TY - JOUR
T1 - Unique checkpoints during the first cell cycle of fertilization after intracytoplasmic sperm injection in rhesus monkeys
AU - Hewitson, Laura
AU - Dominko, Tanja
AU - Takahashi, Diana
AU - Martinovich, Crista
AU - Ramalho-Santos, Joao
AU - Sutovsky, Peter
AU - Fanton, John
AU - Jacob, Darla
AU - Monteith, Daymond
AU - Neuringer, Martha
AU - Battaglia, David
AU - Simerly, Cal
AU - Schatten, Gerald
N1 - Funding Information:
Acknowledgments We are grateful to P. Kirk and K. Burry at Oregon Health Sciences University; S. Smith at the Oregon Regional Primate Research Center; D. Hess for hormone analyses; S. Siemon, D. Ediger, K. Grund, K. Mueller and T. Swanson for animal husbandry; M. Emme for administrative assistance and C. Payne for his trigonometric expertise. We thank D. Compton (Dartmouth College), P. de Lanerolle (University of Illinois at Chicago), R. Oko (Queen’s University, Kingston, Ontario, Canada), M. Soules (University of Washington, Seattle), G. Wessel (Brown University), Serono (Randolph, Massachusetts) and Organon (West Orange, New Jersey). This research was supported by the National Institutes of Health (NICHD and NCRR, G.S.), the Foundation Fighting Blindness (M.N.) and the Portuguese Foundation for Science and Technology (FCT) and the Luso-American Development Foundation (FLAD; J.R.-S.). Studies on clinically discarded human oocytes were supported by non-federal sources. These protocols were approved by the responsible Human Subjects Institution Review Boards (IRB) and Institutional Animal Care and Use Committee (IACUC).
PY - 1999/4
Y1 - 1999/4
N2 - Intracytoplasmic sperm injection has begun an era of considerable improvements in treating male infertility. Despite its success, questions remain about the dangers of transmitting traits responsible for male infertility, sex and autosomal chromosome aberrations and possible mental, physical and reproductive abnormalities. We report here the first births of rhesus monkeys produced by intracytoplasmic sperm injection at rates greater or equal to those reported by clinics. Essential assumptions about this process are flawed, as shown by results with the preclinical, nonhuman primate model and with clinically discarded specimens. Dynamic imaging demonstrated the variable position of the second meiotic spindle in relation to the first polar body; consequently, microinjection targeting is imprecise and potentially lethal. Intracytoplasmic sperm injection resulted in abnormal sperm decondensation, with the unusual retention of vesicle-associated membrane protein and the perinuclear theca, and the exclusion of the nuclear mitotic apparatus from the decondensing sperm nuclear apex. Male pronuclear remodeling in the injected oocytes was required before replication of either parental genome, indicating a unique G1-to-S transition checkpoint during zygotic interphase (the first cell cycle). These irregularities indicate that the intracytoplasmic sperm injection itself might lead to the observed increased chromosome anomalies.
AB - Intracytoplasmic sperm injection has begun an era of considerable improvements in treating male infertility. Despite its success, questions remain about the dangers of transmitting traits responsible for male infertility, sex and autosomal chromosome aberrations and possible mental, physical and reproductive abnormalities. We report here the first births of rhesus monkeys produced by intracytoplasmic sperm injection at rates greater or equal to those reported by clinics. Essential assumptions about this process are flawed, as shown by results with the preclinical, nonhuman primate model and with clinically discarded specimens. Dynamic imaging demonstrated the variable position of the second meiotic spindle in relation to the first polar body; consequently, microinjection targeting is imprecise and potentially lethal. Intracytoplasmic sperm injection resulted in abnormal sperm decondensation, with the unusual retention of vesicle-associated membrane protein and the perinuclear theca, and the exclusion of the nuclear mitotic apparatus from the decondensing sperm nuclear apex. Male pronuclear remodeling in the injected oocytes was required before replication of either parental genome, indicating a unique G1-to-S transition checkpoint during zygotic interphase (the first cell cycle). These irregularities indicate that the intracytoplasmic sperm injection itself might lead to the observed increased chromosome anomalies.
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U2 - 10.1038/7430
DO - 10.1038/7430
M3 - Article
C2 - 10202934
AN - SCOPUS:0032957381
SN - 1078-8956
VL - 5
SP - 431
EP - 433
JO - Nature medicine
JF - Nature medicine
IS - 4
ER -