Human oocyte developmental potential is predicted by mechanical properties within hours after fertilization.
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ABSTRACT:
SUBMITTER: Yanez LZ
PROVIDER: S-EPMC4770082 | biostudies-literature | 2016 Feb
REPOSITORIES: biostudies-literature
Publications
Human oocyte developmental potential is predicted by mechanical properties within hours after fertilization.
Yanez Livia Z LZ Han Jinnuo J Behr Barry B BB Pera Renee A Reijo RAR Camarillo David B DB
Nature communications 20160224
The causes of embryonic arrest during pre-implantation development are poorly understood. Attempts to correlate patterns of oocyte gene expression with successful embryo development have been hampered by the lack of reliable and nondestructive predictors of viability at such an early stage. Here we report that zygote viscoelastic properties can predict blastocyst formation in humans and mice within hours after fertilization, with >90% precision, 95% specificity and 75% sensitivity. We demonstrat ...[more]
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Project description:Study questionIs the abundance of certain biochemical compounds in human cumulus cells (CCs) related to oocyte quality?Summary answerMalonate, 5-oxyproline, and erythronate were positively associated with pregnancy potential.What is known alreadyCCs are removed and discarded prior to ICSI, thereby constituting an interesting biological material on which to perform molecular analysis aimed to predict oocyte developmental competence. Mitochondrial DNA content and transcriptional analyses in CC have been shown to provide a poor predictive value of oocyte competence, but the untargeted analysis of biochemical compounds (metabolomics) has been unexplored.Study design, size, durationCCs were obtained from three groups of cumulus-oocyte complexes (COCs) of known developmental potential: oocytes not developing to blastocyst following ICSI (Bl-); oocytes developing to blastocyst but failing to establish pregnancy following embryo transfer (P-); and oocytes developing to blastocyst able to establish a pregnancy (P+). Metabolomics analyses were performed on 12 samples per group, each sample comprising the CC recovered from a single COC.Participants/materials, setting, methodsHuman CC samples were obtained from IVF treatments. Only unfrozen oocytes and embryos not submitted to preimplantation genetic testing were included in the analysis. Metabolomics analysis was performed by ultra-high performance liquid chromatography-tandem mass spectroscopy.Main results and the role of chanceThe analysis identified 98 compounds, five of which were differentially abundant (P < 0.05) between groups: asparagine, proline, and malonate were less abundant in P- compared to Bl-, malonate and 5-oxoproline were less abundant in P- group compared to P+, and erythronate was less abundant in Bl- group compared to P+. No significant association between the abundance of the compounds identified and donor age or BMI was noted.Limitations, reasons for cautionData dispersion and the lack of coherence between developmental groups preclude the direct use of metabolic markers in clinical practice, where the uterine environment plays a major role in pregnancy outcome. The abundance of other compounds not detected by the analysis may be associated with oocyte competence. As donors were lean (only two with BMI > 30 kg/m2) and young (<34 years old), a possible effect of obesity or advanced age on the CC metabolome could not be determined.Wider implications of the findingsThe abundance of malonate, 5-oxyproline, and erythronate in CC was significantly higher in COCs ultimately establishing pregnancy, providing clues on the pathways required for oocyte competence. The untargeted analysis uncovered the presence of compounds that were not expected in CC, such as β-citrylglutamate and the neurotransmitter N-acetyl-aspartyl-glutamate, which may play roles in chromatin remodeling and signaling, respectively.Study funding/competing interest(s)Research was supported by the Industrial Doctorate Project IND2017/BIO-7748 funded by Madrid Region Government. The authors declare no competing interest.Trial registration numberN/A.
