-
Journal of Assisted Reproduction and... Dec 2023Infertility remains a human health burden globally. Only a fraction of embryos produced via assisted reproductive technologies (ARTs) develop to the blastocyst stage in...
PURPOSE
Infertility remains a human health burden globally. Only a fraction of embryos produced via assisted reproductive technologies (ARTs) develop to the blastocyst stage in vitro. lncRNA abundance changes significantly during human early embryonic development, indicating vital regulatory roles of lncRNAs in this process. The aim of this study is to obtain insights into the transcriptional basis of developmental events.
METHODS
scRNA-seq data and SUPeR-seq data were used to investigate the lncRNA profiles of human preimplantation embryos. The top 50 highly expressed unique and shared lncRNAs in each stage of preimplantation development were identified. Comparative analysis of the two datasets was used to verify the consistent expression patterns of the lncRNAs. Differentially expressed lncRNAs were identified and subjected to functional enrichment analysis.
RESULTS
The lncRNA profiles of human preimplantation embryos in the E-MTAB-3929 dataset were similar to those in the GSE71318 dataset. The ratios of overlap among the top 50 highly expressed lncRNAs between two pairs of stages (2-cell stage vs. 4-cell stage and 8-cell stage vs. morula) were aberrantly low compared with those between other stages. Each stage of preimplantation development exhibited unique and shared lncRNAs among the top 50 highly expressed lncRNAs. Among the between-group comparisons, the 2-cell stage vs. 4-cell stage showed the highest number of differentially expressed lncRNAs. Functional enrichment analysis revealed that differentially expressed lncRNAs and their associated super enhancers and RNA binding proteins (RBPs) are closely involved in regulating embryonic development. These lncRNAs could function as important cell markers for distinguishing fetal germ cells.
CONCLUSIONS
Our study paves the way for understanding the regulation of developmental events, which might be beneficial for improved reproductive outcomes.
Topics: Pregnancy; Female; Humans; Transcriptome; RNA, Long Noncoding; Embryonic Development; Blastocyst; Morula; Gene Expression Profiling
PubMed: 37770818
DOI: 10.1007/s10815-023-02951-4 -
Genome Biology Jul 2023The oocyte-to-embryo transition (OET) converts terminally differentiated gametes into a totipotent embryo and is critically controlled by maternal mRNAs and proteins,...
BACKGROUND
The oocyte-to-embryo transition (OET) converts terminally differentiated gametes into a totipotent embryo and is critically controlled by maternal mRNAs and proteins, while the genome is silent until zygotic genome activation. How the transcriptome, translatome, and proteome are coordinated during this critical developmental window remains poorly understood.
RESULTS
Utilizing a highly sensitive and quantitative mass spectrometry approach, we obtain high-quality proteome data spanning seven mouse stages, from full-grown oocyte (FGO) to blastocyst, using 100 oocytes/embryos at each stage. Integrative analyses reveal distinct proteome reprogramming compared to that of the transcriptome or translatome. FGO to 8-cell proteomes are dominated by FGO-stockpiled proteins, while the transcriptome and translatome are more dynamic. FGO-originated proteins frequently persist to blastocyst while corresponding transcripts are already downregulated or decayed. Improved concordance between protein and translation or transcription is observed for genes starting translation upon meiotic resumption, as well as those transcribed and translated only in embryos. Concordance between protein and transcription/translation is also observed for proteins with short half-lives. We built a kinetic model that predicts protein dynamics by incorporating both initial protein abundance in FGOs and translation kinetics across developmental stages.
CONCLUSIONS
Through integrative analyses of datasets generated by ultrasensitive methods, our study reveals that the proteome shows distinct dynamics compared to the translatome and transcriptome during mouse OET. We propose that the remarkably stable oocyte-originated proteome may help save resources to accommodate the demanding needs of growing embryos. This study will advance our understanding of mammalian OET and the fundamental principles governing gene expression.
Topics: Animals; Mice; Proteome; Transcriptome; Embryo, Mammalian; Blastocyst; Oocytes; Gene Expression Regulation, Developmental; Mammals
PubMed: 37443062
DOI: 10.1186/s13059-023-02997-8 -
American Journal of Orthodontics and... Dec 2023Oligodontia is a serious developmental dental anomaly that requires long-term multidisciplinary treatment, but its clinical characteristics are not well understood...
