Unique checkpoints during the first cell cycle of fertilization after intracytoplasmic sperm injection in rhesus monkeys

Laura Hewitson, Tanja Dominko, Diana Takahashi, Crista Martinovich, Joao Ramalho-Santos, Peter Sutovsky, John Fanton, Darla Jacob, Daymond Monteith, Martha Neuringer, David Battaglia, Cal Simerly, Gerald Schatten

Research output: Contribution to journalArticle

180 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)431-433
Number of pages3
JournalNature medicine
Volume5
Issue number4
DOIs
StatePublished - Apr 1 1999

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Hewitson, L., Dominko, T., Takahashi, D., Martinovich, C., Ramalho-Santos, J., Sutovsky, P., Fanton, J., Jacob, D., Monteith, D., Neuringer, M., Battaglia, D., Simerly, C., & Schatten, G. (1999). Unique checkpoints during the first cell cycle of fertilization after intracytoplasmic sperm injection in rhesus monkeys. Nature medicine, 5(4), 431-433. https://doi.org/10.1038/7430