scholarly journals Biological and Clinical Significance of Mosaicism in Human Preimplantation Embryos

2021 ◽  
Vol 9 (2) ◽  
pp. 18
Author(s):  
Ioanna Bouba ◽  
Elissavet Hatzi ◽  
Paris Ladias ◽  
Prodromos Sakaloglou ◽  
Charilaos Kostoulas ◽  
...  

Applications and indications of assisted reproduction technology are expanding, but every new approach is under scrutiny and thorough consideration. Recently, groups of assisted reproduction experts have presented data that support the clinical use of mosaic preimplantation embryos at the blastocyst stage, previously excluded from transfer. In the light of published contemporary studies, with or without clinical outcomes, there is growing evidence that mosaic embryos have the capacity for further in utero development and live birth. Our in-depth discussion will enable readers to better comprehend current developments. This expansion into the spectrum of ART practices requires further evidence and further theoretical documentation, basic research, and ethical support. Therefore, if strict criteria for selecting competent mosaic preimplantation embryos for further transfer, implantation, fetal growth, and healthy birth are applied, fewer embryos will be excluded, and more live births will be achieved. Our review aims to discuss the recent literature on the transfer of mosaic preimplantation embryos. It also highlights controversies as far as the clinical utilization of preimplantation embryos concerns. Finally, it provides the appropriate background to elucidate and highlight cellular and genetic aspects of this novel direction.

Zygote ◽  
1994 ◽  
Vol 2 (4) ◽  
pp. 281-287 ◽  
Author(s):  
Asangla Ao ◽  
Robert P. Erickson ◽  
Robert M.L. Winston ◽  
Alan H Handysude

SummaryGlobal activation of the embryonic genome occurs at the 4– to 8–cell stage in human embryos and is marked by continuation of early cleavage divisions in the presence of transcriptional inhibitors. Here we demonstrate, using recerse transcripase–polymerase chin reaction (Rt–PCR), the presence of transcripts for wo paternal Y chromosomal genes, ZFY and SRY in human preimplantation embryos. ZFY transcripts were detected as early as the pronucleate stage, 20–24 h post-insemination In vitro and at intermediate stages up to the blastocyst stage. SRY Transcripts were also detected at 2–cell to blastocyos observed in many mammalian species focuses attention on the role of events in six determination prior to gonad differentiation.


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Nilay Kuşcu ◽  
Mariano Bizzarri ◽  
Arturo Bevilacqua

Myo-inositol (myo-Ins) has a physiological role in mammalian gametogenesis and embryonic development and a positive clinical impact on human medically assisted reproduction. We have previously shown that mouse embryo exposure to myo-Ins through preimplantation developmentin vitroincreases proliferation activity and blastocyst production, representing an improvement in culture conditions. We have herein investigated biochemical mechanisms elicited by myo-Ins in preimplantation embryos and evaluated myo-Ins effects on postimplantation/postnatal development. To this end naturally fertilized embryos were culturedin vitroto blastocyst in the presence or absence of myo-Ins and analyzed for activation of the PKB/Akt pathway, known to modulate proliferation/survival cellular processes. In parallel, blastocyst-stage embryos were transferred into pseudopregnant females and allowed to develop to term and until weaning. Results obtained provide evidence that myo-Ins induces cellular pathways involving Akt and show that (a) exposure of preimplantation embryos to myo-Ins increases the number of blastocysts available for uterine transfer and of delivered animals and (b) the developmental patterns of mice obtained from embryos cultured in the presence or absence of myo-Ins, up to three weeks of age, overlap. These data further identify myo-Ins as a possibly important supplement for human preimplantation embryo culture in assisted reproduction technology.


Zygote ◽  
2019 ◽  
Vol 27 (02) ◽  
pp. 97-100
Author(s):  
P. Tulay ◽  
H. Arslan ◽  
A. Buran ◽  
Y. Koprulu

SummaryDifferent parameters affect the success of assisted reproduction technology (ART) treatments. One of the advantages of using intracytoplasmic sperm injection (ICSI) is that it also enables the assessment of the oocyte morphology. To date there has not been a clear conclusion on aberrant oocyte morphology and its consequences on the success of ART treatments. Therefore, in this study, we aimed to investigate the fertilization, embryo development and pregnancy rates in patients who have oocytes with granular cytoplasm. Additionally, we investigated if there were more aneuploid embryos obtained from abnormal cytoplasmic morphology. In total, 5704 oocytes were collected and, of these, 4036 were metaphase II (MII) oocytes. The morphology of these oocytes was assessed following denudation and 970 oocytes were observed to have granular cytoplasm. There was no difference in the fertilization rates between the oocytes with normal cytoplasm (89%) and oocytes with granular cytoplasm (72%). Cleavage of embryos and the number of embryos that reached the blastocyst stage were also similar in these two groups. The aneuploidy rates between the two groups were also similar. However, clinical pregnancies were significantly lower in embryos obtained from oocytes with granular cytoplasm (37.5% vs 70%, P<0.05). Therefore, the morphology of the oocyte is as important as morphology of the sperm. Even though normal fertilization and cleavage were achieved from oocytes with granular cytoplasm, their implantation potential was significantly compromised.


