PMID- 15987647
OWN - NLM
STAT- MEDLINE
DCOM- 20081001
LR  - 20050912
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 207
IP  - 2 Suppl
DP  - 2005 Sep 1
TI  - Environmental toxicants cause sperm DNA fragmentation as detected by the Sperm 
      Chromatin Structure Assay (SCSA).
PG  - 532-7
AB  - Studies over the past two decades have clearly shown that reproductive toxicants 
      cause sperm DNA fragmentation. This DNA fragmentation can usually be detected 
      prior to observing alterations of metaphase chromosomes in embryos. Thus, Sperm 
      Chromatin Structure Assay (SCSA)-detected DNA damage is viewed as the molecular 
      precursor to later gross chromosome damage observed under the light microscope. 
      SCSA measurements of animal or human sperm consist of first obtaining a fresh or 
      flash frozen neat semen sample in LN2 or dry ice. Samples are then sent to a SCSA 
      diagnostic laboratory where the samples are thawed, diluted to approximately 1-2 
      x 106 sperm/ml, treated for 30 s with a pH 1.2 detergent buffer and then stained 
      with acridine orange (AO). The low pH partially denatures DNA at the sites of DNA 
      strand breaks and the AO-ssDNA fluoresces red while the AO-dsDNA fluoresces 
      green. Flow cytometry measurements of 5000 sperm/sample provide statistically 
      robust data on the ratio of red to green sperm, the extent of the DNA 
      fragmentation and the standard deviations of measures. Numerous experiments on 
      rodents treated with reproductive toxicants clearly showed that SCSA measures are 
      highly dose responsive and have a very low CV. Different agents that act on germ 
      cells at various stages of development usually showed sperm DNA fragmentation 
      when that germ cell fraction arrived in the epididymis or ejaculate. Some of 
      these treated samples were capable of successful in vitro fertilization but with 
      frequent embryo failure. A 2-year longitudinal study of men living a valley town 
      with a reported abnormal level of infertility and spontaneous miscarriages and 
      also a seasonal atmospheric smog pollution, showed, for the first time, that SCSA 
      measurements of human sperm DNA fragmentation were detectable and correlated with 
      dosage of air pollution while the classical semen measures were not correlated. 
      Also, young men spraying pesticides without protective gear are at an increased 
      risk for elevated sperm DNA fragmentation. Extensive DNA fragmentation probably 
      cannot be repaired by the egg and the spontaneous abortion rate is approximately 
      2x higher if a man has more than 30% of sperm showing DNA fragmentation. DNA 
      fragmentation is an excellent marker for exposure to potential reproductive 
      toxicants and a diagnostic/prognostic tool for potential male infertility.
FAU - Evenson, Donald P
AU  - Evenson DP
AD  - HCLD, Department of Chemistry and Biochemistry, South Dakota State University, 
      Brookings, SD 57007, USA. scsa@brookings.net
FAU - Wixon, Regina
AU  - Wixon R
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Chromatin)
RN  - 0 (Environmental Pollutants)
SB  - IM
MH  - Chromatin/*chemistry
MH  - DNA Fragmentation/*drug effects
MH  - Environmental Pollutants/*toxicity
MH  - Humans
MH  - Infertility, Male/chemically induced
MH  - Longitudinal Studies
MH  - Male
MH  - Protein Conformation
MH  - Spermatozoa/*drug effects/metabolism/ultrastructure
RF  - 31
EDAT- 2005/07/01 09:00
MHDA- 2008/10/02 09:00
CRDT- 2005/07/01 09:00
PHST- 2004/07/15 00:00 [received]
PHST- 2005/03/10 00:00 [revised]
PHST- 2005/03/13 00:00 [accepted]
PHST- 2005/07/01 09:00 [pubmed]
PHST- 2008/10/02 09:00 [medline]
PHST- 2005/07/01 09:00 [entrez]
AID - S0041-008X(05)00241-3 [pii]
AID - 10.1016/j.taap.2005.03.021 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2005 Sep 1;207(2 Suppl):532-7. doi: 
      10.1016/j.taap.2005.03.021.