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Cell Biology International Oct 2023Unfertilized eggs of animals contain maternal messenger RNAs (mRNAs) and proteins, which are required for the maintenance of metabolism and regulation of development... (Review)
Review
Unfertilized eggs of animals contain maternal messenger RNAs (mRNAs) and proteins, which are required for the maintenance of metabolism and regulation of development during the initial stages of embryogenesis. Unfertilized eggs are transcriptionally and translationally quiescent. After fertilization, activated translation of maternal mRNAs is one of the major forces that direct the early stages of embryogenesis before activation of the zygotic genome. However, a low rate and level of protein synthesis have been detected in unfertilized sea urchin eggs indicating that translation is not completely inhibited. Analysis of translatomes of unfertilized eggs and early embryos detected three sets of maternal mRNAs translated either before or after fertilization, or both before and after fertilization. Proteins encoded by maternal mRNAs, which are translated in unfertilized eggs, perform many different functions required for homeostasis, fertilization, egg activation, and early development. This suggests that translation in unfertilized sea urchin eggs may be required to renew the pool of proteins involved in these processes. Thus, translation may be necessary to maintain the fertility and developmental potential of sea urchin eggs during the long-term storage of eggs in ovaries until spawning begins.
Topics: Animals; Fertilization; Proteins; Ovum; Sea Urchins
PubMed: 37422860
DOI: 10.1002/cbin.12068 -
Nature Communications Dec 2023Developing synchronous bilateral Wilms tumor suggests an underlying (epi)genetic predisposition. Here, we evaluate this predisposition in 68 patients using whole exome...
Developing synchronous bilateral Wilms tumor suggests an underlying (epi)genetic predisposition. Here, we evaluate this predisposition in 68 patients using whole exome or genome sequencing (n = 85 tumors from 61 patients with matched germline blood DNA), RNA-seq (n = 99 tumors), and DNA methylation analysis (n = 61 peripheral blood, n = 29 non-diseased kidney, n = 99 tumors). We determine the predominant events for bilateral Wilms tumor predisposition: 1)pre-zygotic germline genetic variants readily detectable in blood DNA [WT1 (14.8%), NYNRIN (6.6%), TRIM28 (5%), and BRCA-related genes (5%)] or 2)post-zygotic epigenetic hypermethylation at 11p15.5 H19/ICR1 that may require analysis of multiple tissue types for diagnosis. Of 99 total tumor specimens, 16 (16.1%) have 11p15.5 normal retention of imprinting, 25 (25.2%) have 11p15.5 copy neutral loss of heterozygosity, and 58 (58.6%) have 11p15.5 H19/ICR1 epigenetic hypermethylation (loss of imprinting). Here, we ascertain the epigenetic and genetic modes of bilateral Wilms tumor predisposition.
Topics: Child; Humans; Wilms Tumor; Genotype; DNA Methylation; DNA; Kidney Neoplasms; Epigenesis, Genetic; Genomic Imprinting
PubMed: 38110397
DOI: 10.1038/s41467-023-43730-0 -
Theriogenology Jan 2024The mammalian zygote, formed after a sperm fertilizes an egg, undergoes several rounds of mitosis and morphogenesis to form the blastocyst. During the peri-implantation... (Review)
Review
The mammalian zygote, formed after a sperm fertilizes an egg, undergoes several rounds of mitosis and morphogenesis to form the blastocyst. During the peri-implantation period, the blastocyst hatches out of the zona pellucida (ZP) and invades the receptive uterine endometrium. This process promotes maternal-fetal dialogue at the physiological and molecular level, thereby initiating the implantation process. Blastocyst hatching is a consequence of elevated osmotic pressure due to active Na/K ion transporter in the blastocyst cavity, as well as proteases produced by trophectoderm (TE) that hydrolyze the ZP. This review summarizes the process underpinning blastocyst hatching, such as the hatching schedule, the location of TEs during initial hatching out of the ZP, the molecules involved in blastocyst hatching, and how these processes affect implantation events. Additionally, we focus on identifying crucial molecules that may influence the quality of implantation and predict the outcome of embryo implantation. Further understanding the mechanism of these molecules may help us to improve the efficiency of Assisted reproductive technology (ART) in livestock breeding. This review provides insight into embryonic development, specifically during the short-term process of blastocyst hatching and its effects on the following implantation.
