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When a somatic cell nucleus is transplanted into an egg or an oocyte, the transplanted nucleus can be reprogrammed to support early embryonic development so that the reconstructed embryo gives rise to a cloned animal. Nuclear reprogramming of somatic nuclei is induced by maternal components stored in eggs and oocytes. These endogenous reprogramming factors and mechanisms have been explored for decades in mammals and amphibia. There are several ways of investigating reprogramming mechanisms, including nuclear transfer to eggs/oocytes and incubation in egg/oocyte extracts. In this review I describe the type of reprogramming events induced in each system and what factors in eggs and oocytes are responsible for these. Based on our current knowledge, I propose a model for the early phase of nuclear reprogramming in eggs and oocytes.
During the maternal-to-zygotic transition (MZT), maternal proteins in oocytes are degraded by the ubiquitin-proteasome system (UPS), which is first event after fertilization, and new proteins are then synthesized from the zygotic genome. Although degradation of accumulated maternal protein is essential for normal early embryonic development, the specific mechanisms underlying the UPS at the MZT are not well understood. We recently provided evidence that proteasomal degradation of maternal proteins is important for the onset of zygotic gene activation (ZGA), and that the zygote-specific proteasome assembly chaperone (ZPAC) plays an important role in the degradation of maternal proteins during mouse MZT. Here, we review why the degradation of maternal proteins via UPS is essential for embryonic reprogramming of the oocyte into a totipotent zygote that is makes somatic development possible.
During oogenesis, the oocyte stores a large amount of maternally provided products, including mRNAs and proteins. However, after fertilization, these products are rapidly degraded and new materials are synthesized from the zygotic genome. This oocyte-to-embryo transition, also known as the maternal-to-zygotic transition, is conserved in many species and plays a pivotal role in development, because non-degraded products can hamper further embryonic development. Given that the time of early embryonic development is so rapid, ubiquitin/proteasome-mediated turnover of individual proteins is probably not sufficient to remove maternal products during the oocyte-to-embryo transition. Autophagy is an evolutionally conserved degradation system in which portions of the cytoplasm sequestered by double membrane structures called autophagosomes are delivered to lysosomes for degradation. The basic roles of autophagy are the generation of amino acids for energy and the maintenance of cellular quality. In addition to the fundamental functions of autophagy, the unique role of autophagy in removing random cytoplasmic contents including mitochondria, peroxisomes, and even lipids, may contribute to extensive cellular remodeling during the oocyte-to-embryo transition. Here we briefly review the history and molecular mechanisms of autophagy, and discuss the function of autophagy in early mammalian embryogenesis.
Germline cells are the sole source of the transmission of genetic and epigenetic information to the next generation. Epigenetic information is reprogrammed during germ cell development to reacquire cellular totipotency and prevent the accumulation of epimutations. In this review, we summarize epigenetic reprogramming, in particular, DNA demethylation in developing primordial germ cells (PGCs). The recent development of next-generation sequencing, and the discovery of 5-methylcytosine oxidation are major breakthroughs in the study of epigenetic reprogramming in PGCs. DNA methylation analysis with high-throughput sequencing has uncovered the dynamics of DNA methylation erasure at single-locus resolution, which has revealed the global loss of DNA methylation in migrating PGCs, and locus-specific DNA demethylation in gonadal PGCs. The disruption of ten-eleven translocation genes shows that they are required for DNA demethylation at germline-specific genes in gonadal PGCs. These findings indicate that passive and active demethylation pathways operate synergistically and/or in parallel to ensure efficient global demethylation in developing PGCs.
Oocyte, embryo, ovarian tissue, and sperm cryopreservation before cancer treatments (aggressive chemotherapy/radiotherapy and bone marrow transplantation) are useful for the fertility preservation of cancer patients.This paper discusses the importance of the available treatment options including the risks, advantages and disadvantages of fertility preservation options. The reimplantation of contaminated ovarian tissue could be a life-threatening event. Therefore, the detection of minimal residual disease (MRD) is also discussed. Key words: Fertility preservation, Cryopreservation, Cancer, Pregnancy, Minimal residual disease (MRD) is also discussed.
The present study examined the effect of supplementation of the maturation medium with folic acid on the developmental competence of porcine oocytes as well as on the global DNA methylation of oocytes and histone acetylation in early developmental stage embryos. Supplementation of the maturation medium with 100 µM folic acid improved the development ratio of the oocytes to the blastocyst stage compared with those of oocytes that were cultured with either 0 or 10 µM folic acid. The global DNA methylation levels of the oocytes that matured with 100 µM folic acid were higher than those of oocytes that were cultured without folic acid, while the global DNA methylation levels of the oocytes decreased during maturation. Addition of either folic acid or 1.2 mM N-acetyl-cysteine (NAC) to the maturation medium significantly reduced the levels of reactive oxygen species in the oocytes. Supplementation of maturation medium with folic acid significantly enhanced the acetylation level of H4K8 and decreased the expression of histone deacetylase 1 (HADC1), whereas the addition of NAC did not affect the acetylation levels of H4K8 or HADC1. In addition, supplementation of maturation medium with 1.2 mM NAC did not improve the development rate to the blastocyst stage. In conclusion, folic acid added to the maturation medium affects not only the DNA methylation state of oocytes, but also the histone acetylation of early developmental stage embryos, as well as improving the developmental competence of the oocytes.