Effects of ooplasm transfer on paternal genome function in mice

Abstract

The ooplasm plays a central role in forming the paternal pronucleus, and subsequently in regulating the expression of paternally inherited chromosomes. Previous studies in mice have revealed genetic differences in paternal genome processing by ooplasm of different genotypes. Ooplasm donation coupled to intracytoplasmic sperm injection (ICSI) has been used in human assisted reproductive technology (ART). This procedure exposes the developing paternal pronucleus to 'foreign' ooplasm, which may direct aberrant epigenetic processing. The potential effects of the foreign ooplasm on epigenetic information in the paternal pronucleus are unknown; however, some human progeny from ooplasm donation procedures display abnormalities. In this study, we employed inter-genotype ooplasm transfer followed by ICSI using two mouse strains, C57BL/6 and DBA/2, to explore the influence of foreign ooplasm on paternal pronucleus function. In order to assay for effects on the paternal genome without masking effects of the maternal genome, we examined ooplasm effects in diploid androgenones, which are produced by pronuclear transfer to contain exclusively two paternal sets of chromosomes, in combination with ICSI. There was no significant effect of intra-strain ooplasm transfer among androgenones made with either C57BL/6 or DBA/2 oocytes. There was a significant negative effect on androgenone blastocyst development with inter-genotype transfer (10% volume) of DBA/2 ooplasm to C57BL/6 oocytes (P < 0.05). The reciprocal inter-genotype ooplasm transfer had no significant effect. Thus, inter-genotype ooplasm transfer in conjunction with ICSI can alter the function of the paternal genome. However, the effect of foreign ooplasm is restricted to a negative effect, with no evidence of a positive effect. This study provides important new information about the possible consequences of ooplasm donation in human ART.