Paternal Influence on Developmental Toxicity Following Administration of Therapeutic Drugs and Direct Impact on Developmental Toxicity

Abstract

In the last few decades, a new concept of developmental origins of health and disease was introduced based upon the paternal contribution to developmental toxicity. This was attributed to the first reports on the incidence of leukemia in children whose parents worked at Sellafield Nuclear Plant in West Cumbria, England, which created awareness to the scientific community to the possibility of male-mediated developmental toxicity. Thus, animal studies commenced, which demonstrated that genetic damage to paternal DNA following exposure to radiation or chemical products (mutagens) may be transmitted to the offspring. Several studies highlighted the paternal impact on the development of toxicity following exposure to endocrine disruptors, alcohol, nicotine, radiation as well as antineoplastic drugs, but other factors including environmental factors, social factors, and chemicals that men are also exposed to might also directly influence sperm quality, resulting in DNA damage and consequently affecting the development of offspring, which have not yet received much attention. In this chapter, paternal exposure to various risk factors including obesity, stress, anxiety, and medications used to treat several conditions, such as anxiolytics, antidepressants, glucocorticoids, anorexigens, antirheumatics, antiepileptics and analgesic drugs, is described with associated potential impact on the development of offspring toxicity. Even though many studies still need to be carried out, it is known that spermatozoa might constitute one of the crucial keys in the development of health or disease of the offspring.