12 results on '"Human embryo"'
Search Results
2. Microarray evidence that 8-cell human embryos express some hormone family members including oxytocin.
- Author
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Harris AL, Dinopoulou V, Loutradis D, Drakakis P, and Kiessling AA
- Subjects
- Female, Humans, Embryo, Mammalian, Microarray Analysis, Steroids metabolism, Oxytocin genetics, Oxytocin metabolism, Fibroblasts metabolism
- Abstract
Objective: This study is to discover hormone pathways active in early cleaving human embryos., Methods: A list of 152 hormones and receptors were compiled to query the microarray database of mRNAs in 8-cell human embryos, two lines of human embryonic stem cells plus human fibroblasts before and after induced pluripotency., Results: Over half of the 152 hormones and receptors were silent on the arrays of all cell types, and more were detected at high or moderate levels on the 8-cell arrays than on the pluripotent cell or fibroblast arrays. Eight hormone family genes were uniquely detected at least 22-fold higher on the 8-cell arrays than the stem cell arrays: AVPI1, CCK, CORT, FSTL4, GIP, GPHA2, OXT, and PPY suggesting novel roles for these proteins in early development. Oxytocin was detected by pilot immunoassay in culture media collected from Day 3 embryos. Robust detection of CRHR1 and EPOR suggests the 8-cell embryo may be responsive to maternal CRH and EPO. The over-expression of POMC and GHITM suggests POMP peptide products may have undiscovered roles in early development and GHITM may contribute to mitochondrial remodeling. Under-detected on the 8-cell arrays at least tenfold were two key enzymes in steroid biosynthesis, DHCR24 and FDPS., Conclusions: The 8-cell human embryo may be secreting oxytocin, which could stimulate its own progress down the fallopian tube as well as play a role in early neural precursor development. The 8-cell embryo does not synthesize reproductive steroid hormones. As previously reported for growth factor families, the early embryo over-expresses more hormones than hormone receptors., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2024
- Full Text
- View/download PDF
3. Characterization of the long noncoding RNA transcriptome in human preimplantation embryo development.
- Author
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Zhang L, Sun H, and Chen X
- Subjects
- Pregnancy, Female, Humans, Embryonic Development genetics, Blastocyst metabolism, Morula metabolism, Gene Expression Profiling, Transcriptome genetics, RNA, Long Noncoding genetics
- Abstract
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., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2023
- Full Text
- View/download PDF
4. Early human embryos are naturally aneuploid—can that be corrected?
- Author
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Ann A. Kiessling and Amy S. Lee
- Subjects
0301 basic medicine ,Male ,animal structures ,medicine.medical_treatment ,Preimplantation genetic screening ,Aneuploidy ,Mitosis ,Review ,Fertilization in Vitro ,Biology ,Chromosome ,Andrology ,03 medical and health sciences ,0302 clinical medicine ,Human fertilization ,Meiosis ,Pregnancy ,In vitro fertilization ,Obstetrics and Gynaecology ,medicine ,Genetics ,Human embryo ,Humans ,Genetics(clinical) ,Genetics (clinical) ,Preimplantation Diagnosis ,030219 obstetrics & reproductive medicine ,In vitro fertilisation ,Aneuploid ,Pregnancy Outcome ,Obstetrics and Gynecology ,Embryo ,General Medicine ,medicine.disease ,Embryo Transfer ,Sperm ,Spermatozoa ,Embryo transfer ,Euploid ,030104 developmental biology ,Egg donor ,Reproductive Medicine ,embryonic structures ,Female ,Ploidy ,Developmental Biology - Abstract
Aneuploidy is common and may be a natural occurrence in early human embryos. Selecting against embryos containing aneuploid cells for embryo transfer has been reported to increase clinical pregnancies per transfer in some studies, but not others. Some aneuploidy is due to misallocation of chromosomes during meiosis, in either the egg or sperm, but most aneuploidy is due to misallocation of chromosomes during mitoses after fertilization. Big questions are as follows: Why does this happen? How much aneuploidy in a preimplantation embryo is compatible with normal fetal development? Is aneuploidy increased by in vitro culture, and/or could it be prevented or corrected in the IVF lab?
