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Human Reproduction, Vol. 18, No. 3, 576-582, March 2003
© 2003 European Society of Human Reproduction and Embryology

Abnormal assembly of annulate lamellae and nuclear pore complexes coincides with fertilization arrest at the pronuclear stage of human zygotic development

V.Y. Rawe1,4, S.Brugo Olmedo1, F.N. Nodar1, R. Ponzio2 and P. Sutovsky3

1 Centro de Estudios en Ginecología y Reproducción, CEGyR, Buenos Aires, 2 Centro de Investigaciones en Reproducción, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina and 3 Departments of Obstetrics and Gynecology, and Animal Science, University of Missouri–Columbia, S141 ASRC, 920 E Campus Drive, Columbia, MO 65211–5300, USA

4 To whom correspondence should be addressed at: Pittsburgh Developmental Center of Magee–Women’s Research Institute and Departments of Obstetrics–Gynecology–Reproductive Sciences and Cell Biology and Physiology, University of Pittsburgh, 204 Craft Ave, Pittsburgh, PA 15213, USA. e-mail: vrawe@mail.magee.edu

BACKGROUND: The assembly of nuclear pore complexes (NPC) and their cytoplasmic stacks, annulate lamellae (AL), promote normal nucleocytoplasmic trafficking and accompany pronuclear development within the mammalian zygote. Previous studies showed that a percentage of human oocytes fertilized in vitro failed to develop normal pronuclei and cleave within 40–48 h post insemination. We hypothesized that an aberrant recruitment of NPC proteins, nucleoporins and/or NPC preassembled into AL, might accompany human fertilization arrest. METHODS AND RESULTS: We explored NPC and AL assembly in unfertilized human oocytes, and fertilized and arrested zygotes by immunofluorescence with an NPC- and AL-specific antibody, mAb 414, and by transmission electron microscopy. Major NPC or AL assembly was not observed in the unfertilized human oocytes. Once fertilization took place, the formation of AL was observed throughout the cytoplasm and near the developing pronuclei with NPC. On the contrary, NPC assembly was disrupted in the arrested zygotes, whereas AL were clustered into large sheaths. This was accompanied by the lack of NPC incorporation into the nuclear envelopes. CONCLUSIONS: We conclude that the aberrant assembly of NPC and AL coincides with early developmental failure in humans.

Key words: fertilization failure/human zygotes/nuclear envelope/nuclear pore complex/pronuclear development


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