Paternally inherited H3K27me3 affects chromatin accessibility in mouse embryos produced by round spermatid injection
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ABSTRACT:
PROVIDER: PRJNA807595 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18050782_1.fastq.gz | Fastqsanger.gz | |||
| SRR18050782_2.fastq.gz | Fastqsanger.gz | |||
| SRR18050783_1.fastq.gz | Fastqsanger.gz | |||
| SRR18050783_2.fastq.gz | Fastqsanger.gz | |||
| SRR18050784_1.fastq.gz | Fastqsanger.gz |
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Project description:Round spermatid injection (ROSI) results in a lower birth rate than intracytoplasmic sperm injection, which has hampered its clinical application. Inefficient development of ROSI embryos has been attributed to epigenetic abnormalities. However, the chromatin-based mechanism that underpins the low birth rate in ROSI remains to be determined. Here, we show that a repressive histone mark H3K27me3 persists from mouse round spermatids into zygotes in ROSI and that round spermatid-derived H3K27me3 is associated with less accessible chromatin and impaired gene expression in ROSI embryos. These loci are initially marked by H3K27me3 but undergo histone modification remodelling in spermiogenesis, resulting in reduced H3K27me3 in normal spermatozoa. Therefore, the absence of the epigenetic remodelling, presumably mediated by histone turnover during spermiogenesis, leads to dysregulation of chromatin accessibility and transcription in ROSI embryos. Thus, our results unveil a molecular logic, in which chromatin states in round spermatids impinge on chromatin accessibility and transcription in ROSI embryos, highlighting the importance of epigenetic remodelling during spermiogenesis in successful reproduction.
2022-08-22 | GSE196859 | GEO
Project description:Paternally inherited H3K27me3 impacts zygotic genome activation in round spermatid injection [RNA-seq]
| PRJNA807596 | ENA
Project description:Paternally inherited H3K27me3 impacts zygotic genome activation in round spermatid injection [ATAC-seq]
| PRJNA807599 | ENA
Project description:Round spermatid injection (ROSI) gives rise to a lower birth rate than intracytoplasmic sperm injection (ICSI), which uses mature spermatozoa and has limited clinical application. Inefficient development of ROSI-embryos has been attributed to epigenetic abnormalities. However, the chromatin-based mechanism that underpins the low birth rate of ROSI remains to be determined. Here we show that a repressive histone mark H3K27me3 persists from doner round spermatids into zygotes in ROSI and that paternally derived H3K27me3 is associated with less accessible chromatin and impaired zygotic genome activation (ZGA) in ROSI-derived zygotes. These H3K27me3 marked loci in the paternal germline undergo histone turnover in spermiogenesis, resulting in the reduced paternal H3K27me3 in normal spermatozoa. Thus, the lack of histone turnover during spermiogenesis led to the dysregulation of chromatin accessibility and ZGA in ROSI-embryos. Our results unveil a molecular logic by which chromatin states in round spermatids impinge on chromatin states and ZGA in ROSI-embryos, highlighting the importance of chromatin remodeling in spermiogenesis in successful reproduction.
2022-08-23 | GSE196858 | GEO
Project description:Round spermatid injection (ROSI) gives rise to a lower birth rate than intracytoplasmic sperm injection (ICSI), which uses mature spermatozoa and has limited clinical application. Inefficient development of ROSI-embryos has been attributed to epigenetic abnormalities. However, the chromatin-based mechanism that underpins the low birth rate of ROSI remains to be determined. Here we show that a repressive histone mark H3K27me3 persists from doner round spermatids into zygotes in ROSI and that paternally derived H3K27me3 is associated with less accessible chromatin and impaired zygotic genome activation (ZGA) in ROSI-derived zygotes. These H3K27me3 marked loci in the paternal germline undergo histone turnover in spermiogenesis, resulting in the reduced paternal H3K27me3 in normal spermatozoa. Thus, the lack of histone turnover during spermiogenesis led to the dysregulation of chromatin accessibility and ZGA in ROSI-embryos. Our results unveil a molecular logic by which chromatin states in round spermatids impinge on chromatin states and ZGA in ROSI-embryos, highlighting the importance of chromatin remodeling in spermiogenesis in successful reproduction.
2022-08-23 | GSE196857 | GEO
Project description:In mouse female preimplantation embryos, the paternal X chromosome (Xp) is silenced by imprinted X chromosome inactivation (iXCI). This requires production of the noncoding Xist RNA in cis, from the Xp. The Xist locus on the maternally inherited X chromosome (Xm) is refractory to activation due to the presence of an imprint. Paternal inheritance of an Xist deletion (XpΔXist) is embryonic lethal to female embryos, due to iXCI abolishment. Here, we circumvented the histone-to-protamine and protamine-to-histone transitions of the paternal genome, by fertilization of oocytes via injection of round spermatids (ROSI). This did not affect initiation of XCI in wild type female embryos. Surprisingly, ROSI using ΔXist round spermatids allowed survival of female embryos. This was accompanied by activation of the intact maternal Xist gene, initiated with delayed kinetics, around the morula stage, resulting in Xm silencing. Maternal Xist gene activation was not observed in ROSI-derived males. In addition, no Xist expression was detected in male and female morulas that developed from oocytes fertilized with mature ΔXist sperm. Finally, the expression of the X-encoded XCI-activator RNF12 was enhanced in both male (wild type) and female (wild type as well as XpΔXist) ROSI derived embryos, compared to in vivo fertilized embryos. Thus, high RNF12 levels may contribute to the specific activation of maternal Xist in XpΔXist female ROSI embryos, but upregulation of additional Xp derived factors and/or the specific epigenetic constitution of the round spermatid-derived Xp are expected to be more critical. These results illustrate the profound impact of a dysregulated paternal epigenome on embryo development, and we propose that mouse ROSI can be used as a model to study the effects of intergenerational inheritance of epigenetic marks.
