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Hum. Reprod. Advance Access originally published online on July 21, 2005
Human Reproduction 2005 20(11):3101-3108; doi:10.1093/humrep/dei169
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© The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org

Decline in fertility of mouse sperm with abnormal chromatin during epididymal passage as revealed by ICSI

Ryota Suganuma1,3, Ryuzo Yanagimachi1 and Marvin L. Meistrich2,4

1 Institute for Biogenesis Research, University of Hawaii Medical School, Honolulu, HI 96822 and 2 Department of Experimental Radiation Oncology, The University of Texas M.D.Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA 3 Present address: Department of Obstetrics and Gynecology, Fukushima Medical University, Fukushima, Japan 960-1295

4 To whom correspondence should be addressed: E-mail: meistrich{at}mdanderson.org

BACKGROUND: Recent studies showed that ICSI with cauda epididymal or ejaculated sperm of infertile mice or men, respectively, was less effective in fertilization and normal embryo development than ICSI using sperm from the testes. These studies suggested that sperm nuclear quality declined after release from the testis, but the site where this loss of fertility occurs has not been localized. METHODS: We performed ICSI with testicular, caput, and cauda epididymal sperm from infertile Tnp1–/–Tnp2+/– mutant mice, which have a minimal level of transition nuclear proteins and are sterile by natural mating. RESULTS: When the heads of motile sperm from the testis or caput epididymis of Tnp1–/–Tnp2+/– males were injected into enucleated mouse oocytes, sperm chromosomes showed no difference from those of wild-type mice, but the chromosomes from sperm taken from the cauda epididymis of mutant males showed increased abnormalities. Injection of testicular or caput epididymal sperm from Tnp1–/–Tnp2+/– males into intact oocytes resulted in normal embryonic and fetal development and yields of liveborn equivalent to wild-type, but cauda sperm from Tnp1–/–Tnp2–/– mice produced lower implantation rates and yields of liveborn than did those from wild-type mice. CONCLUSIONS: These results demonstrate that in mice with sperm chromatin abnormalities, the decline in fertility of sperm with ICSI occurs after the caput epididymis. The advantage of using caput epididymal sperm for ICSI in certain situations may be considered as an approach to be tested in human assisted reproduction.

Key words: embryo development/epididymal sperm/ICSI/testicular sperm/transition nuclear proteins


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