2020 ◽  
Vol 35 (8) ◽  
pp. 1797-1807 ◽  
Author(s):  
Robbert P Berkhout ◽  
Remco Keijser ◽  
Sjoerd Repping ◽  
Cornelis B Lambalk ◽  
Gijs B Afink ◽  
...  

Abstract STUDY QUESTION How do high-quality human preimplantation embryos influence the endometrium to promote their own implantation? SUMMARY ANSWER High-quality human preimplantation embryos secrete a specific microRNA (miRNA), hsa-miR-320a, which promotes migration of human endometrial stromal cells (hESCs). WHAT IS KNOWN ALREADY We have previously shown that high-quality human preimplantation embryos excrete unknown factors that influence migration of hESCs. STUDY DESIGN, SIZE, DURATION Embryo excreted miRNAs, specifically those excreted by high-quality embryos, were identified and their effect on hESCs was determined by measuring the migration capacity and gene expression patterns of primary isolated hESCs. PARTICIPANTS/MATERIALS, SETTING, METHODS Embryo conditioned medium (ECM) from routine ICSI procedures was used to identify embryo excreted miRNAs. miRNome analyses were performed on ECM from individually cultured embryos with high morphological quality, with low morphological quality or empty control medium. MiRNA mimics and inhibitors were then used to further study the effect of miRNAs of interest on migration and gene expression of hESCs. Migration assays were performed using hESCs that were obtained from endometrial biopsies performed on hysterectomy specimens from women that received surgery for spotting due to a niche in a cesarean section scar. MAIN RESULTS AND THE ROLE OF CHANCE By using miRNA mimics and inhibitors, we showed that hsa-miR-320a alone can stimulate migration of decidualized hESCs, accurately resembling the response typically triggered only by high-quality embryos. Transcriptome analysis further demonstrated that this effect is very likely mediated via altered expression of genes involved in cell adhesion and cytoskeleton organization. LIMITATIONS, REASONS FOR CAUTION The effect of hsa-miR-320a on hESCs was measured in vitro. Further studies on the in vivo effect of hsa-miR-320a are warranted. WIDER IMPLICATIONS OF THE FINDINGS Implantation failure is one of the major success limiting factors in human reproduction. By secreting hsa-miR-320a, high-quality human preimplantation embryos directly influence hESCs, most likely to prime the endometrium at the implantation site for successful implantation. Together, our results indicate that hsa-miR-320a may be a promising target to further increase success rates in assisted reproduction. STUDY FUNDING/COMPETING INTEREST(S) The study was funded by the Amsterdam University Medical Centers and the Amsterdam Reproduction & Development Research Institute. R.P.B., G.H. and S.M. have a patent on the use of hsa-miR-320a in assisted reproduction treatments pending. TRIAL REGISTRATION NUMBER N/A.


2002 ◽  
Vol 87 (6) ◽  
pp. 2629-2634 ◽  
Author(s):  
Hongbo Wang ◽  
Yan Wen ◽  
Stephen Mooney ◽  
Barry Behr ◽  
Mary Lake Polan

Phospholipase A2 (PLA2) and cyclooxygenase (COX) are two key enzymes in PG synthesis; the latter has two forms, COX-1 and COX-2. mRNA was extracted from single preimplantation embryos and examined for PLA2, COX-1, and COX-2 gene expression by RT-PCR to investigate whether PLA2 and COX genes are expressed in human preimplantation conceptuses from zygote to blastocyst stage and to compare COX-1 and COX-2 gene expression within the same stage of embryonic development. Expression of PLA2, COX-1, and COX-2 was detected in 48, 37, and 45%, respectively, of total embryos examined. COX-1 was expressed in approximately 66% of early human preimplantation embryos from zygote to two-cell stage, whereas COX-2 was expressed in about 58% of later stage embryos from eight-cell to blastocyst stage (P < 0.05). Furthermore, COX-2 mRNA and protein were localized to trophectoderm in blastocyst stage embryos. In conclusion, PLA2, COX-1, and COX-2 are expressed during early human embryonic development and may contribute to the production of PGs such as PGE2 in human embryogenesis. COX-1 and COX-2 are differentially expressed, with COX-2 being primarily expressed by trophectoderm in late-stage human preimplantation embryos, which may promote embryonic differentiation and implantation.


