Deletion of maternal UHRF1 severely reduces mouse oocyte quality and causes developmental defects in preimplantation embryos

Cao, Yumeng; Li, Mingrui; Liu, Fei; Ni, Xiaobei; Wang, Shuai; Zhang, Hao; Sui, Xuesong; Huo, Ran

doi:10.1096/fj.201801696rrrr

Cited by 18 publications

(21 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present study, scRNA-seq demonstrated that for in vitro and in vivo embryos, expression of chromatin factors and transcriptional factors had large differences, suggesting that the in vitro embryo culture system could significantly alter the gene expression and influence the developmental ability. For DNA methylation factors (UHRF1/2 and DNMT1/3A/3B), expression levels and changing trends were very different between in vitro and in vivo embryos, indicating that DNA methylation difference caused by these factors might possibly affect the transcription integrity 51 and preimplantation development 52 . Similar results for factors related to H3K4 methylation and transcription were also found to be different between in vitro and in vivo groups.…”

Section: Discussionmentioning

confidence: 99%

Single cell RNA-seq reveals genes vital to in vitro fertilized embryos and parthenotes in pigs

Liang

Liu

et al. 2021

Sci Rep

View full text Add to dashboard Cite

Successful early embryo development requires the correct reprogramming and configuration of gene networks by the timely and faithful execution of zygotic genome activation (ZGA). However, the regulatory principle of molecular elements and circuits fundamental to embryo development remains largely obscure. Here, we profiled the transcriptomes of single zygotes and blastomeres, obtained from in vitro fertilized (IVF) or parthenogenetically activated (PA) porcine early embryos (1- to 8-cell), focusing on the gene expression dynamics and regulatory networks associated with maternal-to-zygote transition (MZT) (mainly maternal RNA clearance and ZGA). We found that minor and major ZGAs occur at 1-cell and 4-cell stages for both IVF and PA embryos, respectively. Maternal RNAs gradually decay from 1- to 8-cell embryos. Top abundantly expressed genes (CDV3, PCNA, CDR1, YWHAE, DNMT1, IGF2BP3, ARMC1, BTG4, UHRF2 and gametocyte-specific factor 1-like) in both IVF and PA early embryos identified are of vital roles for embryo development. Differentially expressed genes within IVF groups are different from that within PA groups, indicating bi-parental and maternal-only embryos have specific sets of mRNAs distinctly decayed and activated. Pathways enriched from DEGs showed that RNA associated pathways (RNA binding, processing, transport and degradation) could be important. Moreover, mitochondrial RNAs are found to be actively transcribed, showing dynamic expression patterns, and for DNA/H3K4 methylation and transcription factors as well. Taken together, our findings provide an important resource to investigate further the epigenetic and genome regulation of MZT events in early embryos of pigs.

show abstract

Section: Discussionmentioning

confidence: 99%

Single cell RNA-seq reveals genes vital to in vitro fertilized embryos and parthenotes in pigs

Liang

Liu

et al. 2021

Sci Rep

View full text Add to dashboard Cite

show abstract

“…In addition, UHRF1 gene polymorphisms are closely associated with oligospermia in Chinese men 44 . Although the process of oogenesis was not affected, a large proportion of the embryos derived from the Uhrf1 ‐knockout (KO) oocytes died before reaching the blastocyst stage, which might have been caused by a maternal effect 45,46 . However, the underlying mechanisms remain unknown.…”

Section: Discussionmentioning

confidence: 99%

“…44 Although the process of oogenesis was not affected, a large proportion of the embryos derived from the Uhrf1knockout (KO) oocytes died before reaching the blastocyst stage, which might have been caused by a maternal effect. 45,46 However, the underlying mechanisms remain unknown. Our results showed that UHRF1 was localized in the cytoplasm of CTB, STB, and villi columns, and its expression was significantly decreased in the villi of patients with RPL.…”

Section: Myd88/nf-κb Signaling Pathway Promoted the Pro-inflammatory ...mentioning

confidence: 99%

UHRF1 shapes both the trophoblast invasion and decidual macrophage differentiation in early pregnancy

