ABSTRACT
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.
Subject(s)
Chromosome Aberrations , In Situ Hybridization, Fluorescence/methods , Spermatozoa/metabolism , Animals , Environmental Monitoring/methods , Hazardous Substances/toxicity , Humans , Male , Mice , Reproducibility of Results , Spermatozoa/drug effectsABSTRACT
OBJECTIVE: To investigate the association between male age and the frequency of sperm with de novo structural chromosomal abnormalities. DESIGN: Semen specimens collected from two groups of 10 healthy, nonsmoking men, aged 22-28 and 65-80 years, were analyzed with the use of a multicolor fluorescence in situ hybridization assay for detecting breaks, segmental duplications and deletions, and aneuploidy and diploidy involving chromosome 1. SETTING: Healthy volunteer workers and retirees from a government research environment. MAIN OUTCOME MEASURE: Sperm carrying numerical and structural chromosomal abnormalities. RESULT(S): We detected significant increases in the frequency of sperm carrying breaks and segmental duplications and deletions of chromosome 1 among older men compared with younger men. Older men carried twice the frequency of sperm with segmental duplications and deletions of chromosome 1. The frequency of sperm carrying breaks within the 1q12 fragile-site region nearly doubled in older men. In contrast to female gametes, there was no effect of age on the frequency of sperm with numerical chromosomal abnormalities. CONCLUSION: Our findings suggest that advancing male age is associated with a gradual and significant increase in the risk of fathering children with various chromosomal defects such as segmental aneusomy syndromes.