- Published
- 2016
5. Hypothesis: human trophectoderm biopsy downregulates the expression of the placental growth factor gene.
- Author
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Tocci A
- Subjects
- Female, Humans, Pregnancy, Ectoderm surgery, Gene Expression Regulation, Genetic Testing methods, Placenta surgery, Placenta Growth Factor antagonists & inhibitors, Surgical Procedures, Operative adverse effects, Trophoblasts chemistry
- Abstract
Preeclampsia (PE) and intrauterine growth retardation (IUGR) are the results of defective placentation associated with the downregulation of different genes in the human trophoblast including the Placental Growth Factor (PGF). TrophEctoderm (TE) biopsy is increasingly performed for Pre-implantation Genetic Testing of Aneuploidies and it involves the traumatical removal of an unpredictable number of mural TE cells from the human blastocyst. We observed strikingly similar obstetrical and neonatal complications in pregnancies where the placenta bears PGF downmodulation or a TE biopsy has been done. In both groups, the risk of PE, IUGR, congenital cardiac ventricular septal defects, caesarean section, sex ratio in favour of males and preterm birth is significantly increased compared to controls. Given the high degree of correlation, the observation may not be a casual one. We postulate herein that the TE biopsy may induce persistent dysregulation of different genes in the placenta including PGF. The mechanism proposed is the disruption of tight junctions caused by the TE biopsy., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2021
- Full Text
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6. The unknown human trophectoderm: implication for biopsy at the blastocyst stage.
- Author
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Tocci A
- Subjects
- Animals, Biopsy, Cell Differentiation genetics, Ectoderm metabolism, Embryo Implantation genetics, Female, Humans, Mice, Pregnancy, Trophoblasts cytology, Blastocyst cytology, Ectoderm growth & development, Preimplantation Diagnosis, Trophoblasts metabolism
- Abstract
Trophectoderm biopsy is increasingly performed for pre-implantation genetic testing of aneuploidies and considered a safe procedure on short-term clinical outcome, without strong assessment of long-term consequences. Poor biological information on human trophectoderm is available due to ethical restrictions. Therefore, most studies have been conducted in vitro (choriocarcinoma cell lines, embryonic and pluripotent stem cells) and on murine models that nevertheless poorly reflect the human counterpart. Polarization, compaction, and blastomere differentiation (e.g., the basis to ascertain trophectoderm origin) are poorly known in humans. In addition, the trophectoderm function is poorly known from a biological point of view, although a panoply of questionable and controversial microarray studies suggest that important genes overexpressed in trophectoderm are involved in pluripotency, metabolism, cell cycle, endocrine function, and implantation. The intercellular communication system between the trophectoderm cells and the inner cell mass, modulated by cell junctions and filopodia in the murine model, is obscure in humans. For the purpose of this paper, data mainly on primary cells from human and murine embryos has been reviewed. This review suggests that the trophectoderm origin and functions have been insufficiently ascertained in humans so far. Therefore, trophectoderm biopsy should be considered an experimental procedure to be undertaken only under approved rigorous experimental protocols in academic contexts.
- Published
- 2020
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7. Epigenetic remodeling of chromatin in human ART: addressing deficiencies in culture media.
- Author
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Ménézo Y and Elder K
- Subjects
