Mouse embryo culture as quality control for human in vitro fertilization: the one-cell versus the two-cell model

Davidson, Ady; Vermesh, Michael; Løbo, Rogerio A.; Paulson, Richard J.

doi:10.1016/s0015-0282(16)59783-0

Cited by 89 publications

(28 citation statements)

References 14 publications

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“…Different superscripts indicate a significant (P < 0.05) difference between treatments. If no superscripts are present, there were no significant differences (P>0.1) between treatments environment than MEAs using two-cell embryos [7,13,15]. We hypothesized that IVM would be useful for MEAs because of their reduced developmental potential compared to one-cell embryos, [25,38,39].…”

Section: Discussionmentioning

confidence: 99%

“…One-cell embryos have not developed all of the necessary mechanisms to maintain intracellular homeostasis [9] and have not yet activated the embryonic genome [10,11], so they are very sensitive to the culture environment [4,12]. As a result, several studies have demonstrated that MEAs using one-cell embryos are more sensitive than MEAs utilizing two-cell embryos [7,13]. Alternatively, the gas atmosphere, culture volume, embryo density, and concentration of protein during the MEA can be manipulated.…”

Section: Introductionmentioning

confidence: 99%

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Building a better mouse embryo assay: effects of mouse strain and in vitro maturation on sensitivity to contaminants of the culture environment

Herrick

Paik

Strauss

et al. 2015

J Assist Reprod Genet

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Purpose The aim of this study is to compare the sensitivity of the standard one-cell mouse embryo assay (MEA) to that using in vitro-matured oocytes from hybrid and outbred mice. Methods The study was done by culturing embryos in the presence or absence of two concentrations (0.0005 or 0.001 %v/v) of Triton X-100 (TX100). Embryonic development, blastocyst cell numbers (total and allocation to the trophectoderm [TE] and inner cell mass [ICM]), and blastocyst gene expression were evaluated. Results Neither concentration of TX100 affected (P>0.05) cleavage, blastocyst development, or hatching in one-cell embryos from BDF1 mice. However, all cell number endpoints were reduced (P<0.05) by the high concentration of TX100 and the number of ICM cells was reduced (P<0.05) by the low concentration of TX100. Inhibitory (P<0.05) effects of the high concentration of TX100 were observed in in vitro maturation (IVM) embryos from BDF1, CF1, and SW, but not ICR, mice. Cell number and allocation were negatively affected by the high concentration of TX100 in CF1 and SW embryos, but not in BDF1 or ICR embryos. The only developmental endpoints affected by the low concentration of TX100 were cleavage of BDF1 oocytes, blastocyst development of SW embryos, and cell numbers (total and inner cell mass (ICM)) of SW blastocysts. Conclusions The sensitivity of the MEA to TX100 is improved by using embryos from in vitro-matured oocytes, using oocytes from some outbred (SW or CF1, not ICR) strains of mice, and evaluating blastocyst cell number and allocation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Building a better mouse embryo assay: effects of mouse strain and in vitro maturation on sensitivity to contaminants of the culture environment

Herrick

Paik

Strauss

et al. 2015

J Assist Reprod Genet

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“…Although mouse embryo assays screen for toxins by simulating human embryo culture conditions the lack of standardization leads to variability in results [6]. Culture techniques have been employed to improve the sensitivity of the MEA, such as culturing fresh vs frozen embryos, using 1-cell vs 2-cell embryos or removing the zona pellucida prior to culture [7][8][9]. The 1-cell MEA, when compared to the 2-cell MEA, is ten times more sensitive for the toxin, Cidex, a common surgical sterilizing solution [7,10].…”

Section: Introductionmentioning

confidence: 99%

Peroxides in mineral oil used for in vitro fertilization: defining limits of standard quality control assays

Hughes¹,

Morbeck

Hudson³

et al. 2010

J Assist Reprod Genet

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Purpose To determine the relative sensitivities of the 1 and 2-cell mouse embryo assays (MEA) and the human sperm motility assay (HSMA) for peroxides in mineral oil. The effect of peroxide on blastocyst cell number and apoptosis was also studied. Methods One and two-cell MEA and HSMA were performed using mineral oil containing cumene hydroperoxide (CH).Results The 1-cell MEA was twice as sensitive as the 2-cell MEA and 20-times more sensitive than the HSMA for CH in mineral oil. The sensitivity of the 1-cell MEA doubled when embryos were cultured individually versus group culture. CH decreased blastocyst cell number in a dose dependent manner.Conclusions Individually cultured 1-cell embryos had the highest sensitivity for peroxides in mineral oil. Current quality control assays, including group cultured murine embryos and human sperm motility, have limited sensitivity for peroxides in mineral oil and may not detect levels of peroxides that cause sub-lethal cellular damage.

