Origin of DNA damage in ejaculated human spermatozoa.
The molecular basis of many forms of male infertility is poorly defined. One area of research that has been studied intensely is the integrity of the DNA in the nucleus of mature ejaculated spermatozoa. It has been shown that, in men with abnormal sperm parameters, the DNA is more likely to possess strand breaks. However, how and why this DNA damage originates in certain males and how it may influence the genetic project of a mature spermatozoon is unknown. Two theories have been proposed to describe the origin of this DNA damage in mature spermatozoa. The first arises from studies performed in animal models and is linked to the unique manner in which mammalian sperm chromatin is packaged, while the second attributes the nuclear DNA damage in mature spermatozoa to apoptosis. One of the factors implicated in sperm apoptosis is the cell surface protein, Fas. In this review, we discuss the possible origins of DNA damage in ejaculated human spermatozoa, how these spermatozoa arrive in the ejaculate of some men, and what consequences they may have if they succeed in their genetic project.
Assisted Conception Unit, Birmingham Women's Hospital, Birmingham, UK.
D
D
Sakkas
E
E
Mariethoz
G
G
Manicardi
D
D
Bizzaro
P G
PG
Bianchi
U
U
Bianchi
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002869:Chromosome Aberrations / Q000235:genetics; D025063:Chromosome Disorders; D053938:DNA Fragmentation / Q000235:genetics* / Q000502:physiology; D004542:Ejaculation / Q000235:genetics / Q000502:physiology; D053222:Fas Ligand Protein; D005307:Fertilization in Vitro; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D051381:Rats; D012728:Sex Chromatin / Q000235:genetics / Q000502:physiology; D013094:Spermatozoa / Q000502:physiology*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins