Abstract
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.
Highlights
It is established that exposure to certain environmental chemicals (ECs) at supra-environmental concentrations can have harmful effects on several physiological systems in animals and potentially in humans (Colborn et al., 1993; Langer et al, 1998; Vine et al, 2000)
Sertoli cells (SC) proliferate in perinatal life, which is critical because SC number determines the number of germ cells that can be supported through spermatogenesis, and determines the extent of sperm production in adulthood (Sharpe et al, 2003)
There was no significant difference in weight between left and right testes in individuals in either control or exposed rams
Summary
It is established that exposure to certain environmental chemicals (ECs) at supra-environmental concentrations can have harmful effects on several physiological systems in animals and potentially in humans (Colborn et al., 1993; Langer et al, 1998; Vine et al, 2000) Exposure to such ECs has been hypothesized to account for the high and ⁄ or increasing incidence of male reproductive disorders in humans, such as testicular germ cell cancer, cryptorchidism, hypospadias and some cases of low sperm counts. SCs are the first cells to differentiate in the indifferent gonad, an event which triggers seminiferous cord formation, prevention of germ cell entry into meiosis and differentiation and function of LCs (Mackay, 2000) The latter secrete testosterone and insulin like factor-3 (INSL3), which drive downstream masculinization events and testicular descent (Hutson et al, 1997; Sharpe, 2001). Given the fundamental role of SCs in testis development and spermatogenesis, altered SC proliferation or functional development in perinatal life will probably have consequences for adult reproductive function and fertility (Skakkebaek et al, 2001a,b; Sharpe, 2010)
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