Chromatin Accessibility Landscape in Human Early Embryos and Its Association with Evolution.

The dynamics of the chromatin regulatory landscape during human early embryogenesis remains unknown. Using DNase I hypersensitive site (DHS) sequencing, we report that the chromatin accessibility landscape is gradually established during human early embryogenesis. Interestingly, the DHSs with OCT4 binding motifs are enriched at the timing of zygotic genome activation (ZGA) in humans, but not in mice. Consistently, OCT4 contributes to ZGA in humans, but not in mice. We further find that lower CpG promoters usually establish DHSs at later stages. Similarly, younger genes tend to establish promoter DHSs and are expressed at later embryonic stages, while older genes exhibit these features at earlier stages. Moreover, our data show that human active transposons SVA and HERV-K harbor DHSs and are highly expressed in early embryos, but not in differentiated tissues. In summary, our data provide an evolutionary developmental view for understanding the regulation of gene and transposon expression.

CHK1 controls zygote pronuclear envelope breakdown by regulating F-actin through interacting with MICAL3.

CHK1 mutations could cause human zygote arrest at the pronuclei stage, a phenomenon that is not well understood at the molecular level. In this study, we conducted experiments where pre-pronuclei from zygotes with CHK1 mutation were transferred into the cytoplasm of normal enucleated fertilized eggs. This approach rescued the zygote arrest caused by the mutation, resulting in the production of a high-quality blastocyst. This suggests that CHK1 dysfunction primarily disrupts crucial biological processes occurring in the cytoplasm. Further investigation reveals that CHK1 mutants have an impact on the F-actin meshwork, leading to disturbances in pronuclear envelope breakdown. Through co-immunoprecipitation and mass spectrometry analysis of around 6000 mouse zygotes, we identified an interaction between CHK1 and MICAL3, a key regulator of F-actin disassembly. The gain-of-function mutants of CHK1 enhance their interaction with MICAL3 and increase MICAL3 enzymatic activity, resulting in excessive depolymerization of F-actin. These findings shed light on the regulatory mechanism behind pronuclear envelope breakdown during the transition from meiosis to the first mitosis in mammals.

Key role for CTCF in establishing chromatin structure in human embryos.

In the interphase of the cell cycle, chromatin is arranged in a hierarchical structure within the nucleus1,2, which has an important role in regulating gene expression3-6. However, the dynamics of 3D chromatin structure during human embryogenesis remains unknown. Here we report that, unlike mouse sperm, human sperm cells do not express the chromatin regulator CTCF and their chromatin does not contain topologically associating domains (TADs). Following human fertilization, TAD structure is gradually established during embryonic development. In addition, A/B compartmentalization is lost in human embryos at the 2-cell stage and is re-established during embryogenesis. Notably, blocking zygotic genome activation (ZGA) can inhibit TAD establishment in human embryos but not in mouse or Drosophila. Of note, CTCF is expressed at very low levels before ZGA, and is then highly expressed at the ZGA stage when TADs are observed. TAD organization is significantly reduced in CTCF knockdown embryos, suggesting that TAD establishment during ZGA in human embryos requires CTCF expression. Our results indicate that CTCF has a key role in the establishment of 3D chromatin structure during human embryogenesis.

Splicing factor ESRP1 derived circ_0068162 promotes the progression of oral squamous cell carcinoma via the miR-186/JAG axis.

OBJECTIVES: Oral squamous cell carcinoma (OSCC) is a common malignancy in the oral and maxillofacial regions with an increasing incidence rate. Circular RNA (circRNA) is a recently discovered long-chain non-coding RNA family member. The objective of this study was to analyze the role of circ_0068162 in OSCC development. METHODS: We downloaded sample data GSE145608 from the Gene Expression Omnibus database. Online databases Starbase, TargetScan and miRDB were used to predict the target microRNAs (miRNAs) and genes. Cell viability and proliferation were assessed using the CCK-8 and EdU assays, respectively. Cell migration and invasion abilities were detected using transwell assay. The double luciferase reporter and RNA immunoprecipitation (RIP) assays were performed to verify the interaction relationship between the identified target molecules. RNase R and actinomycin D treatment were performed to analyze the stability of circ_0068162. RESULTS: We found that circ_0068162 was overexpressed in the cytoplasm of OSCC cells and clinical OSCC tissues. Knockdown of circ_0068162 inhibited the growth, migration and invasion of OSCC cells. We also identified miR-186 as the target miRNA of circ_0068162, and JAG1 and JAG2 as the target genes of miR-186. The miR-186 inhibitor rescued the effects of sh-circ_0068162 and JAG1/JAG2 overexpression rescued the effects of miR-186 mimic in OSCC cells. Furthermore, ESRP1 promoted the biosynthesis of circ_0068162. CONCLUSIONS: The circ_0068162/miR-186/JAGs/ESRP1 feedback loop is closely related to OSCC development.

