The interactions between oocyte and sperm or between ooplasm and the paternal genome that support early development remain poorly understood. We have discovered an interaction between oocyte and sperm that affects cellular integrity in the 2-cell mouse embryo. Cellular fragmentation and apoptosis during the preimplantation period of development have been observed in a variety of species, including human, mouse, and bovine, but this process is poorly understood. Blastomere fragmentation and apoptosis diminish fertility and may negatively affect the success rates of in vitro methods for treating infertility in humans. We have shown that the genotypes of both the mother and the father affect the incidence of fragmentation. Moreover, a significant parental origin effect is observed for reciprocal F1 hybrid mothers. This may reflect a strain difference in mitochondria or the involvement of at least one imprinted gene in controlling early blastomere fragmentation. Our data also reveal that the magnitude of the effect exerted by both maternal and paternal genotype are each dependent upon the genotype of the other. These observations establish a novel experimental system with which to examine the fundamental biological mechanisms that operate in embryos to maintain cellular integrity. Our findings also have important implications for human reproductive medicine, because they indicate that parameters of gamete fitness, particularly oocyte quality, or genetic factors affecting early development, cannot necessarily be evaluated independently of the genotype of the opposite parent. We propose to (a) determine whether maternal and paternal genotypes affect fragmentation through cytoplasmic constituents of the gametes or through allelic differences in genes expressed in the early embryo, (b) determine whether blastomere fragmentation at the 2-cell stage reflects activation of apoptotic processes or is the result of other aberrant cellular events, and (c) determine the long-term effects of partial blastomere fragmentation on embryo developmental competence. The proposed studies, when completed, should provide essential and valuable new information about the basic biology of the early embryo, oocyte-sperm interactions and their consequences, the roles of gamete-derived factors in controlling early embryo viability, and useful information for improving assisted reproduction techniques or for devising novel approaches to contraception. They should also provide the necessary cellular information with which to design biochemical, or genetic approaches to the identification of molecules involved in fragmentation. Last, because studies such as those proposed cannot be conducted in the human, the proposed studies will provide unprecedented data regarding the relationship between fragmentation and viability.
| Mtango, Namdori R; Sutovsky, Miriam; Vandevoort, Catherine A et al. (2012) Essential role of ubiquitin C-terminal hydrolases UCHL1 and UCHL3 in mammalian oocyte maturation. J Cell Physiol 227:2022-9 |
| Mtango, Namdori R; Sutovsky, Miriam; Susor, Andrej et al. (2012) Essential role of maternal UCHL1 and UCHL3 in fertilization and preimplantation embryo development. J Cell Physiol 227:1592-603 |
| Han, Zhiming; Mtango, Namdori R; Zhong, Zhisheng et al. (2010) Early transcription from the maternal genome controlling blastomere integrity in mouse two-cell-stage embryos. Am J Physiol Cell Physiol 298:C1235-44 |
| Liang, Cheng-Guang; Han, Zhiming; Cheng, Yong et al. (2009) Effects of ooplasm transfer on paternal genome function in mice. Hum Reprod 24:2718-28 |
| Cheng, Yong; Wang, Kai; Kellam, Lori D et al. (2009) Effects of ooplasm manipulation on DNA methylation and growth of progeny in mice. Biol Reprod 80:464-72 |
| Hao, Lanping; Vassena, Rita; Wu, Guangming et al. (2009) The unfolded protein response contributes to preimplantation mouse embryo death in the DDK syndrome. Biol Reprod 80:944-53 |
| Han, Zhiming; Mtango, Namdori R; Patel, Bela G et al. (2008) Hybrid vigor and transgenerational epigenetic effects on early mouse embryo phenotype. Biol Reprod 79:638-48 |
| Kuzmin, Anastasia; Han, Zhiming; Golding, Michael C et al. (2008) The PcG gene Sfmbt2 is paternally expressed in extraembryonic tissues. Gene Expr Patterns 8:107-16 |
| Mtango, Namdori R; Potireddy, Santhi; Latham, Keith E (2008) Oocyte quality and maternal control of development. Int Rev Cell Mol Biol 268:223-90 |
| Han, Zhiming; Chung, Young Gie; Gao, Shaorong et al. (2005) Maternal factors controlling blastomere fragmentation in early mouse embryos. Biol Reprod 72:612-8 |
