Reproductive Technology

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 Gene

Abstract

Idiopathic azoospermia, characterized by abnormal spermatogenesis, is commonly treated by performing ICSI with sperm retrieved from testicular biopsies. 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 mouse testes that are derived from males homozygous for a null mutation in the Protein phosphatase 1c gene (PP1c), or their wild type littermates. PP1c mutant testicular sperm are less resistant to sonication than 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, causing arrest either before or just after compaction. We have also compared testicular and epididymal sperm from wild type males, and find that the latter cause embryos to fragment at an elevated rate. Our experiments 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. We suggest experiments to further our understanding of these defects.