Downregulation of gene expression and the outcome of ICSI in severe oligozoospermic patients: A preliminary study.

Abstract

Preimplantation embryo development might be influenced by a specific set of transcripts that are delivered to the oocyte by the sperm. The aim of the study was to determine the relationship between the level of selected transcripts in spermatozoa and preimplantation development of the embryos in couples with severe oligozoospermia undergoing intracytoplasmic sperm injection (ICSI) procedure. Therefore, we assessed messenger RNA (mRNA) levels of genes involved in fertilization events, oocyte activation, chromatin remodeling, and DNA repair in severe oligozoospermic compared with normozoospermic men as well as morphokinetic parameters of embryos using the time-lapse imaging system. mRNA profiling (44 genes), in mature sperm, was carried out with custom-designed 384-well TLDA Cards. The morphokinetic parameters of zygotes and embryos were recorded by using a time-lapse imaging system. The transcript levels of 21 genes were significantly decreased in the severe oligozoospermic group. Most were associated with fertilization events, oocyte activation and embryonic genome activation. Among them, mRNA of AKAP4 and PTK7 was greatly reduced, moreover, the transcripts of PLCζ and POU5F1, essential for OA and EGA, were not detected at all in patients with severe oligozoospermia. Moreover, the reduced expression of genes important for spermatogenesis, chromatin remodeling and DNA repair was also observed in this group. Time-lapse analysis revealed that fertilization failure occurred in 14% of retrieved oocytes and 90% of all degenerated embryos did not reach morula stage. This study provides preliminary results indicating a significant decrease in transcripts of genes important for spermatogenesis and early preimplantation development in the mature sperm of men with severe oligozoospermia.