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CATCH-seq analysis of 2PN, P1PN, Parthenogenetic, and Androgenetic zygotes.

ABSTRACT: Embryogenesis begins with a zygote, a single cell with two pronuclei that separately enclose maternal and paternal chromosomes. The functional significance of the separation of parental chromosomes into distinct pronuclei remains unexplored, despite the fact that one-pronuclear biparental zygotes are used clinically. Here, using a combination of mouse zygote manipulation, quantitative imaging and theoretical approaches, we show a cytoplasm-mediated competition mechanism between separate parental pronuclei that ensures developmental potential. This mechanism limits pronuclear volume and prevents epigenetic mark dysregulation, including loss of maternal trimethylated histones. One-pronuclear biparental zygotes lack this mechanism, resulting in a reduced rate of development to term. This low developmental potential can be rescued by competition-based or drug-based restoration of epigenetic marks. This study provides a spatial mechanism linking fertilization to the establishment of the full developmental potential for the next generation, highlighting caveats in clinical use of one-pronuclear biparental zygotes.

ORGANISM(S): Mus musculus

PROVIDER: GSE309547 | GEO | 2026/02/26

REPOSITORIES: GEO

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Cytoplasmic competition between separate parental pronuclei in zygotes

Project description:Embryogenesis begins with a zygote, a single cell with two pronuclei that separately enclose maternal and paternal chromosomes. The functional significance of the separation of parental chromosomes into distinct pronuclei remains unexplored, despite the fact that one-pronuclear biparental zygotes are used clinically. Here, using a combination of mouse zygote manipulation, quantitative imaging and theoretical approaches, we show a cytoplasm-mediated competition mechanism between separate parental pronuclei. This mechanism limits pronuclear volume and prevents the loss of epigenetic marks, including maternally inherited trimethylated histones. One-pronuclear biparental zygotes lack this mechanism, resulting in a reduced rate of development to term. This low developmental potential can be rescued by competition-based or drug-based restoration of epigenetic marks. In human zygotes, epigenetic loss correlates with pronuclear volume. This study provides insight into strategies to improve the clinical use of one-pronuclear biparental zygotes.

2026-02-26 | GSE231732 | GEO

CATCH-seq analysis of 1PN and 2PN zygotes.

Project description:Embryogenesis begins with a zygote, a single cell with two pronuclei that separately enclose maternal and paternal chromosomes. The functional significance of the separation of parental chromosomes into distinct pronuclei remains unexplored, despite the fact that one-pronuclear biparental zygotes are used clinically. Here, using a combination of mouse zygote manipulation, quantitative imaging and theoretical approaches, we show a cytoplasm-mediated competition mechanism between separate parental pronuclei that ensures developmental potential. This mechanism limits pronuclear volume and prevents epigenetic mark dysregulation, including loss of maternal trimethylated histones. One-pronuclear biparental zygotes lack this mechanism, resulting in a reduced rate of development to term. This low developmental potential can be rescued by competition-based or drug-based restoration of epigenetic marks. This study provides a spatial mechanism linking fertilization to the establishment of the full developmental potential for the next generation, highlighting caveats in clinical use of one-pronuclear biparental zygotes.

2026-02-26 | GSE279785 | GEO

Asymmetric Reprogramming Capacity of Parental Pronuclei in Mouse Zygote

Project description:It has been demonstrated previously that the reprogramming factors are sequestered in the pronuclei of zygote after fertilization, as the enucleated zygotes at interphase cannot support the development of cloned embryos whereas the enucleated zygotes at M-phase can reprogram somatic cells to full pluripotency. However, it remains unknown whether the parental pronucleus, derived either from the sperm or oocyte, possesses the similar reprogramming ability. Here, we provide evidence demonstrating that the parental pronuclei are asymmetric in reprogramming and the reprogramming factors reside mainly in the male pronucleus. As a result, only the female pronucleus-depleted mouse zygotes enucleated at M-phase of mitosis can support the somatic cell reprogramming, the derivation of chromosome transfer embryonic stem (ctES) cells with full pluripotency and the full term development of cloned embryos. In striking contrast, the male pronucleus-depleted zygotes enucleated at M-phase of mitosis fail to support the pre-implantation development of somatic cell cloned embryos. Furthermore, we demonstrated that the distinct epigenetic reprogramming ability of the parental pronucleus might contribute directly to the developmental difference of somatic cloned embryos. Our study highlights the developmental asymmetry of parental pronuclei in reprogramming.

2014-12-30 | GSE49148 | GEO

Cytoplasmic competition between separate parental pronuclei in zygotes

Project description:Cytoplasmic competition between separate parental pronuclei in zygotes

| PRJNA967384 | ENA

Cytoplasmic competition between separate parental pronuclei in zygotes.