Topics: Pregnancy; Female; Male; Animals; Semen; Embryo Implantation; Embryonic Development; Parturition; Blastocyst; Zona Pellucida; Mammals
PubMed: 37857152
DOI: 10.1016/j.theriogenology.2023.10.011 -
Zygote (Cambridge, England) Oct 2023Wagyu bulls are known to have a highly exacerbated libido, as shown by the intense sexual interest of young calves. Therefore we believe that Wagyu male animals have...
Wagyu bulls are known to have a highly exacerbated libido, as shown by the intense sexual interest of young calves. Therefore we believe that Wagyu male animals have specialized Sertoli and Leydig cells that are directly involved with the sexual precocity in this breed as mature bulls have a small scrotal circumference. This study aimed to evaluate whether there were differences in the hormone and sperm characteristics of Wagyu bulls compared with the same characteristics of subspecies and sires. Frozen-thawed semen from Wagyu, Nellore, and Angus sires were analyzed for sperm kinetics (computer-assisted sperm analysis), plasma membrane integrity, chromatin integrity, acrosome status, mitochondrial activity, lipid peroxidation and hormone [luteinizing hormone (LH) and testosterone] serum concentration. The results showed that Wagyu had lower total motility and an increased number of sperm with no motility when compared with Nellore and Angus bulls. Wagyu breed did not differ from those breeds when considering plasma and acrosome membranes integrity, mitochondrial potential, chromatin resistance, sperm lipid peroxidation or hormone (LH and testosterone) concentrations. We concluded that Wagyu sires had lower total motility when compared with Nellore and Angus bulls. Wagyu breed did not differ from these breeds when considering plasma and acrosome membranes integrity, mitochondrial potential, chromatin resistance, sperm lipid peroxidation, or hormone (LH and testosterone) concentrations.
Topics: Male; Cattle; Animals; Semen; Sperm Count; Sperm Motility; Spermatozoa; Testosterone; Chromatin
PubMed: 37492001
DOI: 10.1017/S0967199423000278 -
ELife Jul 2023Sex-specific splicing is an essential process that regulates sex determination and drives sexual dimorphism. Yet, how early in development widespread sex-specific...
Sex-specific splicing is an essential process that regulates sex determination and drives sexual dimorphism. Yet, how early in development widespread sex-specific transcript diversity occurs was unknown because it had yet to be studied at the genome-wide level. We use the powerful model to show that widespread sex-specific transcript diversity occurs early in development, concurrent with zygotic genome activation. We also present a new pipeline called time2Splice to quantify changes in alternative splicing over time. Furthermore, we determine that one of the consequences of losing an essential maternally deposited pioneer factor called CLAMP (chromatin-linked adapter for MSL proteins) is altered sex-specific splicing of genes involved in diverse biological processes that drive development. Overall, we show that sex-specific differences in transcript diversity exist even at the earliest stages of development..
Topics: Animals; Male; Female; Drosophila; Drosophila melanogaster; Drosophila Proteins; Embryonic Development; Genome; Alternative Splicing
PubMed: 37466240
DOI: 10.7554/eLife.87865 -
Fertility and Sterility Oct 2023To examine the developmental competence of immature oocytes in stimulated cycles, that matured after rescue in vitro maturation (IVM) compared with their sibling...
OBJECTIVE
To examine the developmental competence of immature oocytes in stimulated cycles, that matured after rescue in vitro maturation (IVM) compared with their sibling in vivo matured oocytes.
DESIGN
Retrospective cohort study.
SETTING
IVF clinic.
PATIENTS
A total of 182 patients underwent 200 controlled ovarian stimulation cycles with intracytoplasmic sperm injection cycles in which immature oocytes were retrieved and at least one mature oocyte was obtained through rescue IVM.
