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Development to Blastocyst Is Impaired When Intracytoplasmic Sperm Injection Is Performed with Abnormal Sperm from Infertile Mice Harboring a Mutation in the Protein Phosphatase 1c Gene¹

^a Department of Zoology, University of Toronto, Toronto, Ontario, Canada M5S 3G5

Idiopathic azoospermia, characterized by abnormal spermatogenesis, is commonly treated by performing intracytoplasmic sperm injection (ICSI) with sperm retrieved from testicular biopsies. However, no controlled experiments have been performed using an animal model to assess the efficacy or safety of the procedure. We have performed ICSI with testicular sperm obtained in a similar manner from testes of male mice homozygous for a null mutation in the protein phosphatase 1c gene (PP1c) or those of their wild-type littermates. PP1c mutant testicular sperm are less resistant to sonication than are wild-type sperm and display a range of morphological abnormalities, similar to those reported for testicular sperm from idiopathic azoospermic men. PP1c mutant sperm are unable to support development to the blastocyst stage, resulting in arrested development either before or just after compaction. A comparison of testicular and epididymal sperm from wild-type males revealed that the epididymal sperm caused embryos to fragment at an elevated rate. These results suggest that ICSI with any kind of testicular sperm carries an increased risk of embryo fragmentation and that abnormal testicular sperm has an added risk of embryo wastage at later preimplantation stages.

¹ Financial support for this work was provided by the Canadian Institutes of Health Research (to S.V.).

² Correspondence: Susannah Varmuza, Department of Zoology, University of Toronto, 25 Harboard St., Toronto, ON, Canada M5S 3G5. FAX: 416 978 8532; svarmuza{at}zoo.utoronto.ca

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