How do transcriptomics vary in haploid human androgenote embryos at single cell level in the first four cell cycles of embryo development?
Gene expression peaks at the fourth cell cycle, however some ...androcytes exhibit unique transcriptional behaviors.
The developmental potential of an embryo is determined by the competence of the oocyte and the sperm. However, studies of the contribution of the paternal genome using pure haploid androgenotes are very scarce.
This study was performed analyzing the single-cell transcriptomic sequencing of 38 androcytes obtained from 10 androgenote bioconstructs previously produced in vitro (de Castro et al., 2023). These results were analyzed through different bioinformatics software such as g: Profiler, GSEA, Cytoscape, and Reactome.
Single cell sequencing was used to obtain the transcriptomic profiles of the different androcytes. The results obtained were compared between the different cycles studied using the DESeq2 program and functional enrichment pathways using g: Profiler, Cytoscape, and Reactome.
A wave of paternally driven transcriptomic activation was found during the third-cell cycle, with 1128 upregulated and 225 downregulated genes and the fourth-cell cycle, with 1373 upregulated and 286 downregulated genes, compared to first-cell cycle androcytes. Differentially expressed routes related to cell differentiation, DNA-binding transcription, RNA biosynthesis and RNA polymerase II transcription regulatory complex, and cell death were found in the third and fourth with respect to the first-cell cycle. Conversely, in the fourth cell cycle, 153 downregulated and 332 upregulated genes were found compared with third cell cycle, associated with differentially expressed processes related to E-box binding and zinc finger protein 652 (ZNF652) transcription factor. Further, significant overexpression of LEUTX, PRAMEF1, DUXA, RFPL4A, TRIM43, and ZNF675 found in androgenotes, compared to biparental embryos, highlights the paternal contributions to zygote genome activation.
All raw sequencing data are available through the Gene Expression Omnibus (GEO) under accessions number: GSE216501.
Extrapolation of biological events from uniparental constructs to biparental embryos should be done with caution. Maternal and paternal genomes do not act independently of each other in a natural condition. The absence of one genome may affect gene transcription of the other. In this sense, the haploid condition of the bioconstructs could mask the transcriptomic patterns of the single cells.
The results obtained demonstrated the level of involvement of the human paternal haploid genome in the early stages of embryo development as well as its evolution at the transcriptomic level, laying the groundwork for the use of these bioconstructs as reliable models to dispel doubts about the genetic role played by the paternal genome in the early cycles of embryo development.
This study was funded by Instituto de Salud Carlos III (ISCIII) through the project 'PI22/00924', co-funded by European Regional Development Fund (ERDF); 'A way to make Europe'. F.D. was supported by the Spanish Ministry of Economy and Competitiveness through the Miguel Servet program (CPII018/00002). M.J.E. was supported by Instituto de Salud Carlos III (PI19/00577 M.J.E.) and FI20/00086. P.dC. was supported by a predoctoral grant for training in research into health (PFIS PI19/00577) from the Instituto de Salud Carlos III. All authors declare having no conflict of interest with regard to this trial.
STUDY QUESTION
Does female obesity affect the dynamic parameters of embryo quality assessed by time-lapse analysis?
SUMMARY ANSWER
Female obesity does not affect the dynamic embryo quality as ...determined by image acquisition and time-lapse analysis.
WHAT IS KNOWN ALREADY
Female obesity impairs natural and assisted reproduction but there is no agreement on the specific contribution of gametes, embryos or endometrial receptivity. In this preliminary study the dynamic parameters of embryo quality are assessed for the first time by time-lapse analysis.
STUDY DESIGN, SIZE, DURATION
Two-year cohort retrospective study comparing embryos from three groups of patients according to the presence of infertility and/or obesity.
PARTICIPANTS AND SETTING
Participants attended a University-affiliated private clinic where ICSI was performed. Using an IVF incubator with a built-in camera designed to automatically acquire images at defined time points, we monitored individual embryos from 89 patients: 71 embryos from 13 obese infertile women, 242 embryos from 45 normoweight infertile women and 111 embryos from 31 normoweight fertile oocyte donors. The chronological pattern of cell divisions (timings of cell cleavages) and other morphologic features (time-dependent cell size and nucleation) was recorded.
MAIN RESULTS AND THE ROLE OF CHANCE
Embryos from obese and normoweight infertile women showed similar cleavage patterns, but occurring more slowly, to those from fertile donors. These differences were statistically significant for t2 (time of cleavage to two-blastomere embryo) (P = 0.016), t3 (P = 0.014), t4 (P = 0.003) and t5 (P = 0.040).
LIMITATIONS, REASONS FOR CAUTION
These are preliminary data from a retrospective analysis with a limited sample size.
GENERALIZABILITY TO OTHER POPULATIONS
Not recommended until further studies using time-lapse analysis of a larger sample have been performed.
STUDY FUNDING/COMPETING INTEREST(S)
None.
