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Human Reproduction, Vol. 10, No. 7, pp. 1897-1906, 1995
© 1995 European Society of Human Reproduction and Embryology


research-article

Fertilization and development: The stages at which human fertilization arrests: microtubule and chromosome configurations in inseminated oocytes which failed to complete fertilization and development in humans

R. Asch1,4, C. Simerly2, T. Ord1, V.A. Ord1 and G. Schatten2,3

1Center for Reproductive Health, University of California, Irvine Medical Center 101 The City Drive, Orange, CA 92668 2Department of Zoology, University of Wisconsin 1117 West Johnson Street, Madison, WI 53706, USA 3Department of Obstetrics-Gynecology, University of Wisconsin 1117 West Johnson Street, Madison, WI 53706, USA

Correspondence: 4To whom correspondence should be addressed

The goal of fertilization is the union of one, and only one, sperm nucleus with the female pronucleus within the activated oocyte. For this to occur successfully, several events must transpire, including the incorporation of the entire spermatozoon into the oocyte, the completion of meiotic maturation with the extrusion of the second polar body, the metabolic activation of the previously quiescent oocyte, the decondensation of the sperm nucleus and the maternal chromosomes into the male and female pronuclei respectively, and the cytoplasmic migrations of the pronuclei, which bring them into apposition. Defects in any of these events are lethal to the zygote and might prove to be causes of infertility. In this study, the microtubules and DNA were imaged in inseminated human oocytes that had been discarded as unfertilized. The presence and number of incorporated sperm tails were also documented using a monoclonal antibody specific for the post-translationally modified acetylated-{alpha}-tubulin found in the tail, but not the oocyte, microtubules. An analysis of 211 oocytes from failed in-vitro fertilizations from 58 patient couples resulted in the determination of several previously undetectable phases at which fertilization arrests: (i) metaphase II arrest; (ii) arrest after the successful incorporation of the spermatozoon; (iii) arrest after the formation of the sperm aster; (iv) arrest during mitotic cell cycle progression; and (v) arrest during meiotic cell cycle progression. Data on polyspermy and arrested embryonic development are also presented. These results have implications for the diagnosis and treatment of female, as well as male, infertility. They also provide a rationale for the reasonable use of intracytoplasmic sperm injection (ICSI) therapy, although they suggest that cases intractable to this approach will be found. Concerns are raised about the use of seemingly 'unfertilized' but inseminated oocytes for subsequent re-inseminations, ICSI or even research, since the fertilization process might have arrested after sperm penetration. These results demonstrate that the proper union of the parental genomes requires a series of cytoskeletal-mediated events on the oocyte surface and within the oocyte proper, and that failure at any phase results in the arrest of human fertilization.

Key words: arrest/chromosomes/fertilization/human/microtubules


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