INTRODUCTION
Oligodontia is a serious developmental dental anomaly that requires long-term multidisciplinary treatment, but its clinical characteristics are not well understood because it is rare. This study evaluated the mesiodistal angulation and developmental stages of unerupted mandibular second premolars (MnP2s) in orthodontic patients with nonsyndromic oligodontia.
METHODS
Thirty-seven patients with oligodontia with at least 1 unerupted MnP2 in Demirjian's developmental stages between D and G were selected. Age- and sex-matched patients without tooth agenesis, excluding third molars, were selected as the control group. Mesiodistal angulation between the long axis of the available MnP2 and the mandibular plane was measured on panoramic radiographs.
RESULTS
The MnP2 was significantly more distally angulated in the oligodontia group than in the control group. The developmental stage of the MnP2 in the oligodontia group was significantly delayed (1.04 ± 0.26 years; 95% confidence interval, 0.53-1.55 years). No correlation between the mesiodistal angulation and the developmental stage of the MnP2 was found in both groups.
CONCLUSIONS
Significant distal angulation and delayed developmental stages of MnP2s were found in patients with nonsyndromic oligodontia compared with age- and sex-matched patients without agenesis of permanent teeth, excluding third molars. However, no significant correlation was found between them. Regardless of the severity of the distal angulation of MnP2, observing delayed dental development in each patient is important.
Topics: Humans; Bicuspid; Anodontia; Molar, Third; Radiography, Panoramic; Mandible
PubMed: 37486279
DOI: 10.1016/j.ajodo.2023.05.029 -
Nature Communications Sep 2023The time that it takes the brain to develop is highly variable across animals. Although staging systems equate major developmental milestones between mammalian species,...
The time that it takes the brain to develop is highly variable across animals. Although staging systems equate major developmental milestones between mammalian species, it remains unclear how distinct processes of cortical development scale within these timeframes. Here, we compare the timing of cortical development in two mammals of similar size but different developmental pace: eutherian mice and marsupial fat-tailed dunnarts. Our results reveal that the temporal relationship between cell birth and laminar specification aligns to equivalent stages between these species, but that migration and axon extension do not scale uniformly according to the developmental stages, and are relatively more advanced in dunnarts. We identify a lack of basal intermediate progenitor cells in dunnarts that likely contributes in part to this timing difference. These findings demonstrate temporal limitations and differential plasticity of cortical developmental processes between similarly sized Therians and provide insight into subtle temporal changes that may have contributed to the early diversification of the mammalian brain.
Topics: Animals; Mice; Mammals; Marsupialia; Eutheria; Brain; Endocrine Glands
PubMed: 37741828
DOI: 10.1038/s41467-023-41652-5 -
Journal of Molecular Histology Apr 2024Cytodifferentiation of odontogenic cells, a late stage event in odontogenesis is based on gene regulation. However, studies on the identification of the involved genes... (Review)
Review
Cytodifferentiation of odontogenic cells, a late stage event in odontogenesis is based on gene regulation. However, studies on the identification of the involved genes are scarce. The present study aimed to search for molecules for the cytodifferentiation of ameloblastic cells in rats. Differential display-PCR revealed a differentially expressed gene between cap/early bell stage and hard tissue formation stage in molars. This gene was identified as N-myc Downregulated Gene 1 (Ndrg1), which is the first report in tooth development. Real time PCR and western blotting confirmed that the mRNA level of Ndrg1 was higher during enamel formation than the cap stage. Ndrg1 expression was upregulated in the early bell, crown, and root stages in a time-dependent manner. These patterns of expression were similar in Ndrg2, but Ndrg3 and Ndrg4 levels did not change during the developmental stages. Immunofluorescence revealed that strong immunoreactivity against Ndrg1 were detected in differentiated ameloblasts only, not inner enamel epithelium, odontoblasts and ameloblastic cells in defected enamel regions. Alkaline phosphatase and alizarin red s stains along with real time PCR, revealed that Ndrg1 and Ndrg2 were involved in cytodifferentiation and enamel matrix mineralization by selectively regulating amelogenin and ameloblastin genes in SF2 ameloblastic cells. These results suggest that Ndrg may play a crucial functional role in the cytodifferentiation of ameloblasts for amelogenesis.