The Rift Valley fever virus (RVFV) is transmitted by infected mosquitoes, causing severe disease in humans and livestock across Africa. We determined the x-ray structure of the RVFV class II fusion ...protein Gc in its postfusion form and in complex with a glycerophospholipid (GPL) bound in a conserved cavity next to the fusion loop. Site-directed mutagenesis and molecular dynamics simulations further revealed a built-in motif allowing en bloc insertion of the fusion loop into membranes, making few nonpolar side-chain interactions with the aliphatic moiety and multiple polar interactions with lipid head groups upon membrane restructuring. The GPL head-group recognition pocket is conserved in the fusion proteins of other arthropod-borne viruses, such as Zika and chikungunya viruses, which have recently caused major epidemics worldwide.
How can laboratory and clinical outcomes of spontaneously, early maturing germinal-vesicle oocytes and sibling in-vivo-matured (metaphase II MII) oocytes be quantified and compared?
A prospective, ...non-randomized intra-cohort study of oocytes from women aged 38 years or younger, with six or fewer MII oocytes and four or more germinal vesicles retrieved. No indication was identified for genetic tests or oocyte or embryo cryopreservation. The study was carried out at IVIRMA-Valencia. Early maturing germinal vesicles were selected for reproductive purposes. In vitro- and in-vivo MII oocytes were fertilized. After time-lapse culture, hatching blastocysts from germinal vesicles were biopsied for aneuploidy screening and vitrified. Laboratory and clinical outcomes were compared according to oocyte origin.
Almost 70% of germinal vesicles had matured early and spontaneously, and had comparable in vitro-outcomes and morphokinetics to sibling in vivo-matured oocytes. Fifty per cent of biopsied blastocysts were euploid. Germinal-vesicle rescue increased the number of MII oocytes per cycle to 3.9, finally adding one extra-blastocyst per cycle. A live birth confirmed the feasibility of this approach. Further data, however, are needed to quantify its real contribution to standard intracytoplasmic sperm injection cycles. Nevertheless, 40% of patients obtained either an immediate advantage (reduction of cancellation rate) or long-term benefit (availability of extra blastocysts of attempts).
Germinal-vesicle rescue can be considered as a complementary approach when folliculometry (expected) and number of MII (observed) are unequal.
Jets at the LHC are expected to provide the testing ground for studying QCD energy loss. In this contribution, we briefly outline the strategy that will be used to measure jets in ATLAS and how we ...will go about studying energy loss. We describe the utility of measuring the jet
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, the fragmentation function, and heavy flavor jets. Utilizing the collision energy provided by the LHC and the nearly hermetic and highly segmented calorimeter, ATLAS is expected to make important contributions to the understanding of parton energy loss using fully reconstructed jets.
sPHENIX is a new experiment under construction for the Relativistic Heavy Ion Collider at Brookhaven National Laboratory which will study the quark-gluon plasma to further the understanding of ...quantum chromodynamics (QCP) matter and interactions. A prototype of the sPHENIX electromagnetic calorimeter (EMCal) was tested at the Fermilab Test Beam Facility in Spring 2018 as experiment T-1044. The EMCal prototype corresponds to a solid angle of <inline-formula> <tex-math notation="LaTeX">\Delta \eta \times \Delta \phi = 0.2 \times 0.2 </tex-math></inline-formula> centered at pseudo-rapidity <inline-formula> <tex-math notation="LaTeX">\eta = 1 </tex-math></inline-formula>. The prototype consists of scintillating fibers embedded in a mix of tungsten powder and epoxy. The fibers project back approximately to the center of the sPHENIX detector, giving 2-D projectivity. The energy response of the EMCal prototype was studied as a function of position and input energy. The energy resolution of the EMCal prototype was obtained after applying a position-dependent energy correction and a beam profile correction. Two separate position-dependent corrections were considered. The EMCal energy resolution was found to be <inline-formula> <tex-math notation="LaTeX">\sigma (E)/\langle E\rangle = 3.5(0.1) \oplus 13.3(0.2)/\sqrt {E} </tex-math></inline-formula> based on the hodoscope position-dependent correction, and <inline-formula> <tex-math notation="LaTeX">\sigma (E)/\langle E\rangle = 3.0(0.1) \oplus 15.4(0.3)/\sqrt {E} </tex-math></inline-formula> based on the cluster position-dependent correction. These energy resolution results meet the requirements of the sPHENIX physics program.
Occupational mutual insurance companies (OMICs), in collaboration with the Spanish Social Security System, provide healthcare and manage the economic benefits for the workers in Spain. They have ...ambulatory care centers that attend outpatient trauma pathology, although most of the studies published have focused on surgical and hospital activity. The aim of this study was to detect adverse events (AEs) in outpatient trauma care in the context of an OMIC.
A cohort study designed to identify harmful safety incidents (adverse events, AEs) in 2017 was conducted. A random sample of 313 medical records among patients who were visited more than 3 medical and nursing attendances during their outpatient process. The AEs detected were classified according to category, severity and preventability.
We identified 48 AEs (15.3% of medical records, 95% CI 11.3-19.3), most of them procedure-related, while 27 (56.2%) were preventable and 46 mild (95.8%).
The AEs identified are double than those found in primary care general consultations in Spain and are close to the lower range of studies on surgical AEs in traumatology and orthopedics. Preventable AEs were within expected limits. Over half of AEs are preventable, within that group, the mild AEs have an increased rate of preventability. These results highlight the relevance of research of patient safety in the outpatient care of trauma and orthopaedic procedures in an OMIC for patient safety and contribute to introduce improvements in outpatient care.
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