2019 ◽  
pp. 20-22
Author(s):  
T.I. KUZMINA ◽  
I.V. CHISTYAKOVA

Создание эффективной унифицированной системы дозревания донорских ооцитов обеспечит повышение результативности инновационных клеточных репродуктивных технологий. В исследовании проведен сравнительный мониторинг показателеймейотического созревания ооцитов коров, созревших в различных системах, дополненных структурными компонентами фолликулов (СКФ стенки фолликулов, клетки гранулезы, белки) и фолликулярной жидкостью,а также потенций к развитию из них доимплантационных эмбрионов. Анализу подверглись ооциты, прокультивированные в следующих системах:среда ТС199 с добавлением 10 фетальной бычьей сыворотки (ФБС), 50 мкг/мл эстрадиола, 10 мкг/мл лютеинизирующего гормона (ЛГ), 10 мкг/мл фолликулостимулирующего гормона (ФСГ) среда ТС199 с 10 эстральной сывороткой коров среда ТС199 с 50 жидкости из фолликулов диаметром 9 мм среда ТС199 с добавлением белков фолликулярной жидкости молекулярной массой 65 кДасреда ТС199 с 10 ФБС и 1106 клеток гранулезы среда ТС199 с 10 ФБС и тканью фолликула. В культуральные среды ко всем исследованным группам ооцитов добавляли антибиотики. Использование CКФ обеспечило значительное снижение доли ооцитов с дегенерированным хроматином, что способствовало увеличению уровня доимпланационных эмбрионов на стадии бластоцисты. Так, доля бластоцист, развившихся из ооцитов, созревших в среде со стенками фолликулов,составила43,5. В этой же группе выявлен минимальный уровень дегенерированных зародышей (6,45). Полученные данные предлагается использовать при моделировании систем дозревания ооцитов коров с целью повышения качества яйцеклеток.The creation of an effective unified maturation system of donor oocytes provides an increase in the efficiency of innovative cellular reproductive technologies. The comparative analysis of the meiotic maturation indicators of bovine oocytes, which were matured in different cultural systems modified by follicular structural components (FSC follicular walls, granulosa cells, proteins) and follicular fluid, as well as the potential for preimplantation embryonic development were evaluated in this study. Oocytes matured in following cultural systems: medium TC199 supplemented with 10 fetal bovine serum and 50 g/ml of estradiol, 10 g/ml of luteinizing hormone (LH), 10 g/ml of folliclestimulating hormone (FSH) medium TC199 with 10 estrous cow serum medium TC199 with 50 liquid from follicles with a diameter of 9 mm medium TC199 supplemented with the follicular fluid proteins with molecular weight 65 kDa medium TC199 with 10 fetal bovine serum and 1106 granulosa cells medium TC199 with the addition of 10 fetal bovine serum and follicle tissues were analyzed. Antibiotics were added to cultural media of all experimental groups of oocytes. The usage of FSC ensured the decrease in the proportion of oocytes with degenerated chromatin, which contribute the rise of the level of preimplantation embryos at the blastocyst stage. Thus, the proportion of blastocysts developed from oocytes matured in medium supplemented with follicular walls was 43.5. In the same experimental group, the number of degenerated embryos was 6.45. The obtained data are supposed to be used for modeling the cultural systems of cow oocytes in order to improve the egg quality.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Laura Santini ◽  
Florian Halbritter ◽  
Fabian Titz-Teixeira ◽  
Toru Suzuki ◽  
Maki Asami ◽  
...  

AbstractIn mammalian genomes, differentially methylated regions (DMRs) and histone marks including trimethylation of histone 3 lysine 27 (H3K27me3) at imprinted genes are asymmetrically inherited to control parentally-biased gene expression. However, neither parent-of-origin-specific transcription nor imprints have been comprehensively mapped at the blastocyst stage of preimplantation development. Here, we address this by integrating transcriptomic and epigenomic approaches in mouse preimplantation embryos. We find that seventy-one genes exhibit previously unreported parent-of-origin-specific expression in blastocysts (nBiX: novel blastocyst-imprinted expressed). Uniparental expression of nBiX genes disappears soon after implantation. Micro-whole-genome bisulfite sequencing (µWGBS) of individual uniparental blastocysts detects 859 DMRs. We further find that 16% of nBiX genes are associated with a DMR, whereas most are associated with parentally-biased H3K27me3, suggesting a role for Polycomb-mediated imprinting in blastocysts. nBiX genes are clustered: five clusters contained at least one published imprinted gene, and five clusters exclusively contained nBiX genes. These data suggest that early development undergoes a complex program of stage-specific imprinting involving different tiers of regulation.


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