Influences of ultrasound osteotome on wound infection and wound complications following removal of mandibular wisdom teeth.

We conducted this study to assess the effect of ultrasound osteotome on surgical site wound infection and pain following removal of mandibular wisdom teeth. A computerised search of Embase, Cochrane Library, PubMed, Wanfang and China National Knowledge Infrastructure databases for publicly available randomised controlled trials (RCTs) on the clinical effects of applying ultrasound osteotome to extract mandibular wisdom teeth was conducted from the inception of the databases to September 2023. Two researchers independently screened the retrieved results for literature screening, quality assessment and data extraction. RevMan 5.4 software was applied for data analysis. A total of 17 RCTs were included in this study, including 848 cases in the ultrasound osteotome group and 842 cases in the control group. The analysis revealed, compared with the control group, the ultrasound osteotome group showed a significantly lower incidence of postoperative wound infection (1.42% vs. 5.46%, odds ratio [OR]: 0.30, 95% confidence intervals [CI]: 0.17-0.53, p < 0.0001), fewer postoperative complications (6.35% vs. 22.12%, OR: 0.23, 95% CI: 0.17-0.32, p < 0.00001), shorter operative time (standardised mean differences [SMD]: -1.30, 95% CI: -1.97 to -0.64, p = 0.0001) and lower wound pain scores (SMD: -2.26 95% CI -2.80 to -1.73, p < 0.00001). Strong evidence suggests that ultrasound osteotome applied to extract mandibular wisdom teeth is more advantageous in terms of lower postoperative wound infection, less wound pain, fewer postoperative complications and shorter operative time compared with conventional treatment methods, but large-scale, multicentre RCTs are still needed to obtain more accurate results.

Post-ovulatory aging affects mitochondria, spindle and protein metabolism in mouse oocytes.

In brief: Post-ovulatory aging (POA) results in a decline in oocyte quality and embryonic developmental capacity although the underlying mechanisms remain elusive. This study provides comprehensive mRNA expression profiles of fresh and aging oocytes in mice for the first time. Abstract: POA impairs the quality of mammalian oocytes with harmful effects on the developmental potential of the embryo. This is a major problem for humans since it is associated with low rate of natural fertility, with high rate of spontaneous abortion and low efficiency of in vitro fertilization. However, the molecular mechanisms underlying this process remain unclear and new methods are demanded to control POA. In this study, we performed single-cell RNA-sequencing (scRNA-seq) analysis on fresh and aging MII mouse oocytes and compared their global RNA transcription patterns. Nine hundred and twenty-one differentially expressed genes (DEGs) were identified. Five hundred and sixty-nine genes were downregulated, while 356 were upregulated in the group of aging oocytes. Gene ontology (GO) enrichment analysis demonstrated that a series of DEGs were significantly enriched involving mitochondrial functions, spindle functions and protein metabolism. The results of qPCR and a series of functional tests further confirmed that the disorder of mitochondrial functions, spindle functions and impairment of protein metabolism were actually involved in the progression of POA. In this study, panoramic mRNA expression profiles of fresh and aging oocytes were depicted and fully validated. Our data will provide a useful resource for further research on the regulation of gene expression of POA and suggest potential strategies to delay and reverse POA.

Developmental toxicity of 2-bromoacetamide on peri- and early post-implantation mouse embryos in vitro.

2-bromoacetamide (BAcAm), a new class of disinfection by-products (DBPs), is widely detected in drinking water across the world. Reports of the high cytogenetic toxicity of BAcAm have aroused public attention concerning its toxic effects on early embryonic development. In this study, we optimized an in vitro culture (IVC) system for peri- and early post-implantation mouse embryos and used this system to determine the developmental toxicity of BAcAm. We found that exposure to BAcAm caused a reduction in egg cylinder formation rate and abnormal lineage differentiation in a dose-dependent manner. Transcriptomic analysis further revealed that BAcAm exposure at early developmental stages altered the abundance of transcripts related to a variety of biological processes including gene expression, metabolism, cell proliferation, cell death and embryonic development, thus indicating its toxic effects on embryonic development. Thus, we developed a robust tool for studying the toxicology of chemicals at the early stages of embryonic development and demonstrated the developmental toxicity of BAcAm in the early embryonic development of mammals.

