Figure 2: The unique architecture of spermatozoa infl uences the impact of apoptosis on DNA integrity. (a) Conventional somatic cells feature a centrally placed nucleus surrounded by mitochondria embedded in the cytoplasm. Under these circumstances, endonucleases activated in the cytoplasm or released from the mitochondria during apoptosis are able to move into the nucleus (arrows) and cleave the DNA. (b) Spermatozoa are completely different from such somatic cells because their mitochondria (stained black) and most of their cytoplasm are located in the midpiece of the cell, physically separated from the nucleus. (c) As a consequence of this compartmentalization key effectors of apoptosis such as apoptosis inducing factor (AIF) or Endonuclease G (Endo G) remain resolutely locked in the sperm midpiece even when apoptosis is induced by the powerful PI3 kinase inhibitor, wortmannin and cannot move into the sperm nucleus. Because of this physical limitation, most DNA damage in mature spermatozoa is induced by membrane permeant reactive oxygen species emanating from the mitochondria, rather than nucleases.