Liu

Wang

et al. 2022

The FASEB Journal

View full text Add to dashboard Cite

Trophoblasts play critical roles in establishment and maintenance of a normal pregnancy. Their dysfunction in early pregnancy is closely related to pregnancy‐related diseases, including recurrent pregnancy loss (RPL). Epigenetic modifications dynamically change during pregnancy; however, the role of the epigenetic modifier UHRF1 in trophoblast regulation remains unknown. This is the first study to show that UHRF1 expression was localized in the cytoplasm of cytotrophoblasts, syncytiotrophoblasts, and villi columns, and decreased in the villi of patients with RPL. The invasion and cell viability in a UHRF1 knockdown trophoblast cell line were significantly decreased. In addition, the mRNA expression profiles of Swan71 cells were partially altered by UHRF1 knockdown. The altered immune‐related genes were screened out and the pro‐inflammatory TH1‐type chemokine/cytokines CXCL2 and IL‐1β were identified as the most promising targets of UHRF1 in the trophoblasts, which were significantly increased in the UHRF1 knockdown Swan71 cells, villi, and serum from patients with RPL. The macrophages treated with the supernatants of UHRF1 knockdown Swan71 cells were polarized to the M1 phenotype and secreted high levels of pro‐inflammatory cytokines, which might be driven by the activated MyD88/NF‐κB signaling pathway and mediated by the increased expression of CXCR2 and IL‐1R1 (CXCL2 and IL‐1β receptors, respectively). In addition, the supernatants of UHRF1 knockdown Swan71 cells showed stronger chemotaxis to macrophages than those from the controls. Our findings highlight the previously unknown roles of UHRF1 as one of the key regulators on the trophoblasts and their cross‐talk with local immune cells, and demonstrate a potential approach for RPL intervention.

show abstract

“…Uhrf1 deficiency is reported to alter the epigenetic pattern of several target genes and consequently induce transcriptomic changes resulting in developmental abnormalities. Deletion of maternal Uhrf1 causes developmental defects in preimplantation embryos [34], while at pre-gastrulation stage, altered uhrf1 expression results in embryonic lethality [23]. Knockout of zebrafish uhrf1 and dnmt1 presented defects in lens formation and microphthalmia [24], while conditional Uhrf1 deficiency in mouse model increased the expression of several genes including Hspb1, a gene involved in chondrocyte differentiation [35] and suppressed osteoblast activity [36].…”

Section: Discussionmentioning

confidence: 99%

Hmx1 regulates urfh1 expression in the craniofacial region in zebrafish

2021

View full text Add to dashboard Cite

H6 family homeobox 1 (HMX1) regulates multiple aspects of craniofacial development as it is widely expressed in the eye, peripheral ganglia and branchial arches. Mutations in HMX1 are linked to an ocular defect termed Oculo-auricular syndrome of Schorderet-Munier-Franceschetti (MIM #612109). We identified UHRF1 as a target of HMX1 during development. UHRF1 and its partner proteins actively regulate chromatin modifications and cellular proliferation. Luciferase assays and in situ hybridization analyses showed that HMX1 exerts a transcriptional inhibitory effect on UHRF1 and a modification of its expression pattern. Overexpression of hmx1 in hsp70-hmx1 zebrafish increased uhrf1 expression in the cranial region, while mutations in the hmx1 dimerization domains reduced uhrf1 expression. Moreover, the expression level of uhrf1 and its partner dnmt1 was increased in the eye field in response to hmx1 overexpression. These results indicate that hmx1 regulates uhrf1 expression and, potentially through regulating the expression of factors involved in DNA methylation, contribute to the development of the craniofacial region of zebrafish.

show abstract

Deletion of maternal UHRF1 severely reduces mouse oocyte quality and causes developmental defects in preimplantation embryos

Cited by 18 publications

References 53 publications

Single cell RNA-seq reveals genes vital to in vitro fertilized embryos and parthenotes in pigs

Single cell RNA-seq reveals genes vital to in vitro fertilized embryos and parthenotes in pigs

UHRF1 shapes both the trophoblast invasion and decidual macrophage differentiation in early pregnancy

Hmx1 regulates urfh1 expression in the craniofacial region in zebrafish

Contact Info

Product

Resources

About