A homozygous variant in TBPL2 was identified in women with oocyte maturation defects and infertility.

STUDY QUESTION: What are the genetic causes of oocyte maturation defects? SUMMARY ANSWER: A homozygous splicing variant (c.788 + 3A>G) in TATA-box binding protein like 2 (TBPL2) was identified as a contributory genetic factor in oocyte maturation defects. WHAT IS KNOWN ALREADY: TBPL2, a vertebrate oocyte-specific general transcription factor, is essential for oocyte development. TBPL2 variants have not been studied in human oocyte maturation defects. STUDY DESIGN, SIZE, DURATION: Two infertile families characterized by oocyte maturation defects were recruited for whole-exome sequencing (WES). PARTICIPANTS/MATERIALS, SETTING, METHODS: Genomic DNA was extracted from peripheral blood for WES analysis. Sanger sequencing was performed for data validation. Pathogenicity of variants was predicted by in silico analysis. Minigene assay and single-oocyte RNA sequencing were performed to investigate the effects of the variant on mRNA integrity and oocyte transcriptome, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: A homozygous splicing variant (c.788 + 3A>G) in TBPL2 was identified in two unrelated families characterized by oocyte maturation defects. Haplotype analysis indicated that the disease allele of Families 1 and 2 was independent. The variant disrupted the integrity of TBPL2 mRNA. Transcriptome sequencing of affected oocytes showed that vital genes for oocyte maturation and fertilization were widely and markedly downregulated, suggesting that a mutation in the transcriptional factor, TBPL2, led to global gene alterations in oocytes. LIMITATIONS, REASONS FOR CAUTION: Limitations include the lack of direct functional evidence. Owing to the scarcity of human oocyte samples, only two immature MI oocytes were obtained from the patients, and we could only investigate the effect of the mutation at the transcriptional level by high-throughput sequencing technology. No extra oocytes were obtained to assess the transcriptional activity of the mutant oocytes by immunofluorescence, or investigate the effects on the binding of TBPL2 caused by the mutation. WIDER IMPLICATIONS OF THE FINDINGS: Our findings highlight a critical role of TBPL2 in female reproduction and identify a homozygous splicing mutation in TBPL2 that might be related to defects in human oocyte maturation. This information will facilitate the genetic diagnosis of infertile individuals with repeated failures of IVF, providing a basis for genetic counseling. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Key Research and Development Program of China (2018YFC1004000, 2017YFC1001504 and 2017YFC1001600), the National Natural Science Foundation of China (81871168, 31900409 and 31871509), the Foundation for Distinguished Young Scholars of Shandong Province (JQ201816), the Innovative Research Team of High-Level Local Universities in Shanghai (SSMU-ZLCX20180401) and the Fundamental Research Funds of Shandong University. The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Maternal Sall4 Is Indispensable for Epigenetic Maturation of Mouse Oocytes.

Sall4 (Splat-like 4) plays important roles in maintaining pluripotency of embryonic stem cells and in various developmental processes. Here, we find that Sall4 is highly expressed in oocytes and early embryos. To investigate the roles of SALL4 in oogenesis, we generated Sall4 maternal specific knock-out mice by using CRISPR/Cas9 system, and we find that the maternal deletion of Sall4 causes developmental arrest of oocytes at germinal vesicle stage with non-surrounded nucleus, and the subsequent meiosis resumption is prohibited. We further discover that the loss of maternal Sall4 causes failure in establishment of DNA methylation in oocytes. Furthermore, we find that Sall4 modulates H3K4me3 and H3K27me3 modifications by regulating the expression of key histone demethylases coding genes Kdm5b, Kdm6a, and Kdm6b in oocytes. Moreover, we demonstrate that the aberrant H3K4me3 and H3K27me3 cause mis-expression of genes that are critical for oocytes maturation and meiosis resumption. Taken together, our study explores a pivotal role of Sall4 in regulating epigenetic maturation of mouse oocytes.

[Study on the value of systemic immune inflammation index and nomogram in predicting the prognosis of patients with mucoepidermoid carcinoma].

