhelmed by the effects of Cd.
    Full-text · Article · Jun 2006 · Toxicology
Show more