INTERVENTION
In vitro culture of immature germinal vesicle (GV) and metaphase I (MI) oocytes, retrieved in stimulated cycles.
MAIN OUTCOME MEASURES
Fertilization rate, cleavage rate, blastulation rate, ploidy of embryos evaluated using preimplantation genetic testing for aneuploidy, morphokinetic parameters and pregnancy outcomes.
RESULTS
In total, 2,288 oocytes were retrieved from 200 cycles. After denudation, 1,056 of the oocytes (46% ± 16%) were classified as metaphase II (MII). A total of 333/375 (89%) of MI oocytes and 292/540 (54%) of GV oocytes matured overnight and underwent intracytoplasmic sperm injection. The fertilization rates of matured oocytes from MI rescue IVM (R-MI) and from GV rescue IVM (R-GV) were comparable with those of their sibling MII oocytes (71% vs. 66%; 66% vs. 63%, respectively). Early cleavage rates (80% ± 35% vs. 92% ± 20%; 80% ± 42% vs. 95% ± 28%, respectively) and blastulation rates (32 ± 40% vs. 62 ± 33%; 24 ± 37% vs. 60 ± 35%, respectively) were significantly decreased in rescue IVM matured oocytes (R-oocytes)-derived zygotes, but the blastocyst (BL) euploidy rate and "good quality" BL rate were comparable with those of MII sibling-derived embryos. In addition, rescue IVM embryos showed significantly higher levels of multinucleation at the 2- and 4-cell stages, as well as higher rates of zygote direct cleavage from one to 3 to 4 cells. Overall, 21 transfers of rescue IVM embryos resulted in 3 healthy live births.
CONCLUSIONS
For patients with a low maturation rate and/or low numbers of mature oocytes at retrieval, rescue IVM may contribute more competent oocytes and additional viable BLs for transfer from the same stimulation cycle, maximizing the chances for pregnancy and live birth.
Topics: Pregnancy; Female; Humans; Male; In Vitro Oocyte Maturation Techniques; Retrospective Studies; Semen; Oocytes; Pregnancy Outcome; Fertilization in Vitro
PubMed: 37257719
DOI: 10.1016/j.fertnstert.2023.05.163 -
Cell Reports Sep 2023The transcription factor DUX4 regulates a portion of the zygotic gene activation (ZGA) program in the early embryo. Many cancers express DUX4 but it is unknown whether...
The transcription factor DUX4 regulates a portion of the zygotic gene activation (ZGA) program in the early embryo. Many cancers express DUX4 but it is unknown whether this generates cells similar to early embryonic stem cells. Here we identified cancer cell lines that express DUX4 and showed that DUX4 is transiently expressed in a small subset of the cells. DUX4 expression activates the DUX4-regulated ZGA transcriptional program, the subsequent 8C-like program, and markers of early embryonic lineages, while suppressing steady-state and interferon-induced MHC class I expression. Although DUX4 was expressed in a small number of cells under standard culture conditions, DNA damage or changes in growth conditions increased the fraction of cells expressing DUX4 and its downstream programs. Our demonstration that transient expression of endogenous DUX4 in cancer cells induces a metastable early embryonic stem cell program and suppresses antigen presentation has implications for cancer growth, progression, and immune evasion.
Topics: Humans; Cell Line; Genes, Homeobox; Homeodomain Proteins; Muscular Dystrophy, Facioscapulohumeral; Neoplasms; Transcription Factors; Zygote
PubMed: 37691147
DOI: 10.1016/j.celrep.2023.113114 -
Genes & Development Oct 2023Fertilization in mammals is accompanied by an intense period of chromatin remodeling and major changes in nuclear organization. How the earliest events in embryogenesis,...
