Edinburgh Napier University

  Reproduction is the only certain constant within animals and maintaining the integrity of this process is key to ensuring survival of the species. However, male fertility rates in the Western world are in decline and the use of assisted reproductive techniques rising (Makarow and Hojgaard, 2010). With emerging technologies such as nanotechnologies presenting both enormous benefits alongside new risks, there is a clear need to understand and manage these potential novel threats to male reproductive health. However, the animal burden associated with such research is extreme, therefore consideration of how to reduce, refine or replace animal use in the associated developmental and reproductive toxicity (DART) testing is paramount.

This research aimed to assess the toxicity of engineered nanomaterials (ENM) in the male reproductive system and develop an improved testing strategy for hazard assessment of DART. Using a panel of highly representative ENM, assays to screen for toxicity in male testicular cell lines were established and optimised in vitro. Findings were then validated for reliability and reproducibility against those generated using similar test systems with cells from alternative organs of the body. Assessment of cell and endocrine function also provided a deeper understanding of cellular responses following acute sub-lethal ENM exposure.

Comparison of outcomes in vitro to in vivo was enabled by appraisal of tissues from animals exposed orally to the same ENM. Through this, a new method by which to stage tubules for histopathological analysis was developed, and for the first time a truly thorough morphological and stereological examination of tissues for markers of effect provided. Assimilation of key findings made it possible to conclude that silver ENM are reproductive toxicants and potential endocrine disruptors. The accumulated results were also used to guide development of a novel Integrated Approach to Testing and Assessment (IATA) for male reproductive toxicity from ENM.