- Amino Acids metabolism, Amino Acids pharmacology, Blastocyst drug effects, Congenital Abnormalities etiology, Congenital Abnormalities prevention & control, DNA Repair, Embryonic Development drug effects, Endocrine Disruptors toxicity, Female, Genomic Imprinting, Glucose metabolism, Glucose pharmacology, Humans, Infant, Newborn, Methionine administration & dosage, Methionine toxicity, Methylation, Methylenetetrahydrofolate Reductase (NADPH2) genetics, Oocytes drug effects, Oocytes metabolism, Oxidative Stress, Pregnancy, S-Adenosylmethionine metabolism, Blastocyst metabolism, Chromatin drug effects, Chromatin Assembly and Disassembly drug effects, Culture Media pharmacology, DNA Methylation, Embryo Culture Techniques, Reproductive Techniques, Assisted adverse effects
- Published
- 2020
- Full Text
- View/download PDF
8. Evidence that human blastomere cleavage is under unique cell cycle control
- Author
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Ann A. Kiessling, Dimitris Loutradis, R. Bletsa, Christina Mara, K. Kallianidis, and B. Desmarais
- Subjects
DNA Replication ,Male ,Pluripotent Stem Cells ,Blastomeres ,Cell cycle checkpoint ,Cell division ,Microarray ,CLOCK ,Cell Cycle Proteins ,Myc ,Proto-Oncogene Mas ,Obstetrics and Gynaecology ,Genetics ,Human embryo ,Humans ,Genetics(clinical) ,RNA, Messenger ,Cell Cycle Protein ,Induced pluripotent stem cell ,Retinoblastoma gene ,Human blastomere ,Genetics (clinical) ,UHRF2 ,Oligonucleotide Array Sequence Analysis ,biology ,Cell Cycle ,Totipotent ,Obstetrics and Gynecology ,General Medicine ,Blastomere ,Circadian oscillators ,Fibroblasts ,Cell cycle ,Circadian Rhythm ,Cell biology ,Wee1 ,Reproductive Medicine ,biology.protein ,Female ,Growth factor independent ,Cell Division ,Developmental Biology - Abstract
Purpose To understand the molecular pathways that control early human embryo development. Methods Improved methods of linear amplification of mRNAs and whole human genome microarray analyses were utilized to characterize gene expression in normal appearing 8-Cell human embryos, in comparison with published microarrays of human fibroblasts and pluripotent stem cells. Results Many genes involved in circadian rhythm and cell division were over-expressed in the 8-Cells. The cell cycle checkpoints, RB and WEE1, were silent on the 8-Cell arrays, whereas the recently described tumor suppressor, UHRF2, was up-regulated >10-fold, and the proto-oncogene, MYC, and the core element of circadian rhythm, CLOCK, were elevated up to >50-fold on the 8-Cell arrays. Conclusions The canonical G1 and G2 cell cycle checkpoints are not active in totipotent human blastomeres, perhaps replaced by UHRF2, MYC, and intracellular circadian pathways, which may play important roles in early human development. Electronic supplementary material The online version of this article (doi:10.1007/s10815-009-9306-x) contains supplementary material, which is available to authorized users.
- Published
- 2009
9. The role of microRNAs in human embryo implantation: a review.
- Author
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Paul ABM, Sadek ST, and Mahesan AM
- Subjects
- Endometrium growth & development, Female, Gene Expression Regulation, Developmental genetics, Humans, Pregnancy, Signal Transduction genetics, Embryo Implantation genetics, Endometrium metabolism, MicroRNAs genetics
- Abstract
MicroRNAs (miRNAs) are emerging as important in human embryo implantation, and we present here a review of the literature from a clinical perspective. Implantation involves complex interactions between the blastocyst and endometrium. miRNAs have been shown to be differentially expressed in implanted compared with non-implanted blastocysts and euploid compared with aneuploid blastocysts. Further, miRNAs are differentially expressed in proliferative compared with decidualized endometrium, and in receptive compared with pre-receptive endometrium. miRNAs are also differentially expressed in endometrium of women who failed implantation, and in endometrium of women with recurrent implantation failure. Due to the complexity of miRNA signaling, studies have suffered from inconsistency in reproducibility of results. However, miRNAs show potential as biomarkers in the pursuit of more reliable prediction of embryo implantation.
