Development to blastocyst is impaired when intracytoplasmic sperm injection is performed with abnormal sperm from infertile mice harboring a mutation in the protein phosphatase 1cgamma gene.
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 1cgamma gene (PP1cgamma) or those of their wild-type littermates. PP1cgamma 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. PP1cgamma 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.
Davies
Tyler
T
Department of Zoology, University of Toronto, Toronto, Ontario, Canada M5S 3G5.
Varmuza
Susannah
S
D000818:Animals; D001755:Blastocyst; D005314:Embryonic and Fetal Development; D004822:Epididymis; D006720:Homozygote; D007248:Infertility, Male / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D051379:Mice; D009154:Mutation; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D020554:Sperm Injections, Intracytoplasmic; D013094:Spermatozoa / Q000002:abnormalities*; D013737:Testis
D017346:Protein Serine-Threonine Kinases; D010749:Phosphoprotein Phosphatases; C517103:Ppp1cc protein, mouse; D054645:Protein Phosphatase 1