Paternal DNA damage suppresses in vitro proliferation of mouse inner cell mass

Objective: Sperm DNA damage is known to cause developmental failure and reduction in the numbers of live offspring and the effects of damages range as diverse as embryonic death and cancer susceptibility in the offspring. Here we report the in vitro proliferation ability of the inner cell mass of the mouse embryos derived from the DNA damaged sperm and its association with post implantation developmental potential. Material and Method: Day 3.5 mouse embryos derived from the DNA damaged sperm were cultured on MEF feeder layer and proliferation ability of the inner cell mass was assessed for six days. The post implantation developmental competence was studied by fetoplacental analysis on day 18 of gestation. Results: The development of embryos derived from 6 Gy irradiated sperm demonstrated heterogeneous growth on day 3.5 as approximately 1/3rd of the embryos failed to undergo compaction and demonstrated high frequency of micronuclei. In addition embryos showing developmental delay on day 3.5 failed to form any outgrowth during 6 day of in vitro culture. The fetoplacental analysis on day 18 of gestation showed a 50% reduction in the number of fetus derived from the DNA damaged sperm although the number of implantations was not affected. Conclusions: Our study demonstrates that DNA damage in sperm can lead to preimplantation embryonic developmental delay resulting in defective ICM proliferation possibly due to increased genomic instability and such embryos die in utero.