Description
Numerous reports indicate a decrease in the quality and quantity of sperm both in humans and wild animals. This is also associate to an increase of testicular cancer rate and gonadal disfunctions. The origin of a high proportion of cases of idiophatic male infertility could be related with these events. Environmental contaminants such as the so called "endocrine disrupters" are being pointed out as a main cause of such disfunctions. Endocrine disrupters are a wide group of compounds, which acting as endocrine deregulators, could generate gene deregulation depending of the genetic background of the organisms. The reproductive systems have been considered as crucial target of the impact of these compounds. We have been most interested in the assessment of gene deregulation in developing testis in animals and cells exposed to endocrine disrupters. To this aim, different approaches are being carried out including functional genomics and proteomics. In previous studies, we have isolate and cloned more than 200 different cDNAs corresponding to genes expressed in gametic cells potentially targets to be deregulated by reprotoxicants including Endocrine disrupters. This has been the base to generate a prototype of microarray with oligos from 300 specific genes (GENDISRUPT-1). DNA microarrays that include the total mouse transcriptome (28.878 genes) were also used to analyse patterns of gene expression in testicular cells exposed both in vitro and in vivo to endocrine disrupters compounds. The analyses are being enhanced by the use of 2D electrophoretic gels and protein identification in cells and gonads from mice exposed to these reprotoxicants (see the line: proteomics in spermatogenesis). To this respect, we have jointly assessed the effect of five compounds, administered by drinking water, in 3 different dosages and at three times during development: mothers before mating, during embryonic period and during puberal time. The compounds used in this study were: 17-beta-estradiol (as a natural oestrogen), bisphenol A (a component of polycarbonated plastics), monoesther of phthlate (a metabolite of plasticers), lindane (an organochlorine used as a pesticide) and zearalenone (a phytoestrogen contaminant of cereals). The results from the analysis of more than 3 million data from microarrays shown as more prominent aspects that, concerning gene deregulation: a) a low dosage effect (higher effect at low than at high dosage) is clearly detected, mainly for phthalate and lindane. b) some compounds, as zearalenone, shown a remarkable effect in animals whose mothers were exposed before conception. c) phthalate and zearalenone displayed an specific, different an and more severe "genetic signature" of deregulation than those observed for estradiol.
Association of these studies to male infertility or testicular cancer are also part of our objectives.
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