Fertilization in mammals is accompanied by an intense period of chromatin remodeling and major changes in nuclear organization. How the earliest events in embryogenesis, including zygotic genome activation (ZGA) during maternal-to-zygotic transition, influence such remodeling remains unknown. Here, we have investigated the establishment of nuclear architecture, focusing on the remodeling of lamina-associated domains (LADs) during this transition. We report that LADs reorganize gradually in two-cell embryos and that blocking ZGA leads to major changes in nuclear organization, including altered chromatin and genomic features of LADs and redistribution of H3K4me3 toward the nuclear lamina. Our data indicate that the rearrangement of LADs is an integral component of the maternal-to-zygotic transition and that transcription contributes to shaping nuclear organization at the beginning of mammalian development.
Topics: Animals; Mice; RNA Polymerase II; Transcription, Genetic; Embryonic Development; Zygote; Mammals; Gene Expression Regulation, Developmental; Chromatin
PubMed: 37914351
DOI: 10.1101/gad.350799.123 -
Zygote (Cambridge, England) Oct 2023Since the birth of the first baby by fertilization in 1978, more than 9 million children have been born worldwide using medically assisted reproductive treatments.... (Review)
Review
Since the birth of the first baby by fertilization in 1978, more than 9 million children have been born worldwide using medically assisted reproductive treatments. Fertilization naturally takes place in the maternal oviduct where unique physiological conditions enable the early healthy development of the embryo. During this dynamic period of early development major waves of epigenetic reprogramming, crucial for the normal fate of the embryo, take place. Increasingly, over the past 20 years concerns relating to the increased incidence of epigenetic anomalies in general, and genomic-imprinting disorders in particular, have been raised following assisted reproduction technology (ART) treatments. Epigenetic reprogramming is particularly susceptible to environmental conditions during the periconceptional period and non-physiological conditions such as ovarian stimulation, fertilization and embryo culture, as well as cryopreservation procedure, might have the potential to independently or collectively contribute to epigenetic dysregulation. Therefore, this narrative review offers a critical reappraisal of the evidence relating to the association between embryo cryopreservation and potential epigenetic regulation and the consequences on gene expression together with long-term consequences for offspring health and wellbeing. Current literature suggests that epigenetic and transcriptomic profiles are sensitive to the stress induced by vitrification, in terms of osmotic shock, temperature and pH changes, and toxicity of cryoprotectants, it is therefore, critical to have a more comprehensive understanding and recognition of potential unanticipated iatrogenic-induced perturbations of epigenetic modifications that may or may not be a consequence of vitrification.
Topics: Child; Humans; Epigenesis, Genetic; Reproductive Techniques, Assisted; Cryopreservation; Fertilization in Vitro; Genomic Imprinting
PubMed: 37409505
DOI: 10.1017/S0967199423000345 -
Journal of Assisted Reproduction and... Nov 2023The prevailing assumption has been that the human spermatozoon provides only one centriole to the zygote: the proximal centriole, with a canonical, cylinder-like shape.... (Review)
Review
The prevailing assumption has been that the human spermatozoon provides only one centriole to the zygote: the proximal centriole, with a canonical, cylinder-like shape. This overly simplistic view has come under challenge since discovering that the human spermatozoon provides a second, atypical centriole to the zygote. The study of human zygotes is challenging for ethical reasons, and bovine zygotes provide an important model due to a similarity in centrosome embryonic inherence and function. Detailed ultrastructural analyses by Uzbekov and colleagues identify the persistence of atypical centrioles in bovine early embryos, raising questions about the original single-centriole model. Whether the parental origin of nascent atypical centrioles or their wide structural diversity and deviation from the canonical centriolar form in blastomeres constitutes sufficient evidence to warrant a reconsideration of the single-centriole model is discussed herein. Because previous human studies identified only one canonical centriole in the zygote, atypical centrioles are likely present in the early human embryo; therefore, it is time to rethink the role of paternal centrioles in human development.
Topics: Male; Humans; Animals; Cattle; Centrioles; Spermatozoa; Centrosome; Zygote; Embryonic Development; Mammals
PubMed: 37713143
DOI: 10.1007/s10815-023-02927-4