September 7, 2002
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Study identifies genetic fingerprint of healthy sperm
The genetic fingerprinting of sperm cells—detailed in this week’s issue of
THE LANCET—could be a major step forward in our understanding of male infertility.
Around one in six couples experience difficulty in conceiving a child, and male
fertility problems account for half of assisted reproductive techniques. However,
the underlying cause of infertility is essentially unknown in about two-thirds of
infertile men who undergo infertility assessment.
Findings from several studies suggest that sperm cells have a complex genetic code
made up of components called messenger RNA (mRNA). Stephen Krawetz from Wayne State
University, Detroit, USA, David Miller from the University of Leeds, UK, and David Dix
from the Environmental Protection Agency, North Carolina, USA, investigated whether mRNAs
from sperm cells could be used to generate a genetic fingerprint of the sperm of fertile
men. The investigators used genetic mapping techniques to assess sperm mRNAs from 19
testes, a pool of sperm cells from nine individual ejaculates, and from sperm cells
from a single ejaculate.
Analysis of sperm cells in the study identified around 3000 individual mRNAs for
the fertile male. The investigators comment that this non-invasive ‘gold standard’
can be used in the future as a benchmark for comparisons of genetic analysis from
sperm of infertile men; future analysis should identify the defective genes that
contribute to infertility. Furthermore, the investigators suggest that some of the
mRNA in healthy sperm could contribute to the viability of the zygote after fertilisation.
Stephen Krawetz comments: “We have completed a genome-wide analysis to define the
spermatozoal RNA fingerprint of normal fertile men. By contrast with assessments of
semen quality that rely on subjective physiological and morphological criteria, the
methods outlined in this study provide a unique and objective opportunity to identify
and diagnose idiopathic infertilities with spermatozoal mRNA fingerprints. The
spermatozoal fingerprint of normal fertile men could help to elucidate the underlying
causes of male-factor infertility and begin to reveal why mRNAs remain in mature spermatozoa.”
In an accompanying Commentary (p 742), Gerald Schatten from the University of Pittsburgh
School of Medicine, USA, states: “Less than 3000 different mRNAs define fertile sperm…these
mRNAs may become invaluable for: new diagnostics for idiopathic infertility; discovering
paternal influences to both the fetus and the placenta; ascertaining if there are generational
consequences of environmental exposures of boys and men; new strategies for male
contraception…Are sperm mRNAs remnants of their past lives during spermatogenesis, especially
spermiogenesis, or vital packets essential to energise embryos? Such information is especially
important for its prognostic value when evaluating each sperm’s reproductive potential.”
Contact: Dr Stephen A Krawetz, Wayne State University School of Medicine, 253 CS Mott Center,
275 East Hancock, Detroit, MI 48201, USA; T) +1 313 577 6770; F) +1 313 577 8554; E)
steve@compbio.med.wayne.edu
Dr David Miller, c/o Abigail Chard, Press Office, University of Leeds, Leeds, LS2 9JT,
UK; T)+44 (0)113 343 6699; F) +44 (0)113 343 4125; E) a.chard@adm.leeds.ac.uk
David Dix, Research Biologist, Reproductive Toxicology Division (MD-72) National
Health and Environmental Effects Research Laboratory, US Environmental Protection Agency,
Research Triangle Park, NC 27711, UA; T) +1 919 541 2701; F) +1 919 541 4017; E) dix.david@epa.gov
Professor Gerald P Schatten, Department of Obstetrics, Gynecology, Reproductive Sciences,Cell Biology
and Physiology, University of Pittsburgh School of Medicine, Magee-Womens Research Institute,
204 Craft Avenue, Pittsburgh PA 15213, USA; T) +1 412 641 2400; F) +1 412 641 2410; E)
pdcgs@mail.magee.edu