Project description:Cytoplasmic competition between separate parental pronuclei in zygotes.

| PRJNA1174679 | ENA

Active and Passive Demethylation of Male and Female Pronuclear DNA in the Mammalian Zygote

Project description:The epigenomes of mammalian sperm and oocytes, characterized by gamete-specific 5-methylcytosine (5mC) patterns, are reprogrammed during early embryogenesis to establish full developmental potential. Previous studies have suggested that the paternal genome is actively demethylated in the zygote while the maternal genome undergoes subsequent passive demethylation via DNA replication during cleavage. Active demethylation is known to depend on 5mC oxidation by Tet dioxygenases and excision of oxidized bases by thymine DNA glycosylase (TDG). Here we show that both maternal and paternal genomes undergo widespread active and passive demethylation in zygotes before the first mitotic division. Passive demethylation was blocked by the replication inhibitor aphidicolin, and active demethylation was abrogated by deletion of Tet3 in both pronuclei. At actively demethylated loci, 5mCs were processed to unmodified cytosines. Surprisingly, the demethylation process was unaffected by the deletion of TDG from the zygote, suggesting the existence of other demethylation mechanisms downstream of Tet3-mediated oxidation. The dataset includes RRBS anlysis of 2 MII oocyte samples, 3 WT female pronuclei samples PN3-4 stage, 2 Tet3 KO female pronuclei samples and 2 Aphidicolin treated female pronuclei samples. Also as male counterpart, a Sperm sample, 2 WT male pronuclei samples PN3-4 stage, 2 Tet3 KO male pronuclei samples and 2 Aphidicolin treated male pronuclei samples were included.

2014-09-11 | E-GEOD-56650 | biostudies-arrayexpress

Mus musculus

Project description:Asymmetric Reprogramming Capacity of Parental Pronuclei in Mouse Zygote

| PRJNA213147 | ENA

Multipolar zygotic divisions are characterized by parental genome segregation errors

Project description:The first mitotic division causes both parental genomes present in the zygote to segregate into two biparental diploid daughter cells. This fundamental tenet was challenged by the observation that blastomeres with different genome ploidy and distinct parental genotypes can coexist within individual embryos. We hypothesized that whole parental genomes can segregate into distinct blastomere lines during the multipolar division of the zygote, a phenomenon referred to as “heterogoneic” cell division. Here, we provide evidence of genome-wide segregation errors in two human blastocysts and further pinpoint its origin in a bovine model by mapping the genomic landscape of 82 blastomeres from 25 embryos that underwent multipolar division at the zygote stage using genome-wide SNP arrays and sequencing. In most embryos, the coexistence of androgenetic and diploid or polyploid blastomeres with or without anuclear blastomeres, androgenetic and anuclear blastomeres, and androgenetic and gynogenetic blastomeres within the same embryo provided proof that multipolar zygotic division coincides with heterogoneic segregation of the parental genome. By mapping the segregational origin of the genomic content, we deduced distinct segregation mechanisms underlying heterogoneic cell division including segregation by a tripolar spindle, the pronuclear extrusion of a paternal genome and, the operation of an ectopic paternal or private parental spindles. Polyspermic embryos expel excessive paternal genomes resulting in an androgenetic or polyploid blastomere. Confirming the results in human blastocysts we found genome-wide segregation errors to persist in bovine blastocysts.

2021-08-21 | GSE182345 | GEO

Active Demethylation of Both Maternal and Paternal Genomes in Mouse Zygotes

Project description:The epigenomes of mammalian sperm and oocytes, characterized by gamete-specific 5-methylcytosine (5mC) patterns, are reprogrammed in early embryogenesis to establish full developmental potential. It is broadly accepted that the paternal genome is actively demethylated in the zygote while the maternal genome undergoes passive demethylation thanks to DNA replication over the subsequent cleavage divisions. Here we reveal that both maternal and paternal genomes undergo widespread active and passive demethylation in the pronuclear zygote before the first mitotic division. Whereas the passive demethylation requires DNA replication, the active demethylation relies on enzymatic oxidation of 5mC, as deletion of the DNA dioxygenase, Tet3, but not the inhibition of replication, blocks the active demethylation. At actively demethylated loci, 5mCs appear to be processed to unmodified cytosines in a manner independent of the DNA glycosylase TDG. These observations suggest the occurrence of genuine active demethylation in both parental genomes following fertilization. An extra supportive Tet3 knock-out female pronuclear sample related to experiment Series GSE56650.

2016-09-01 | E-GEOD-60777 | biostudies-arrayexpress

Maternal to zygotic transition：A two-step process with two phases of ZGA occurs in zygote right after fertilization in Arabidopsis

Project description:The goal of the present study is to analyze the characteristics of maternal to zygotic transition (MZT) in Arabidopsis. The maternal-to-zygotic transition (MZT) is an essential developmental turning point during the alternation of generations in both plants and animals. In animals, early embryogenesis is maternally controlled and zygotic genome activation (ZGA) starts much later. However, in plants, the timing of MZT and parental contributions to the zygotic transcriptome remain unclear. To address above mentioned questions, we selected Arabidopsis as model plant for the analysis. Regarding to the characteristics of MZT, egg cells, embryos including spherical zygote, elongated zygote, 1-cell embryo and 32-cell embryo were isolated and collected for RNA sequencing. Hybrid zygotes at two representative stages from the reciprocal crosses between polymorphic Arabidopsis Columbia (Col) and Landsberg erecta (Ler) accessions were also sequenced for investigating the parental contributions. We demonstrate that plant MZT occurs during the zygote stage and is a two-step process, first involving rapid maternal transcript degradation and, second, large-scale de novo transcription. Parental contributions to the zygotic transcriptome are stage dependent over the course of zygote development; the spherical zygote is characterized by a maternally dominated transcriptome, whereas the elongated zygote genome shows equal parental contributions.

2019-05-12 | GSE121003 | GEO

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