PURPOSE: To investigate the relationship between preoperative systemic immune-inflammation index (SII) and relapse-free survival (RFS) after surgical resection of mucoepidermoid carcinoma(MEC). METHODS: The data of 135 patients with MEC who underwent surgical resection in the First Affiliated Hospital of Zhengzhou University from January 2016 to July 2019 were collected, and the receiver operating characteristic(ROC) curve was performed on the SII of patients. The optimal cut-off value was obtained by ROC analysis. Therefore, the patients' SII index was divided into high and low group, and survival analysis was performed by Kaplan-Meier method. Cox proportional regression model and least absolute shrinkage and selection operator (LASSO) were used to analyze the factors influencing prognosis, and a nomogram model was built to predict patients' relapse-free survival(RFS). Area under curve (AUC) and correction curve were used to evaluate the model and verify the consistency. RESULTS: Survival analysis showed that the RFS rate in low SII group was significantly higher than that in high SII group. Cox proportional hazard regression model showed high SII(HR=2.179, 95%CI: 1.072-4.426, P=0.031) and low tumor differentiation(HR=6.894, 95%CI: 2.770-17.158, P=0.000) and cervical lymph node metastasis (HR=2.091, 95%CI: 1.034-4.230, P=0.040) were significant predictors of poor RFS. CONCLUSIONS: The lower the preoperative SII, the better the prognosis of patients. The nomogram prognosis of MEC based on SII is effective.

Maternal mRNA deadenylation is defective in in vitro matured mouse and human oocytes.

Oocyte in vitro maturation is a technique in assisted reproductive technology. Thousands of genes show abnormally high expression in in vitro maturated metaphase II (MII) oocytes compared to those matured in vivo in bovines, mice, and humans. The mechanisms underlying this phenomenon are poorly understood. Here, we use poly(A) inclusive RNA isoform sequencing (PAIso-seq) for profiling the transcriptome-wide poly(A) tails in both in vivo and in vitro matured mouse and human oocytes. Our results demonstrate that the observed increase in maternal mRNA abundance is caused by impaired deadenylation in in vitro MII oocytes. Moreover, the cytoplasmic polyadenylation of dormant Btg4 and Cnot7 mRNAs, which encode key components of deadenylation machinery, is impaired in in vitro MII oocytes, contributing to reduced translation of these deadenylase machinery components and subsequently impaired global maternal mRNA deadenylation. Our findings highlight impaired maternal mRNA deadenylation as a distinct molecular defect in in vitro MII oocytes.

Allelic reprogramming of chromatin states in human early embryos.

The reprogramming of parental epigenomes in human early embryos remains elusive. To what extent the characteristics of parental epigenomes are conserved between humans and mice is currently unknown. Here, we mapped parental haploid epigenomes using human parthenogenetic and androgenetic embryos. Human embryos have a larger portion of genome with parentally specific epigenetic states than mouse embryos. The allelic patterns of epigenetic states for orthologous regions are not conserved between humans and mice. Nevertheless, it is conserved that maternal DNA methylation and paternal H3K27me3 are associated with the repression of two alleles in humans and mice. In addition, for DNA-methylation-dependent imprinting, we report 19 novel imprinted genes and their associated germline differentially methylated regions. Unlike in mice, H3K27me3-dependent imprinting is not observed in human early embryos. Collectively, allele-specific epigenomic reprogramming is different in humans and mice.

Exploratory research on the probable shared molecular mechanism and transcription factors between chronic periodontitis and chronic obstructive pulmonary disease.

OBJECTIVES: To investigate possible cross-talk genes, associated pathways, and transcription factors between chronic periodontitis (CP) and chronic obstructive pulmonary disease (COPD). METHODS: The gene expression profiles of CP (GSE10334 and GSE16134) and COPD (GSE76925) were downloaded from the GEO database. Differential expression and functional clustering analyses were performed. The protein­protein interaction (PPI) network was constructed. The core cross-talk genes were filtered using four topological analysis algorithms and modular segmentation. Then, functional clustering analysis was performed again. RESULTS: GSE10334 detected 164 differentially expressed genes (DEGs) (119 upregulated and 45 downregulated). GSE16134 identified 208 DEGs (154 upregulated and 54 downregulated). GSE76925 identified 1 408 DEGs (557 upregulated and 851 downregulated). The PPI network included 21 nodes and 20 edges. The final screening included seven cross-talk genes: CD79A, FCRLA, CD19, IRF4, CD27, SELL, and CXCL13. Relevant pathways included primary immunodeficiency, the B-cell receptor signaling pathway, and cytokine-cytokine receptor interaction. CONCLUSIONS: This study indicates the probability of shared pathophysiology between CP and COPD, and their cross-talk genes, associated pathways, and transcription factors may offer novel concepts for future mechanistic investigations.

