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Epigenetic Reprogramming in Early Embryo Development
Published in Cristina Camprubí, Joan Blanco, Epigenetics and Assisted Reproduction, 2018
As it is already known, the embryo is transcriptionally quiescent at the initial stages, and only the maternal proteins and RNAs in the zygote cytoplasm lead the development. Later on, during the maternal-to-zygotic transition, the control is taken by the activated nuclear genome of the zygote itself, and this is also a phenomenon displayed on sequential waves (28), occurring in the major ZGA wave in humans at the 4–8-cell stage (29) and at the 2-cell stage in the mouse (28), having been associated to DNA demethylation (25,27). Since ZGA has similar time frames in the monkey than in humans (30,31), could it then be a plausible idea that the remethylation waves, observed at the zygote stage in the mouse (26) and at the 8-cell stage in the monkey (21) were, in some way, also connected with the ZGA waves and could play a role in its regulation, for instance, modifying the chromatin structure or recruiting other transcriptional machinery.
Epigenetics from Oocytes to Embryos
Published in Carlos Simón, Carmen Rubio, Handbook of Genetic Diagnostic Technologies in Reproductive Medicine, 2022
Dagnė Daškevičiūtė, Marta Sanchez-Delgado, David Monk
Gene expression drastically changes during gametogenesis in mammals, halting completely before these cells are fully mature. In mice, expression resumes shortly after fertilization, in a process termed zygotic genome activation (ZGA) (note, here we are using the strictest definition of the zygotic, the one-cell stage preceding the first cleavage division), in which developmentally important genes are expressed from the late one-cell stage. Fertilization represents the first step in the creation of an embryo and requires the successive completion of multiple complex processes before the formation of a totipotent embryo during a period termed the maternal-to-zygotic transition (MZT). Syngamy, the fusion of the two terminally differentiated haploid gametes to form a zygote, is followed by epigenetic reprogramming, genome activation, and the depletion of maternal-derived transcripts to give rise to unspecialized cells of the cleavage-stage embryo. Totipotency of the blastomeres is gradually lost as cleavages progress allowing for initial specification and the development of the blastocyst, resulting in the formation of the inner cell mass (ICM), which will develop into the embryo proper, and the trophectoderm (TE), the forbearer of the extraembryonic tissues and placenta. Recent studies describing these mechanisms have benefited from advances and innovations in low-input and single-cell technologies revealing that, despite subtle differencing in timing (Table 9.1), these events are largely conserved between mammalian species. In this chapter we will describe the recent progress in understanding epigenetic regulation during mammalian pre-implantation development including global DNA demethylation, paternal protamine exchange, redistribution of histone modifications, and gradual formation of higher-order architecture, as well as the defining steps in regulating ZGA and embryonic genome activation (EGA). Furthermore, we discuss their implications for embryo selection during assisted reproductive cycles and whether faults in these coordinated processes could contribute to human embryo arrest observed during assisted reproductive cycles.
MOS mutation causes female infertility with large polar body oocytes
Published in Gynecological Endocrinology, 2022
Guangzhong Jiao, Huayu Lian, Jinhao Xing, Lili Chen, Zhaoli Du, Xiaoyan Liu
MOS variant may also cause maternal mRNA decay disorder inducing the meiotic defect. In vertebrates, fully grown oocytes are arrested at the diplotene stage of meiosis I, and contain a large amount of maternal mRNAs that are translationally dormant [32]. Upon meiotic maturation, many maternal mRNAs are translationally activated followed by degradation during maternal to zygotic transition (MZT) [33]. The abnormality of maternal mRNA degradation is associated with human early embryonic arrest and embryonic genome activation failure [34]. Cytoplasmic polyadenylation element binding protein 1 (CPEB1) is a key oocyte factor that regulates translation of maternal mRNA encoding B-cell translocation gene 4 (Btg4), a MZT licensing factor [35]. ERK triggers the phosphorylation and degradation of CPEB1 at an early stage of oocyte meiotic resumption [36, 37]. Furthermore, ERK1/2 increases maternal mRNA translation by phosphorylating the poly(A) polymerase at three sites [38]. As MOS is a maternal-effect gene that is transiently translated during oocyte maturation and has been reported to regulate the translation of some mRNAs [39]. We suspected that MOS/ERK signal cascade may participate in mRNA decay during human oocytes maturation.
Time to re-evaluate ART protocols in the light of advances in knowledge about methylation and epigenetics: an opinion paper
Published in Human Fertility, 2018
Yves Menezo, Brian Dale, Kay Elder
The preimplantation embryo represents a dry mass of 75–100 nanograms, and this remains constant from days 1 to 4.5, before the phase of blastocyst expansion. This 4-day period consists of two phases: the first is maternally driven, from fertilization to 4–8 cells, and the embryo develops under the control of proteins and mRNAs that were stored in the oocyte during its growth in the follicle. Very little transcription takes place during this period, apart from some paternal Y-linked genes (Ao, Erickson, Winston, & Handyside 1994). The second phase starts late on day 3 after the maternal to zygotic transition, and is driven by both paternal and maternal genes. The female gamete has a crucial capacity for repairing DNA damage, with significant expression of genes involved in methylation errors: mismatch excision repair, direct reversal of damage and nucleotide excision repair (NER) (Ménézo, Russo, Tosti, El Mouatassim, & Benkhalifa, 2007; Ménézo, Dale, & Cohen, 2010).
Mitochondrial DNA copy number in cumulus granulosa cells as a predictor for embryo morphokinetics and chromosome status
Published in Systems Biology in Reproductive Medicine, 2023
Pitra Rahmawati, Budi Wiweko, Arief Boediono
One of the limiting factors that affect the success rate of IVF is high-quality of oocytes. Oogenesis can produce a competent oocyte with the capability of resuming meiosis. During fertilization with a single spermatozoon, a competent oocyte aids the sperm head decondensation, produces two pronuclei (PN), develops into a cleavage-stage embryo through blastomere division, undergoes from maternal to zygotic transition or embryonic genome activation (EGA), develops into a blastocyst which subsequently hatches for implantation to produce a pregnancy (Armstrong 2001). Assessment of oocyte competence is therefore vital to improve embryo selection for transfer (May-Panloup et al. 2007). Oocyte development and maturation are regulated by a system of bidirectional signaling between the oocyte and the surrounding cumulus granulosa cells (CGCs) for the supply of amino acids, pyruvates, nucleotides and cholesterols via gap junctions and paracrine factors (Gilchrist et al. 2004; Laurenço et al. 2014). Moreover, CGCs mitochondria directly produce ATP as the main energy source which drives oogenesis (Dumesic et al. 2016). Recent studies reported CGCs mtDNA copy numbers as good predictors of embryo quality in IVF, with a positive and negative predictive value of 84.4% and 82.1%, respectively (Ogino et al. 2016). In addition, embryo viability (Desquiret-Dumas et al. 2017), and embryo implantation potential (Taugourdeau et al. 2019) have also been associated with the CGCs mtDNA copy number. Nonetheless, further investigation is required. This study aims to evaluate the relationship between mtDNA copy number in CGCs, embryo morphokinetic parameters and chromosomal status.