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Human Reproduction, Vol. 13, No. suppl_4, pp. 11-19, 1998
© 1998 European Society of Human Reproduction and Embryology

Sperm nuclear DNA damage and altered chromatin structure: effect on fertilization and embryo development

D. Sakkas1,3, F. Urner1, D. Bizzaro2, G. Manicardi2, P.G. Bianchi1, Y. Shoukir1 and A. Campana1

1 Clinic of Infertility and Gynaecological Endocrinology-WHO Collaborating Centre in Human Reproduction, Department of Obstetrics and Gynaecology, University Hospital of Geneva Switzerland 2 Department of Animal Biology, University of Modena Via Berengario 14, 41100 Modena, Italy

Correspondence: 3To whom correspondence should be addressed at: Assisted Conception Unit, Birmingham Women's Hospital, Edgbaston, Birmingham B15 2TG, UK

In the first part of this report we investigate whether chromatin anomalies in human spermatozoa can influence fertilization after intracytoplasmic sperm injection (ICSI). We have examined the sperm chromatin packaging quality using the chromomycin A3 (CMA3) fluorochrome and the presence of DNA damage in spermatozoa using in-situ nick translation. When comparing the spermatozoa of patients undergoing in-vitro fertilization (IVF) and ICSI distinct differences are evident in that ICSI males have a higher CMA3 fluorescence, indicating spermatozoa with loosely packed chromatin, and more spermatozoa containing endogenous DNA nicks. When examining the unfertilized oocytes of ICSI patients we found that men who had a high percentage of anomalies in their chromatin, i.e. >30% CMA3 fluorescence and >10% nicks, had more than double the number of unfertilized oocytes containing spermatozoa that had remained condensed. The observation that failed fertilized oocytes, injected with spermatozoa from patients with a higher percentage of sperm nuclear anomalies, contain more condensed spermatozoa indicates that a selection process against these spermatozoa may be in place at the time of fertilization. In the second part of the study we show that spare ICSI embryos have significantly lower rates of development to the blastocyst stage compared with those developed after routine IVF. These results show that a greater understanding of the molecular basis of male infertility is therefore needed to broaden our knowledge on the effect that abnormal spermatozoa have on fertilization and embryo development.

Key words: fertilization/intracytoplasmic sperm injection/male infertility/sperm chromatin/sperm nuclear decondensation


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