Comparisons of coagulation characteristics between elderly and non-elderly patients with sepsis: A prospective study.

BACKGROUND: A blunt host defense response in older patients may contribute to different coagulation responses during sepsis. We aimed to investigate the differences in coagulation parameters between elderly and non-elderly patients with sepsis. METHODS: Adult patients diagnosed with sepsis within 24 hours after admission to the intensive care unit between September 2018 and December 2020 were prospectively enrolled. Patients were categorized into the adult (18-64 years) and elderly (age ≥65 years) groups. Conventional coagulation parameters and inflammatory markers were measured on intensive care unit admission and on Days 3 and 7. Thromboelastography was performed on intensive care unit admission. The differences in the coagulation parameters between the 2 groups were evaluated. The adult and elderly patients were matched to adjust for baseline characteristics. Correlations between inflammatory markers and coagulation-related parameters were also analyzed. RESULTS: Of the 567 patients, 303 (53.4%) were elderly. Compared with adult patients, elderly patients had lower prothrombin time elevation, lower fibrinogen, D-dimer, and fibrin/Fib degradation product levels, and lower proportion of disseminated intravascular coagulation on intensive care unit admission; and, they had lower dynamic platelet, lower fibrinogen, and D-dimer levels during the first week in the intensive care unit. Thromboelastography parameters were generally within the normal range, although elderly patients had lower R and K values and a higher alpha angle. Comparisons of coagulation parameters between the 2 groups revealed similar results in the matched cohort. The inflammatory markers correlated with prothrombin time, activated partial thromboplastin time, and antithrombin III. CONCLUSION: Elderly patients had milder coagulation activation, accompanied by a decreased inflammatory response during sepsis, compared to non-elderly patients.

Remodeling of maternal mRNA through poly(A) tail orchestrates human oocyte-to-embryo transition.

Poly(A)-tail-mediated post-transcriptional regulation of maternal mRNAs is vital in the oocyte-to-embryo transition (OET). Nothing is known about poly(A) tail dynamics during the human OET. Here, we show that poly(A) tail length and internal non-A residues are highly dynamic during the human OET, using poly(A)-inclusive RNA isoform sequencing (PAIso-seq). Unexpectedly, maternal mRNAs undergo global remodeling: after deadenylation or partial degradation into 3'-UTRs, they are re-polyadenylated to produce polyadenylated degradation intermediates, coinciding with massive incorporation of non-A residues, particularly internal long consecutive U residues, into the newly synthesized poly(A) tails. Moreover, TUT4 and TUT7 contribute to the incorporation of these U residues, BTG4-mediated deadenylation produces substrates for maternal mRNA re-polyadenylation, and TENT4A and TENT4B incorporate internal G residues. The maternal mRNA remodeling is further confirmed using PAIso-seq2. Importantly, maternal mRNA remodeling is essential for the first cleavage of human embryos. Together, these findings broaden our understanding of the post-transcriptional regulation of maternal mRNAs during the human OET.

Human zygotic genome activation is initiated from paternal genome.

Although parental genomes undergo extensive epigenetic reprogramming to be equalized after fertilization, whether they play different roles in human zygotic genome activation (ZGA) remains unknown. Here, we mapped parental transcriptomes by using human parthenogenetic (PG) and androgenetic (AG) embryos during ZGA. Our data show that human ZGA is launched at the 8-cell stage in AG and bi-parental embryos, but at the morula stage in PG embryos. In contrast, mouse ZGA occurs at the same stage in PG and AG embryos. Mechanistically, primate-specific ZNF675 with AG-specific expression plays a role in human ZGA initiated from paternal genome at the 8-cell stage. AG-specifically expressed LSM1 is also critical for human maternal RNA degradation (MRD) and ZGA. The allelic expressions of ZNF675 and LSM1 are associated with their allelically epigenetic states. Notably, the paternally specific expressions of ZNF675 and LSM1 are also observed in diploid embryos. Collectively, human ZGA is initiated from paternal genome.

Dynamics of histone acetylation during human early embryogenesis.