Topics: Animals; Rats; Ameloblasts; Amelogenesis; Molar; Muscle Proteins; Nerve Tissue Proteins; Odontogenesis; Proteins
PubMed: 38407765
DOI: 10.1007/s10735-024-10182-9 -
Environmental Pollution (Barking, Essex... Nov 2023Per- and Polyfluoroalkyl Substances (PFAS) are a diverse class of industrial chemicals that have been used for decades in industrial and commercial applications. Due to...
Per- and Polyfluoroalkyl Substances (PFAS) are a diverse class of industrial chemicals that have been used for decades in industrial and commercial applications. Due to their widespread usages, persistence in the environment, and bioaccumulation in animals and humans, great public health concerns have been raised on adverse health risks of PFAS. In this study, ten PFAS were selected according to their occurrence in different water bodies. The wild-type worms were exposed to individual PFAS at 0, 0.1, 1,10, 100, and 200 μM, and the toxic effects of PFAS on growth, development, fecundity, and behavior at different life stages were investigated using a high-throughput screening (HTS) platform. Our results showed that perfluorooctanesulfonic acid (PFOS), 1H,1H, 2H, 2H-perfluorooctanesulfonamidoacetic acid (NEtFOSAA), perfluorobutanesulfonic (PFBS), and perfluorohexanesulfonic acid (PFHxS) exhibited significant inhibitive effects on the growth in the L4 larva and later stages of worms with concentrations ranging from 0.1 to 200 μmol/L. PFOS and PFBS significantly decreased the brood size of worms across all tested concentrations (p < 0.05), and the most potent PFAS is PFOS with BMC of 0.02013 μM (BMCL, 1.6e-06 μM). During adulthood, all PFAS induced a significant reduction in motility (p < 0.01), while only PFOS can significantly induce behavior alteration at the early larvae stage. Furthermore, the adverse effects occurred in larval stages were found to be the most susceptible to the PFAS exposure. These findings provide valuable insights into the potential adverse effects associated with PFAS exposure and show the importance of considering developmental stages in toxicity assessments.
Topics: Humans; Animals; Adult; Caenorhabditis elegans; Alkanesulfonic Acids; Fluorocarbons; Bioaccumulation
PubMed: 37619695
DOI: 10.1016/j.envpol.2023.122429 -
MethodsX Jun 2024Fish display diverse reproductive strategies and their gametogenesis is influenced by numerous genetic, physiological and environmental factors. The analysis of 5S rRNA...
Fish display diverse reproductive strategies and their gametogenesis is influenced by numerous genetic, physiological and environmental factors. The analysis of 5S rRNA expression levels in gonads has been proposed as useful method for the molecular identification of the presence of oocytes in fish tissues. The present method provides an easy and unbiased approach to analyse the expression of tRNAs and 5S rRNA in teleost gonads and stablish the presence and developmental stage of oocytes. Total RNA extracted from gonads is analysed through capillary electrophoresis in a Bioanalyzer 2100 (Agilent Technologies) using Small RNA Assays. Electropherograms allow quantifying the concentrations of tRNAs, 5S rRNA and 5.8S rRNA per sample and calculate their tRNA/5.8S rRNA and 5S/5.8S rRNA indices. Both indices clearly differentiate ovaries from testes and can be used to identify testes that present oocytes due to exposure to environmental xenoestrogens. The tRNA/5.8S and 5S/5.8S indices show the highest values in ovaries in previtellogenic stage, values decreasing as they advance towards maturity.•Detailed molecular method to sex fish and quantitatively identify the maturity stage of females.•tRNA levels in gonads can help in the study of teleost reproduction (female fecundity assessment, molecular gonad sexing) and environmental health assessment.
PubMed: 38192358
DOI: 10.1016/j.mex.2023.102526 -
Microbial Ecology Nov 2023Many studies have noted differences in microbes associated with animals reared in captivity compared to their wild counterparts, but few studies have examined how...
