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

Intracytoplasmic sperm injection has begun an era of considerable improveme nts in treating male infertility. Despite its success, questions remain abo ut the dangers of transmitting traits responsible for male infertility, sex and autosomal chromosome aberrations' and possible mental, physical and re productive abnormalities(2,3). We report here the first births of rhesus mo nkeys produced by intracytoplasmic sperm injection at rates greater or equa l to those reported by clinics. Essential assumptions about this process ar e flawed, as shown by results with the preclinical, nonhuman primate model and with clinically discarded specimens. Dynamic imaging demonstrated the v ariable position of the second meiotic spindle in relation to the first pol ar body; consequently, microinjection targeting is imprecise and potentiall y lethal. Intracytoplasmic sperm injection resulted in abnormal sperm decon densation, with the unusual retention of vesicle-associated membrane protei n and the perinuclear theca, and the exclusion of the nuclear mitotic appar atus from the decondensing sperm nuclear apex. Male pronuclear remodeling i n the injected oocytes was required before replication of either parental g enome, indicating a unique G(1)-to-S transition checkpoint during zygotic i nterphase (the first cell cycle). These irregularities indicate that the in tracytoplasmic sperm injection itself might lead to the observed increased chromosome anomalies(4-5).