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Apoptosis is a highly regulated form of cell death, involving a cascade-like activation of a series of catabolic processes that progressively disassemble the cell. High levels of endogenous maternal estrogens are associated with increased risks of testicular cancer and cryptorchidism in male offspring. In males, smoking negatively affects sperm production, motility, and morphology. Enzymes involved in the steroid biosynthesis pathway are beginning to be recognized as targets for the action of a number of endocrine-disrupting chemicals (EDCs). The blood-testis barrier (BTB) serves to protect spermatogenesis from many potentially cytotoxic drugs and other chemicals. Drugs and medications may have an adverse impact on fertility through a variety of mechanisms including direct toxicity to the testicular germ cells and supporting cells, alterations of the hypothalamic-pituitary-gonadal (HPG) axis, or effects on sexual performance by impairment of libido, erections, or ejaculation.