- Published
- 2019
- Full Text
- View/download PDF
10. Supercilious cell cycles in the human embryo
- Author
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David F. Albertini
- Subjects
Cell cycle checkpoint ,Cell division ,Somatic cell ,CLOCK ,Computational biology ,Cell fate determination ,Biology ,Chromosome Segregation ,Cyclins ,Genetics ,Humans ,Human embryo ,Mitosis ,Aurora kinase ,Genetics (clinical) ,Gene Library ,Genome, Human ,Cell Cycle ,Obstetrics and Gynecology ,Gene Expression Regulation, Developmental ,General Medicine ,Genomics ,Cell cycle ,Embryo, Mammalian ,Embryonic stem cell ,Embryo Biology ,Reproductive Medicine ,RB ,Cytokinesis ,Developmental Biology - Abstract
The 1980s and 1990s were witness to advances in our ability to comprehend the mysteries of the cell cycle; these advances continue to change and impact the face of contemporary biomedical research. Notwithstanding the immediate effects that this Nobel Prize-bearing topic (2004) has had on the understanding of cancer and the impetus it has provided for novel approaches to prevention and treatment, the cell cycle has assumed center stage in the field of human reproduction. This is true for three reasons: First is the issue of what distinguishes the meiotic cell cycle in gametes from that of their somatic cell counterparts. Even between the sexes, there is mounting evidence to suggest that while progressing through the rigors of spermatogenesis, a ruthless series of cell cycle checkpoints eliminates most all defective sperm. Second, the long acknowledged preponderance of aneuploidies exhibited by human oocytes, especially with advancing maternal age, has called into question the integrity of the controls responsible for eliminating chromosomally imbalanced ova. And finally, if suspicions exist as to the fidelity of chromosome balance in the female gametes, then what of the conceptus and its ability to monitor and dispense of blastomeres that harbor errors in chromosome segregation during the mitotic divisions of the preimplantation embryo? With over 30 years of ARTs experience and the evaluation of genetic integrity of human embryos under our belts, there is little left to the imagination—human embryos constitute an unusually striking example of cell cycles gone wrong! Why would this be? Here enters the paper by Kiessling and coworkers in this issue of JARG; studies that take a major step forward in elucidating the causes and consequences of genetic stability in human embryos. This report forecasts and illustrates the power of bioinformatics and, as in other disciplines of biomedical research, brings into focus one of the most confounding and disconcerting properties of human embryos: their propensity toward chromosome imbalance. Using microarrays of 8 cell human blastomeres, as well as array data from two human embryonic stem cell lines and human fibroblasts (both before and following iPS), the expression of transcripts relevant to cell cycle control was analyzed from a database of over 3,000 human genome mRNAs. What makes this work most provocative and insightful is that the ontology analyses were based upon genes known to play a central role in cell cycle progression from functional siRNA knockdown databases for two human cell lines: HeLa and U2OS. Based on the analysis of over 1,000 transcripts for each of these cell types, strong inferences were deduced relative to the levels of specific gene products detected in the human 8 cell blastomere arrays. In the broadest sense, 35 genes were identified as being overexpressed, including transcripts encoding for cell cycle “drivers,” while ten genes were identified as being underexpressed that notably included key checkpoint control gene products. Among the implications of these findings is the reinforcement of the notion that when it comes to cell cycle checkpoint surveillance, human embryos appear rather cavalier in their approach to achieving chromosome balance. What might speeding up the cell cycle with worn brakes accomplish? The authors argue that speed may be of the essence in order to drive development to the stage of compaction when reliance on growth factors to sustain embryogenesis assumes a central role coincident with the activation and deployment of the embryo’s genome. Kiessling and coworkers speculate further that drawing upon oscillators for gene expression to encourage timely gene duplication may come at a cost, as accelerating the cell cycle could lead to asynchrony between the processes of karyokinesis and cytokinesis in the absence of trident checkpoints that are normally deployed during the G1 and G2 phases of the cell cycle. So how will these findings influence the future of reproductive medicine? From a technical point of view, this work sets the stage for research into the precise molecular mechanisms that distinguish somatic cells, cancer cells, gametes and embryos from each other. Candidate genes are identified but there still exists the imperative to transform these leads into functional studies at the protein level. Two weaknesses of this approach are that the inferences drawn are solely based on mRNA expression data (not protein), and secondly, that neither of the cell lines used for siRNA functional studies are “normal” somatic cells. This means that the databases are suspect in their own right and may not provide an appropriate baseline for comparisons to human embryos and are likely incomplete given the nature of the cell cycle screens used to derive these databases. A recent paper in Nature (Neumann et al., 2010, “Phenotypic profiling of the human genome by time-lapse microscopy reveals cell division genes”, 464:721, doi:10.1038/nature08869) provides enhanced impetus for solving this problem. In what can only be described as a tour de force, an siRNA library designed to screen the approximately 21,000 protein-coding genes that grace the human genome was used to earmark cell division genes by time-lapse miscroscopy to assign specific phenotypes. The prize at hand? A data set derived from about 190,000 time-lapse movies that encoded 19 million HeLa cell divisions! This extraordinary feat, made possible through the international Mitocheck consortium, brings to the surface a public database from which studies like those of Kiessling et al. can now apply to their own work—at a level of functional and proteomic resolution that was not previously imaginable. The take-home message of the Neumann et al contribution inspires promise and awe. Not only is there now an exploitable library of gene products suspected to be involved in cell cycle control, with which we can interrogate the rich network databases in hand for human gametes and embryos, but this work uncovered many gene products of unexpected relevance that will also have to be explored. While it is difficult to know where we stand as a species in the spectrum of quality control for genome integrity, there is a lingering consensus within the field of ARTs that human embryos are at best woefully inept at handling the rigors of early cell divisions. Given the pace at which ARTs have moved from the bench to bedside over the past 30 years, perhaps it is time to slow down—instead of following the example of the human embryo’s approach to the cell cycle (“faster is better”). Maybe we should step back and take the time to carefully monitor our progress and status, like a good cell cycle!
