Impaired embryogenesis following intracytoplasmic sperm injection with an Arrdc5-/- mouse model of oligoasthenoteratospermia†.

Abstract

Oligoasthenoteratospermia (OAT) describes male infertility due to a combination of low sperm count, reduced sperm motility, and abnormal sperm morphology. A common course of action to overcome infertility for males with this condition is intracytoplasmic sperm injection (ICSI). Here we used the Arrdc5 knockout mouse model of OAT to examine the ramifications of bypassing natural barriers preventing fertilization by defective sperm via ICSI on the viability of embryos and health of offspring. ARRDC5 is expressed specifically in the male germline where it has an essential role in sperm morphogenesis and is required for normal embryogenesis. Outcomes of ICSI trials with sperm from Arrdc5-/- males and wild-type oocytes revealed that the efficacy of both 2-cell and blastocyst stage embryo generation is significantly compromised. In addition, forcing increased embryo development by inclusion of artificial oocyte activation enabled the generation of a viable pregnancy from ICSI with Arrdc5-/- sperm, however, the live Arrdc5+/- offspring that was generated had organ wet weights outside of the range of Arrdc5+/+ mice generated by ICSI with sperm from Arrdc5+/+ males. Moreover, evidence of DNA damage transmission to paternal pronuclei following ICSI with sperm from Arrdc5-/- mice was uncovered, though this DNA damage may resolve by the 2-cell stage of embryo development. Collectively, these findings demonstrate that both oocyte activation and post-cleavage preimplantation embryo development are impaired following ICSI with sperm generated by mice with an OAT pathology.