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“…Though a direct comparison of bioassays to human embryos is unlikely, validation of bioassay sensitivity using a robust scientific method is critical to assure that manufacturers and IVF laboratories are using the most sensitive and appropriate assays available. Most studies report toxicity of individual laboratory items without an identification of the toxin (Naz et al, 1986;Fleming et al, 1987;Claassens et al, 2000); however, reports with concentrations of known or suspected toxins have consistently demonstrated that the 1-cell MEA is superior to the 2-cell MEA or the sperm survival assay (Davidson et al, 1988;Scott et al, 1993;Hughes et al, 2010;Morbeck et al, 2010). Even though the 1-cell MEA is the industry standard, mineral oil that passed manufacturer QC illustrates that the assay, with BR as an end-point, can fail to detect clinically relevant toxins.…”

Section: Discussionmentioning

confidence: 99%

“…Bioassays employed by manufacturers and individual laboratories include the 1-cell and 2-cell mouse embryo assay (MEA) and the human sperm motility assay (HSMA). While the 1-cell MEA is more sensitive than the 2-cell MEA (Davidson et al, 1988;Scott et al, 1993;Hughes et al, 2010;Morbeck et al, 2010) or HSMA (Hughes et al, 2010), it is unclear if the sensitivity of these assays is sufficient to detect toxins relevant to the human IVF laboratory. Strain-to-strain variation provides evidence that the current standard for QC testing, which uses the 1-cell F1 hybrid mouse MEA, may not be sensitive enough to detect contaminants that affect human gametes and embryos (Khan et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Advances in quality control: mouse embryo morphokinetics are sensitive markers of in vitro stress

Wolff

Fredrickson

Walker

et al. 2012

Fertility and Sterility

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what is known already: Current quality control testing methodology is sensitive but further improvements are needed to assure optimal culture conditions. MKs of embryo development may detect small variations in culture conditions. study design: Cross sectional-control versus treatment. Mouse embryo development kinetics of 466 embryos were analyzed according to exposure to various concentrations of toxins and toxic mineral oil. materials, setting, methods: Cryopreserved 1-cell embryos from F1 hybrid mice were cultured with cumene hydroperoxide (CH) (0, 2, 4, 6 and 8 mM) and Triton X-100 (TX-100; 0, 0.0008, 0.0012, 0.0016 and 0.002%). Using the Embryoscope, time-lapse images were obtained every 20 min for 120 h in seven focal planes. End-points were timing and pattern of cell division and embryo development. The blastocyst rate (BR) was defined as the percentage of embryos that developed to the expanded blastocyst stage within 96 h. main results and the role of chance: BR was not affected for embryos cultured in the three lowest concentrations of CH and the four lowest concentrations of TX-100. In contrast, a unique MK model detected all concentrations tested (P , 0.05). The MK model identified toxicity in two lots of toxic mineral oil that did not affect BR (P , 0.05).limitations, reasons for caution: A limited number of toxins were used so that the results may not apply to all potential embryo toxins. A larger sample size may also demonstrate other statistically significant developmental kinetic parameters.wider implications of the findings: MKs in mouse embryos are a sensitive and efficient method for quality control testing of in vitro culture conditions. BR, the end-point of traditional quality control assays, did not detect sublethal concentrations of toxins in the culture milieu in our study. This study demonstrates that temporal variation at key developmental stages reflects the quality of the culture environment. An MEA that incorporates MK will provide enhanced sensitivity and faster turn-around times.

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Mouse embryo culture as quality control for human in vitro fertilization: the one-cell versus the two-cell model

Cited by 89 publications

References 14 publications

Building a better mouse embryo assay: effects of mouse strain and in vitro maturation on sensitivity to contaminants of the culture environment

Building a better mouse embryo assay: effects of mouse strain and in vitro maturation on sensitivity to contaminants of the culture environment

Peroxides in mineral oil used for in vitro fertilization: defining limits of standard quality control assays

Advances in quality control: mouse embryo morphokinetics are sensitive markers of in vitro stress

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