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J Reprod Immunol ; 131: 1-6, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30390547


This retrospective study of prospectively collected data examines the effect of prednisolone therapy on raised uterine Natural Killer cell (uNK) concentrations and pregnancy outcomes in women with recurrent miscarriage (RM) and recurrent implantation failure (RIF) after IVF/ICSI treatment. 136 women diagnosed with RRF who had a timed midluteal endometrial biopsy taken for uNK cell analysis were included. Women with high uNK cell concentrations (n = 45) were treated with prednisolone (10 mg/day) for one month, after which a second biopsy was taken for repeat uNK cell analysis. Women for whom prednisolone caused a decrease in uNK cell concentrations continued on prednisolone until 12 weeks of pregnancy. Pregnancy outcomes (live birth, miscarriage and implantation rates) and pregnancy complications were compared for women who received prednisolone and those who did not. Results showed that the prevalence of high uNK cells was 33.1%. Prednisolone significantly decreased the uNK cell concentration (P < 0.001), however reduction to normal limits was achieved in only 48.3% of patients. There was no difference in any of the pregnancy outcomes or complications between women who had received prednisolone and those who had not. In conclusion, this study showed a relatively high prevalence of raised uNK cells in women with recurrent reproductive failure and confirmed the effect of prednisolone on reducing uNK cell concentrations. We found however no evidence for a significant beneficial effect for prednisolone therapy on pregnancy outcomes. Until the results of an adequately powered RCT become available however, these findings should be considered preliminary.

Aquat Toxicol ; 202: 105-116, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30014986


In the present study, we examined the subcellular distribution of metals and metalloids (As, Cd, Cu, Se and Zn) in the liver and gonads of wild white suckers (Catostomus commersonii) collected downstream from a metal mining operation (exposure area) and in a reference area. Metal partitioning among potentially metal-sensitive fractions (heat-denatured proteins (HDP), mitochondria and microsomes) and potentially biologically detoxified fractions (heat-stable proteins (HSP) and metal-rich granules) within cells was determined after differential centrifugation, NaOH digestion and heat-denaturation steps. Metal-handling strategies between liver and gonads, and between sexes, were examined. Hepatic metal concentrations were significantly higher in exposed compared to reference fish, especially for Se (14x), Cd (5x) and Cu (3x), and did not vary between sexes. In contrast, gonadal Cd, Cu, Se and Zn concentrations were consistently lower in testes than in ovaries; marked differences in Cd and Se concentrations between exposed and reference fish were observed for both sexes. Overall, metal-handling strategies were similar in both liver (male and female pooled) and female gonads, but differed from those in male gonads, likely due to the different functions assigned to ovaries and testes. Subcellular partitioning of As, Cd and Cu showed that the HSP fraction was most responsive to increased metal exposure, presumably reflecting Cu regulation, and possibly Cd and As detoxification. Zinc concentrations were tightly controlled and mainly found in the HDP fraction. Interestingly, changes in Cd-handling strategy in female gonads were particularly evident, with Cd shifting dramatically from the metal-sensitive HDP fraction in reference fish to the metal-detoxified HSP fraction in exposed fish. It seems that Cd detoxification in female gonads was not fully induced in the less contaminated fish, but became more effective above a threshold Cd concentration of 0.05 nmol/g dry weight. Partitioning of Se was different, with the largest contributor to the total liver and gonad Se burdens being the putative metal-sensitive HDP fraction, suggesting that excess Se in this fraction in exposed fish may lead to Se-related stress. The present subcellular partitioning results demonstrate that metal handling strategies vary among metals, between organs and (in some cases) as a function of metal exposure. They also show promise in identifying metals of potential concern in a risk assessment context.

Metais/metabolismo , Poluentes Químicos da Água/metabolismo , Animais , Arsênico/química , Arsênico/metabolismo , Arsênico/toxicidade , Cádmio/química , Cádmio/metabolismo , Cádmio/toxicidade , Cobre/química , Cobre/metabolismo , Cobre/toxicidade , Cipriniformes , Feminino , Gônadas/efeitos dos fármacos , Gônadas/metabolismo , Inativação Metabólica , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Metais/química , Metais/toxicidade , Mineração , Selênio/química , Selênio/metabolismo , Selênio/toxicidade , Poluentes Químicos da Água/química , Poluentes Químicos da Água/toxicidade , Zinco/química , Zinco/metabolismo , Zinco/toxicidade
Aquat Toxicol ; 132-133: 73-83, 2013 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-23466431


