Bellingham M, McKinnell C, Fowler P A, Amezaga M R, Zhang Z, Rhind S M, Cotinot C, Mandon-Pepin B, Evans N P, Sharpe R M
Institute of Biodiversity, Animal Health and Comparative Medicine, School of Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, UK.
Int J Androl. 2012 Jun;35(3):317-29. doi: 10.1111/j.1365-2605.2011.01234.x. Epub 2011 Dec 13.
Exposure to ubiquitous, environmental chemicals (ECs) has been hypothesized as a cause for declining male reproductive health. Understanding the long-term effects of EC exposure on reproductive health in humans requires animal models and exposure to 'real life', environmentally relevant, mixtures during development, a life stage of particular sensitivity to ECs. The aim of this study was to evaluate the effects of in utero and post-natal exposure to environmentally relevant levels of ECs, via sewage sludge application to pasture, on the adult male sheep testis. Hormones, liver concentrations of candidate ECs and Sertoli and germ cell numbers in testes of adult rams that were exposed to ECs in sewage sludge in utero, and until weaning via maternal exposure, and post-weaning via grazing pastures fertilized with sewage sludge, were quantified. Evaluated as a single group, exposure to sludge ECs was without significant effect on most parameters. However, a more detailed study revealed that 5 of 12 sludge-exposed rams exhibited major spermatogenic abnormalities. These consisted of major reductions in germ cell numbers per testis or per Sertoli cell and more Sertoli cell-only tubules, when compared with controls, which did not show any such changes. The sludge-related spermatogenic changes in the five affected animals were significantly different from controls (p < 0.001); Sertoli cell number was unaffected. Hormone profiles and liver candidate EC concentrations were not measurably affected by exposure. We conclude that developmental exposure of male sheep to real-world mixtures of ECs can result in major reduction in germ cell numbers, indicative of impaired sperm production, in a proportion of exposed males. The individual-specific effects are presumed to reflect EC effects on a heterogeneous population in which some individuals may be more susceptible to adverse EC effects. Such effects of EC exposure in humans could have adverse consequences for sperm counts and fertility in some exposed males.
普遍存在的环境化学物质(ECs)暴露被认为是男性生殖健康下降的一个原因。要了解ECs暴露对人类生殖健康的长期影响,需要动物模型,并在发育期间(对ECs特别敏感的生命阶段)让其暴露于“现实生活中”与环境相关的混合物中。本研究的目的是评估通过将污水污泥施用于牧场,在子宫内和出生后暴露于与环境相关水平的ECs对成年雄性绵羊睾丸的影响。对成年公羊的激素、肝脏中候选ECs的浓度以及睾丸中的支持细胞和生殖细胞数量进行了量化,这些公羊在子宫内通过母体暴露于污水污泥中的ECs,直至断奶,断奶后通过食用用污水污泥施肥的牧场继续暴露。作为一个单一组进行评估时,暴露于污泥ECs对大多数参数没有显著影响。然而,一项更详细的研究表明,12只暴露于污泥的公羊中有5只表现出严重的生精异常。与对照组相比,这些异常包括每个睾丸或每个支持细胞中的生殖细胞数量大幅减少,以及更多仅含支持细胞的小管,而对照组未出现任何此类变化。五只受影响动物中与污泥相关的生精变化与对照组有显著差异(p < 0.001);支持细胞数量未受影响。激素水平和肝脏中候选ECs的浓度未因暴露而受到可测量的影响。我们得出结论,雄性绵羊在发育过程中暴露于现实世界中的ECs混合物可导致一部分暴露雄性的生殖细胞数量大幅减少,这表明精子生成受损。个体特异性效应被认为反映了ECs对异质群体的影响,其中一些个体可能对ECs的不利影响更敏感。ECs暴露对人类的这种影响可能会对一些暴露男性的精子数量和生育能力产生不利后果。