| S-EPMC5065126 | biostudies-literature
Project description:Generation of haploid gametes in vitro can potentially address gamete failure-based infertility.This study reports complete in vitro meiosis from murine ESC-derived PGCLCs resulting in the formation of male spermatid-like cells (SLCs) capable of producing viable fertile offspring via intracytoplasmic sperm injection (ICSI).Our findings provide the basis for generation of haploid spermatids in vitro in human, the generation of transgenic animals, and the use of this system to investigate mechanisms of meiosis. We used microarrays to compare gene expression profiles of in vivo and in vitro derived PGC cells and round spermatids. We collected E12.5 male fatal PGCs, PGCLC in vitro, round spermatids and spermatids like cells produced in vitro, each sample has 3 replications.
2016-02-26 | E-GEOD-71478 | biostudies-arrayexpress
Project description:During the human in vitro fertilization procedure in the assisted reproductive technology, intracytoplasmic sperm injection is routinely used to inject a spermatozoon or a less mature elongating spermatid into the oocyte. In some infertile men, round spermatids (haploid male germ cells that have completed meiosis) are the most mature cells visible during testicular biopsy. The microsurgical injection of a round spermatid into an oocyte as a substitute is commonly referred to as round spermatid injection (ROSI). Currently, human ROSI is considered a very inefficient procedure and of no clinical value. Herein, we report the birth and development of 14 children born to 12 women following ROSI of 734 oocytes previously activated by an electric current. The round spermatids came from men who had been diagnosed as not having spermatozoa or elongated spermatids by andrologists at other hospitals after a first Micro-TESE. A key to our success was our ability to identify round spermatids accurately before oocyte injection. As of today, all children born after ROSI in our clinic are without any unusual physical, mental, or epigenetic problems. Thus, for men whose germ cells are unable to develop beyond the round spermatid stage, ROSI can, as a last resort, enable them to have their own genetic offspring.
| S-EPMC4664346 | biostudies-other
Project description:The E3 ubiquitin ligase Ube3a is biallelically expressed in mitotic cells, including neural progenitors and glial cells, raising the possibility that UBE3A gain-of-function mutations might cause neurodevelopmental disorders irrespective of parent-of-origin. To test this possibility, we engineered a mouse line that harbors an autism-linked UBE3A-T485A (T508A in mouse) gain-of-function mutation and evaluated phenotypes in animals that inherited the mutant allele paternally, maternally, or from both parents. We found that both paternally and maternally expressed UBE3A-T485A resulted in elevated UBE3A activity in neural progenitors and glial cells where Ube3a is biallelically expressed. Expression of UBE3A-T485A from the maternal allele, but not the paternal one, led to a persistent elevation of UBE3A activity in postmitotic neurons. Maternal, paternal, or biparental inheritance of the mutant allele promoted embryonic expansion of Zcchc12 lineage interneurons which mature into Sst and Calb2 expressing interneurons, and caused a spectrum of behavioral phenotypes that differed by parent-of-origin. Phenotypes were distinct from those observed in Angelman syndrome model mice that harbor a Ube3a maternal loss-of-function allele. Our study shows that the UBE3A-T485A gain-of-function mutation causes distinct neurodevelopmental phenotypes when inherited maternally or paternally. These findings have clinical implications for a growing number of disease-linked UBE3A gain-of-function mutations.
2023-07-03 | GSE201733 | GEO
Project description:The E3 ubiquitin ligase Ube3a is biallelically expressed in mitotic cells, including neural progenitors and glial cells, raising the possibility that UBE3A gain-of-function mutations might cause neurodevelopmental disorders irrespective of parent-of-origin. To test this possibility, we engineered a mouse line that harbors an autism-linked UBE3A-T485A (T508A in mouse) gain-of-function mutation and evaluated phenotypes in animals that inherited the mutant allele paternally, maternally, or from both parents. We found that both paternally and maternally expressed UBE3A-T485A resulted in elevated UBE3A activity in neural progenitors and glial cells where Ube3a is biallelically expressed. Expression of UBE3A-T485A from the maternal allele, but not the paternal one, led to a persistent elevation of UBE3A activity in postmitotic neurons. Maternal, paternal, or biparental inheritance of the mutant allele promoted embryonic expansion of Zcchc12 lineage interneurons which mature into Sst and Calb2 expressing interneurons, and caused a spectrum of behavioral phenotypes that differed by parent-of-origin. Phenotypes were distinct from those observed in Angelman syndrome model mice that harbor a Ube3a maternal loss-of-function allele. Our study shows that the UBE3A-T485A gain-of-function mutation causes distinct neurodevelopmental phenotypes when inherited maternally or paternally. These findings have clinical implications for a growing number of disease-linked UBE3A gain-of-function mutations.
2023-07-03 | GSE201731 | GEO