Many studies have noted differences in microbes associated with animals reared in captivity compared to their wild counterparts, but few studies have examined how microbes change when animals are reintroduced to the wild after captive rearing. As captive assurance populations and reintroduction programs increase, a better understanding of how microbial symbionts respond during animal translocations is critical. We examined changes in microbes associated with boreal toads (Anaxyrus boreas), a threatened amphibian, after reintroduction to the wild following captive rearing. Previous studies demonstrate that developmental life stage is an important factor in amphibian microbiomes. We collected 16S marker-gene sequencing datasets to investigate: (i) comparisons of the skin, mouth, and fecal bacteria of boreal toads across four developmental life stages in captivity and the wild, (ii) tadpole skin bacteria before and after reintroduction to the wild, and (iii) adult skin bacteria during reintroduction to the wild. We demonstrated that differences occur across skin, fecal, and mouth bacterial communities in captive versus wild boreal toads, and that the degree of difference depends on developmental stage. Skin bacterial communities from captive tadpoles were more similar to their wild counterparts than captive post-metamorphic individuals were to their wild counterparts. When captive-reared tadpoles were introduced to a wild site, their skin bacteria changed rapidly to resemble wild tadpoles. Similarly, the skin bacterial communities of reintroduced adult boreal toads also shifted to resemble those of wild toads. Our results indicate that a clear microbial signature of captivity in amphibians does not persist after release into natural habitat.
Topics: Humans; Animals; Bufonidae; Larva; Bacteria; Microbiota; Skin
PubMed: 37222806
DOI: 10.1007/s00248-023-02229-3 -
Nature Jun 2024The evolution of the modern human brain was accompanied by distinct molecular and cellular specializations, which underpin our diverse cognitive abilities but also... (Review)
Review
The evolution of the modern human brain was accompanied by distinct molecular and cellular specializations, which underpin our diverse cognitive abilities but also increase our susceptibility to neurological diseases. These features, some specific to humans and others shared with related species, manifest during different stages of brain development. In this multi-stage process, neural stem cells proliferate to produce a large and diverse progenitor pool, giving rise to excitatory or inhibitory neurons that integrate into circuits during further maturation. This process unfolds over varying time scales across species and has progressively become slower in the human lineage, with differences in tempo correlating with differences in brain size, cell number and diversity, and connectivity. Here we introduce the terms 'bradychrony' and 'tachycrony' to describe slowed and accelerated developmental tempos, respectively. We review how recent technical advances across disciplines, including advanced engineering of in vitro models, functional comparative genetics and high-throughput single-cell profiling, are leading to a deeper understanding of how specializations of the human brain arise during bradychronic neurodevelopment. Emerging insights point to a central role for genetics, gene-regulatory networks, cellular innovations and developmental tempo, which together contribute to the establishment of human specializations during various stages of neurodevelopment and at different points in evolution.
Topics: Humans; Brain; Biological Evolution; Animals; Neural Stem Cells; Neurogenesis; Time Factors; Neurons; Single-Cell Analysis; Gene Regulatory Networks
PubMed: 38898293
DOI: 10.1038/s41586-024-07521-x -
Current Opinion in Hematology May 2024Recent work reveals that cell cycle duration and structure are remodeled in lock-step with distinct stages of erythroid differentiation. These cell cycle features have... (Review)
Review
PURPOSE OF REVIEW
Recent work reveals that cell cycle duration and structure are remodeled in lock-step with distinct stages of erythroid differentiation. These cell cycle features have regulatory roles in differentiation, beyond the generic function of increasing cell number.
RECENT FINDINGS
Developmental progression through the early erythroid progenitor stage (known as colony-forming-erythroid, or 'CFU-e') is characterized by gradual shortening of G1 phase of the cycle. This process culminates in a key transcriptional switch to erythroid terminal differentiation (ETD) that is synchronized with, and dependent on, S phase progression. Further, the CFU-e/ETD switch takes place during an unusually short S phase, part of an exceptionally short cell cycle that is characterized by globally fast replication fork speeds. Cell cycle and S phase speed can alter developmental events during erythroid differentiation, through pathways that are targeted by glucocorticoid and erythropoietin signaling during the erythroid stress response.
SUMMARY
There is close inter-dependence between cell cycle structure and duration, S phase and replication fork speeds, and erythroid differentiation stage. Further, modulation of cell cycle structure and speed cycle impacts developmental progression and cell fate decisions during erythroid differentiation. These pathways may offer novel mechanistic insights and potential therapeutic targets.
Topics: Humans; Cell Cycle; Cell Differentiation; Erythroid Precursor Cells; S Phase; Signal Transduction; Erythropoiesis
PubMed: 38415760
DOI: 10.1097/MOH.0000000000000811