- Published
- 2010
11. Early human embryos are naturally aneuploid-can that be corrected?
- Author
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Lee A and Kiessling AA
- Subjects
- Embryo Transfer methods, Female, Humans, Male, Pregnancy, Pregnancy Outcome, Preimplantation Diagnosis, Spermatozoa growth & development, Spermatozoa pathology, Aneuploidy, Fertilization in Vitro, Meiosis genetics, Mitosis genetics
- Abstract
Aneuploidy is common and may be a natural occurrence in early human embryos. Selecting against embryos containing aneuploid cells for embryo transfer has been reported to increase clinical pregnancies per transfer in some studies, but not others. Some aneuploidy is due to misallocation of chromosomes during meiosis, in either the egg or sperm, but most aneuploidy is due to misallocation of chromosomes during mitoses after fertilization. Big questions are as follows: Why does this happen? How much aneuploidy in a preimplantation embryo is compatible with normal fetal development? Is aneuploidy increased by in vitro culture, and/or could it be prevented or corrected in the IVF lab?
- Published
- 2017
- Full Text
- View/download PDF
12. Comparison of 2, 5, and 20 % O2 on the development of post-thaw human embryos.
- Author
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Yang Y, Xu Y, Ding C, Khoudja RY, Lin M, Awonuga AO, Dai J, Puscheck EE, Rappolee DA, and Zhou C
- Subjects
- Blastocyst drug effects, Connexin 43 genetics, Cryopreservation, DNA-Binding Proteins genetics, Female, Glucose Transporter Type 1 genetics, Glucosephosphate Dehydrogenase genetics, Humans, Infertility, Female, Infertility, Male, Intracellular Signaling Peptides and Proteins genetics, Male, Nuclear Proteins genetics, RNA, Messenger biosynthesis, Superoxide Dismutase genetics, bcl-2-Associated X Protein genetics, Apoptosis drug effects, Blastocyst cytology, Embryo Culture Techniques methods, Embryo Transfer methods, Embryonic Development drug effects, Oxygen pharmacology
- Abstract
Purpose: The objective of this study is to investigate the effect of 2, 5, and 20 % O2 on post-thaw day 3 human embryo culture until blastocyst stage., Methods: One hundred fifty-five day 3 human embryos were used. One hundred twenty out of 155 embryos were recovered after thawing. Surviving embryos were distributed into 2, 5, or 20 % O2 groups and cultured for 2.5 days. At the end of culture, blastocyst formation was assessed, and then, embryos were collected for RT-qPCR or immunofluorescence analysis., Results: Using visible blastocoel to define blastocyst formation, 58.7 % (27/46) of surviving day 3 embryos formed blastocyst at 2 % O2, 63.6 % (28/44) at 5 % O2, and 66.7 % (20/30) at 20 % O2. The difference in blastocyst formation rates was not significant. Average blastocyst cell number was 119.44 ± 11.64 at 2 % O2, 142.55 ± 22.47 at 5 % O2, and 97.29 ± 14.87 at 20 % O2. Average apoptotic rate was 4.7 % ± 0.4 % for blastocyst formed at 2 % O2, 3.5 % ± 0.7 % at 5 % O2, and 5.8 % ± 1.1 % at 20 % O2. Apoptosis rate was significantly lower for blastocysts formed at 5 % O2 (p < 0.05). Compared with gene expression levels at 5 % O2, which were arbitrarily set as "1," 20 % O2 is associated with significantly higher expression of BAX (2.14 ± 0.47), G6PD (2.92 ± 1.06), MnSOD (2.87 ± 0.88), and HSP70.1 (8.68 ± 4.19). For all genes tested, no significant differences were found between 2 and 5 % O2., Conclusion: The result suggests that development of cryopreserved human embryos from day 3 to blastocyst stage benefits from culture at 5 % O2.
- Published
- 2016
- Full Text
- View/download PDF
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