Human Reproduction, Vol 13, 1864-1871, Copyright © 1998 by Oxford University Press
JP Twigg, DS Irvine and RJ Aitken
We present the first evidence that genetically damaged human spermatozoa
are able to form normal pronuclei in oocytes after intracytoplasmic sperm
injection (ICSI). The role of reactive oxygen species (ROS) as a cause of
chromatin and DNA damage is well recognized. The same class of molecule can
be found in the semen of males with severe infertility, who remained
infertile until the advent of ICSI. In this study we have investigated the
role of ROS in the induction of chromatin damage, DNA strand breakage and
the subsequent ability of spermatozoa to decondense and form pronuclei
after ICSI. Spermatozoa from normozoospermic men participating in our
research programme were exposed to oxidizing environments created by co-
incubation with hydrogen peroxide, reduced nicotinamide adenine
dinucleotide phosphate (NADPH) or activated white cells. The subsequent
ability of the spermatozoa to decondense in vitro was examined using
sequential incubations in EDTA, dithiothreitol and sodium dodecyl sulphate,
and the amounts of DNA strand breakage were assessed using an in-situ nick
translation protocol. Finally, cells exposed to hydrogen peroxide, NADPH
and activated leukocytes were microinjected into hamster oocytes, and their
ability to decondense and form normal pronuclei was determined. The results
indicate that human sperm chromatin becomes cross-linked under conditions
of oxidative stress and exhibits increased DNA strand breakage, yet the
rate of pronucleus formation is no different from that of untreated control
cells. The ability of genetically damaged spermatozoa to achieve normal
fertilization following ICSI has implications for the practice of this form
of assisted conception therapy.
ARTICLES
Oxidative damage to DNA in human spermatozoa does not preclude pronucleus formation at intracytoplasmic sperm injection
MRC Reproductive Biology Unit, Edinburgh.
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