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Project description:PurposeThe aim of this study was to non-invasively validate the developmental potential of human single pronucleated (1PN) zygotes derived from conventional in vitro fertilization (c-IVF) at the zygote stage.MethodsFifty 1PN zygotes derived from 45 patients undergoing c-IVF were used. Immunohistochemistry and fluorescence live cell imaging were used to confirm normal chromosome segregation during the first mitosis. The usefulness of measuring pronuclear diameter was assessed on the basis of the presence or absence of a proper first cleavage and validated by subsequent development.ResultsAlthough approximately 80% (15/19) of 1PN zygotes contained a diploid genome, immunohistochemistry revealed an unequal distribution of paternal and maternal genomes at the first mitosis. Fluorescence live imaging revealed that 73% (8/11) of 1PN zygotes formed a functional mitotic spindle at the first mitosis resulting from diploid genomes, with 25% (2/8) of these forming a tripolar spindle. 1PN zygotes in which the pronucleus disappeared and that subsequently underwent cleavage had a pronuclear diameter ≥ 32.2 μm. The selection of 1PN zygotes based on pronuclear diameter resulted in zygotes that all formed mitotic spindles with poles during cleavage. Furthermore, 63% (5/8) of these zygotes reached the blastocyst stage.ConclusionsThis study demonstrates the usefulness of a non-invasive assessment of 1PN zygotes derived from c-IVF as an indicator of developmental potential. Furthermore, diploid 1PN zygotes do not always exhibit normal chromosome segregation at the first mitosis. A pronuclear diameter ≥ 32.2 μm just before PN breakdown might be a useful criterion to assess 1PN zygotes that are capable of further development.
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Project description:Cumulus cells provide an interesting biological material to perform analyses to understand the molecular clues determining oocyte competence. The objective of this study was to analyze the transcriptional differences between cumulus cells from oocytes exhibiting different developmental potentials following individual in vitro embryo production by RNA-seq. Cumulus cells were allocated into three groups according to the developmental potential of the oocyte following fertilization: (1) oocytes developing to blastocysts (Bl+), (2) oocytes cleaving but arresting development before the blastocyst stage (Bl-), and (3) oocytes not cleaving (Cl-). RNAseq was performed on 4 (Cl-) or 5 samples (Bl+ and Bl-) of cumulus cells pooled from 10 cumulus-oocyte complexes per group. A total of 49, 50, and 18 differentially expressed genes (DEGs) were detected in the comparisons Bl+ versus Bl-, Bl+ versus Cl- and Bl- versus Cl-, respectively, showing a fold change greater than 1.5 at an adjusted p value <0.05. Focussing on DEGs in cumulus cells from Bl+ group, 10 DEGs were common to both comparisons (10/49 from Bl+ vs. Bl-, 10/50 from Bl+ vs. Cl-). These DEGs correspond to 6 upregulated genes (HBE1, ITGA1, PAPPA, AKAP12, ITGA5, and SLC1A4), and 4 downregulated genes (GSTA1, PSMB8, FMOD, and SFRP4) in Bl+ compared to the other groups, from which 7 were validated by quantitative PCR (HBE1, ITGA1, PAPPA, AKAP12, ITGA5, PSMB8 and SFRP4). These genes are involved in critical biological functions such as integrin-mediated cell adhesion, oxygen availability, IGF and Wnt signaling or PKA pathway, highlighting specific biological processes altered in incompetent in vitro maturation oocytes.
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Project description:BackgroundFemale infertility is a worldwide concern and the etiology of infertility has not been thoroughly demonstrated. Although the mouse is a good model system to perform functional studies, the differences between mouse and human also need to be considered. The objective of this study is to elucidate the different molecular mechanisms underlying oocyte maturation and fertilization between human and mouse.ResultsA comparative transcriptome analysis was performed to identify the differentially expressed genes and associated biological processes between human and mouse oocytes. In total, 8513 common genes, as well as 15,165 and 6126 uniquely expressed genes were detected in human and mouse MII oocytes, respectively. Additionally, the ratios of non-homologous genes in human and mouse MII oocytes were 37 and 8%, respectively. Functional categorization analysis of the human MII non-homologous genes revealed that cAMP-mediated signaling, sister chromatid cohesin, and cell recognition were the major enriched biological processes. Interestingly, we couldn't detect any GO categories in mouse non-homologous genes.ConclusionsThis study demonstrates that human and mouse oocytes exhibit significant differences in gene expression profiles during oocyte maturation, which probably deciphers the differential molecular responses to oocyte maturation and fertilization. The significant differences between human and mouse oocytes limit the generalizations from mouse to human oocyte maturation. Knowledge about the limitations of animal models is crucial when exploring a complex process such as human oocyte maturation and fertilization.
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