Laboratory methods for the detection of chromosomal structural aberrations in human and mouse sperm by fluorescence...

The father, like the mother, can transmit genetic defects that are detrimental for development and genetic health for his children, but the mechanisms for paternally mediated abnormal reproductive outcomes remain poorly understood. A battery of sensitive methods has been developed for detecting genetic damage associated with infertility, spontaneous abortions, as well as inherited defects in children such as aneuploidy syndromes, translocation carriers, and certain genetic diseases directly in sperm. Among these, fluorescence in situ hybridization (FISH) sperm-based assays for measuring numerical abnormalities and structural chromosomal aberrations are now available for an expanding number of species including humans, rodents, and several domesticated animals. This new generation of sperm FISH methods has identified several paternal risk factors such as age, various drugs, lifestyles, and various environmental and occupational exposures. These sperm FISH assays provide new opportunities to identify and characterize male reproductive risks associated with genetic, lifestyle, and environmental factors. This chapter outlines the laboratory methods for the detection of sperm with chromosomal structural aberrations in humans (ACM assay) and mice (CT8 assay) that have been validated for detecting environmental germ cell mutagens.