The objective of the present field experiment was to identify detoxification responses in the gills and digestive gland of a freshwater unionid bivalve, Pyganodon grandis, subjected to a step-change in metal exposure. Adult bivalves were transferred from a reference site (Lake Opasatica) and a metal-contaminated lake (Lake Héva) to a second contaminated lake (Lake Vaudray) in northwestern Quebec, Canada. Changes in organ metal concentrations, in the subcellular distribution of metals and in metallothionein concentrations were followed over time (t=0, 132, (400) and 860 days). At each collection time and for each bivalve, the gills and digestive gland were excised and gently homogenized; six sub-cellular fractions were separated by differential centrifugation and analyzed for their Cd, Cu and Zn content, and metallothionein was quantified independently. Metal detoxification strategies were shown to differ between target organs: in the gills, incoming metals were sequestered largely in the granules, whereas in the digestive gland the same metals primarily accumulated in the cytosol, in the metallothionein-like protein fraction. These metal-handling strategies, as employed by the metal-naïve bivalves originating in the reference lake, closely resemble those identified in free-living P. grandis chronically exposed in the metal-contaminated lake, suggesting that the ability to handle incoming metals (Cd in particular) is inherent in P. grandis and is not a trait acquired after long-term adaptation of the bivalve to metal-contaminated environments. The bivalves transplanted from both Lakes Opasatica and Héva were able to tolerate their new surroundings during the first 400 days of the transplant experiment, as indicated by the absence of mortality and the presence of gravid animals. Over the final 460 days, mortality remained low for the bivalves transplanted from the reference lake (20%) but reached 100% in the transplanted group from the contaminated lake. It would seem that the Lake Héva bivalves were compromised by their initial exposure to metals in their home lake and that the added stress of being transplanted to and caged in a lake with comparable or slightly higher concentrations of metals was sufficient to cause mortality.

Lagos/análise , Metalotioneína/metabolismo , Metais Pesados/farmacocinética , Unionidae/efeitos dos fármacos , Poluentes Químicos da Água/farmacocinética , Animais , Cádmio/farmacocinética , Cobre/farmacocinética , Monitoramento Ambiental , Inativação Metabólica , Quebeque , Estações do Ano , Espectrofotometria Atômica , Distribuição Tecidual , Unionidae/metabolismo , Zinco/farmacocinética
Aquat Toxicol ; 100(4): 303-12, 2010 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-20843564


The dynamics of cadmium uptake and subcellular partitioning were studied in laboratory experiments conducted on Pyganodon grandis, a freshwater unionid bivalve that shows promise as a biomonitor for metal pollution. Bivalves were collected from an uncontaminated lake, allowed to acclimate to laboratory conditions (≥25 days), and then either exposed to a low, environmentally relevant, concentration of dissolved Cd (5nM; 6, 12 and 24h), or fed Cd-contaminated algae (∼70nmol Cdg⁻¹ dry weight; 4×4h). In this latter case, the bivalves were allowed to depurate for up to 8 days after the end of the feeding phase. As anticipated, the gills were the main target organ during the aqueous Cd exposure whereas the intestine was the initial site of Cd accumulation during the dietary exposure; during the subsequent depuration period, the dietary Cd accumulated in both the digestive gland and in the gills. For the gills, the distribution of Cd among the subcellular fractions (i.e., granules>heat-denatured proteins (HDP)∼heat-stable proteins (HSP)>mitochondria∼lysosomes+microsomes) was insensitive to the exposure route; both waterborne and diet-borne Cd ended up largely bound to the granule fraction. The subcellular distribution of Cd in the digestive gland differed markedly from that in the gills (HDP>HSP∼granules∼mitochondria>lysosomes+microsomes), but as in the case of the gills, this distribution was relatively insensitive to the exposure route. For both the gills and the digestive gland, the subcellular distributions of Cd differed from those observed in native bivalves that are chronically exposed to Cd in the field - in the short-term experimental exposures of P. grandis, metal detoxification was less effective than in chronically exposed native bivalves.

Cádmio/metabolismo , Espaço Intracelular/metabolismo , Unionidae/metabolismo , Poluentes Químicos da Água/metabolismo , Animais , Cádmio/análise , Dieta , Sistema Digestório/metabolismo , Relação Dose-Resposta a Droga , Exposição Ambiental/análise , Água Doce/química , Brânquias/metabolismo , Poluentes Químicos da Água/análise
Ecotoxicol Environ Saf ; 73(3): 391-9, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20047761


Among the various anthropogenic activities potentially affecting amphibian populations, agriculture has often been evoked. Fertilizers used in agriculture are documented sources of metals that may contaminate nearby rivers. Bullfrogs (Rana catesbeiana) were collected within the Yamaska River basin (Quebec, Canada) along a gradient of agricultural land use intensity. Hepatic, renal and intestinal metal content, along with hepatic metallothionein content, were determined. In general, dissolved metal concentrations and accumulated metal concentrations in bullfrogs varied little among sites. Hepatic Cu and Zn concentrations were significantly different among subwatersheds and were in accordance with the gradient in agricultural activities in at least one of the three years studied. Liver metallothionein content did not vary significantly among the subwatersheds, but they were correlated with Cu content within two sites and Cd content at one site. We conclude that R. catesbeiana could be used as a biomonitor for Cu contamination and potentially for other metals.

Agricultura , Resíduos Industriais/efeitos adversos , Metais Pesados/toxicidade , Rana catesbeiana/fisiologia , Poluentes Químicos da Água/toxicidade , Animais , Biomarcadores/análise , Biomarcadores/metabolismo , Monitoramento Ambiental/métodos , Fertilizantes/efeitos adversos , Água Doce/química , Mucosa Intestinal/metabolismo , Intestinos/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Metalotioneína/efeitos dos fármacos , Metalotioneína/metabolismo , Metais Pesados/análise , Metais Pesados/metabolismo , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/metabolismo , Poluição da Água , Abastecimento de Água/análise