It remains poorly understood about the regulation of gene and transposon transcription during human early embryogenesis. Here, we report that broad H3K27ac domains are genome-widely distributed in human 2-cell and 4-cell embryos and transit into typical peaks in the 8-cell embryos. The broad H3K27ac domains in early embryos before zygotic genome activation (ZGA) are also observed in mouse. It suggests that broad H3K27ac domains play conserved functions before ZGA in mammals. Intriguingly, a large portion of broad H3K27ac domains overlap with broad H3K4me3 domains. Further investigation reveals that histone deacetylases are required for the removal or transition of broad H3K27ac domains and ZGA. After ZGA, the number of typical H3K27ac peaks is dynamic, which is associated with the stage-specific gene expression. Furthermore, P300 is important for the establishment of H3K27ac peaks and the expression of associated genes in early embryos after ZGA. Our data also indicate that H3K27ac marks active transposons in early embryos. Interestingly, H3K27ac and H3K18ac signals rather than H3K9ac signals are enriched at ERVK elements in mouse embryos after ZGA. It suggests that different types of histone acetylations exert distinct roles in the activation of transposons. In summary, H3K27ac modification undergoes extensive reprogramming during early embryo development in mammals, which is associated with the expression of genes and transposons.

Limitations of gene editing assessments in human preimplantation embryos.

Range of DNA repair in response to double-strand breaks induced in human preimplantation embryos remains uncertain due to the complexity of analyzing single- or few-cell samples. Sequencing of such minute DNA input requires a whole genome amplification that can introduce artifacts, including coverage nonuniformity, amplification biases, and allelic dropouts at the target site. We show here that, on average, 26.6% of preexisting heterozygous loci in control single blastomere samples appear as homozygous after whole genome amplification indicative of allelic dropouts. To overcome these limitations, we validate on-target modifications seen in gene edited human embryos in embryonic stem cells. We show that, in addition to frequent indel mutations, biallelic double-strand breaks can also produce large deletions at the target site. Moreover, some embryonic stem cells show copy-neutral loss of heterozygosity at the cleavage site which is likely caused by interallelic gene conversion. However, the frequency of loss of heterozygosity in embryonic stem cells is lower than in blastomeres, suggesting that allelic dropouts is a common whole genome amplification outcome limiting genotyping accuracy in human preimplantation embryos.

Complete mitochondrial genome of Episymploce splendens (Blattodea: Ectobiidae): A large intergenic spacer and lacking of two tRNA genes.

The complete mitochondrial genome of Episymploce splendens, 15,802 bp in length, was determined and annotated in this study. The mito-genome included 13 PCGs, 20 tRNAs and 2 rRNAs. Unlike most typical mito-genomes with conservative gene arrangement and exceptional economic organization, E. splendens mito-genome has two tRNAs (tRNA-Gln and tRNA-Met) absence and a long intergenic spacer sequence (93 bp) between tRNA-Val and srRNA, showing the diversified features of insect mito-genomes. This is the first report of the tRNAs deletion in blattarian mito-genomes and we supported the duplication/random loss model as the origin mechanism of the long intergenic spacer. Two Numts, Numt-1 (557 bp) and Numt-2 (975 bp) transferred to the nucleus at about 14.15 Ma to 22.34 Ma, and 19.19 Ma to 24.06 Ma respectively, were found in E. splendens. They can be used as molecular fossils in insect phylogenetic relationship inference. Our study provided useful data for further studies on the evolution of insect mito-genome.

Translatome and transcriptome co-profiling reveals a role of TPRXs in human zygotic genome activation.

Translational regulation plays a critical role during the oocyte-to-embryo transition (OET) and zygotic genome activation (ZGA). Here, we integrated ultra-low-input ribosome profiling (Ribo-lite) with messenger RNA sequencing to co-profile the translatome and transcriptome in human oocytes and early embryos. Comparison with mouse counterparts identified widespread differentially translated gene functioning in epigenetic reprogramming, transposon defense, and small RNA biogenesis, in part driven by species-specific regulatory elements in 3' untranslated regions. Moreover, PRD-like homeobox transcription factors, including TPRXL, TPRX1, and TPRX2, are highly translated around ZGA. TPRX1/2/L knockdown leads to defective ZGA and preimplantation development. Ectopically expressed TPRXs bind and activate key ZGA genes in human embryonic stem cells. These data reveal the conservation and divergence of translation landscapes during OET and identify critical regulators of human ZGA.