Mitochondrial DNA content in embryo culture medium is significantly associated with human embryo fragmentation

Stigliani, Sara; Anserini, Paola; Venturini, P. L.; Scaruffi, Paola

doi:10.1093/humrep/det314

Cited by 128 publications

(127 citation statements)

References 51 publications

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“…The replication of mitochondrial DNA is under dynamic regulation during pre-implantation development (Cagnone et al 2016) and stress responses could trigger the release of this DNA into the culture medium (due to cell death or clearance of damaged mitochondria). Recent studies have shown that an increased copy number of the mtDNA genome in embryonic cells and in spent media is a sign of a metabolic response to developmental stress (Stigliani et al 2013(Stigliani et al , 2014.…”

Section: Mitochondrial Signallingmentioning

confidence: 99%

The embryonic stress response to in vitro culture: insight from genomic analysis

Cagnone

Sirard

2016

Reproduction

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Recent genomic studies have shed light on the impact of in vitro culture (IVC) on embryonic homeostasis and the differential gene expression profiles associated with lower developmental competence. Consistently, the embryonic stress responses to IVC conditions correlate with transcriptomic changes in pathways related to energetic metabolism, extracellular matrix remodelling and inflammatory signalling. These changes appear to result from a developmental adaptation that enhances a Warburg-like effect known to occur naturally during blastulation. First discovered in cancer cells, the Warburg effect (increased glycolysis under aerobic conditions) is thought to result from mitochondrial dysfunction. In the case of IVC embryos, culture conditions may interfere with mitochondrial maturation and oxidative phosphorylation, forcing cells to rely on glycolysis in order to maintain energetic homeostasis. While beneficial in the short term, such adaptations may lead to epigenetic changes with potential long-term effects on implantation, foetal growth and post-natal health. We conclude that lessening the detrimental effects of IVC on mitochondrial activity would lead to significantly improved embryo quality.Reproduction (2016) 152 R247-R261

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Section: Mitochondrial Signallingmentioning

confidence: 99%

The embryonic stress response to in vitro culture: insight from genomic analysis

Cagnone

Sirard

2016

Reproduction

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“…Very recently, a range of new molecular genetics technologies including chip-based single cell RNA sequencing and more efficient quantitative PCR methods have been used to quantitate genomic and mitochondrial DNAs found in spent embryo media (323). They show differences between intact vs fragmented embryos, thus highlighting a potential new indicator of developmental competence.…”

Section: Newer Candidates In the Embryo Secretomementioning

confidence: 99%

Soluble Ligands and Their Receptors in Human Embryo Development and Implantation

et al. 2015

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Extensive evidence suggests that soluble ligands and their receptors mediate human preimplantation embryo development and implantation. Progress in this complex area has been ongoing since the 1980s, with an ever-increasing list of candidates. This article specifically reviews evidence of soluble ligands and their receptors in the human preimplantation stage embryo and female reproductive tract. The focus will be on candidates produced by the human preimplantation embryo and those eliciting developmental responses in vitro, as well as endometrial factors related to implantation and receptivity. Pathways to clinical translation, including innovative diagnostics and other technologies, are also highlighted, drawing from this collective evidence toward facilitating joint improvements in embryo quality and endometrial receptivity. This strategy could not only benefit clinical outcomes in reproductive medicine but also provide broader insights into the peri-implantation period of human development to improve fetal and neonatal health.

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“…Palini et al (23) reported the observation of the existence of DNA in the blastocoele fluid, Gianaroli et al (24) performed a pilot study on chromosome screening using blastocentesis, and Stigliani et al (25,26) observed genomic and mitochondria DNA contents in the culture medium, which were correlated with embryo quality. Wu et al (27) reported the PCR detection of the secreted genomic DNA in the culture medium for preimplantation…”

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confidence: 99%

Noninvasive chromosome screening of human embryos by genome sequencing of embryo culture medium for in vitro fertilization

Fang

Chen

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

193

218

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Preimplantation genetic screening (PGS) is widely used to select in vitro-fertilized embryos free of chromosomal abnormalities and to improve the clinical outcome of in vitro fertilization (IVF). A disadvantage of PGS is that it requires biopsy of the preimplantation human embryo, which can limit the clinical applicability of PGS due to the invasiveness and complexity of the process. Here, we present and validate a noninvasive chromosome screening (NICS) method based on sequencing the genomic DNA secreted into the culture medium from the human blastocyst. By using multiple annealing and looping-based amplification cycles (MALBAC) for whole-genome amplification (WGA), we performed next-generation sequencing (NGS) on the spent culture medium used to culture human blastocysts (n = 42) and obtained the ploidy information of all 24 chromosomes. We validated these results by comparing each with their corresponding whole donated embryo and obtained a high correlation for identification of chromosomal abnormalities (sensitivity, 0.882, and specificity, 0.840). With this validated NICS method, we performed chromosome screening on IVF embryos from seven couples with balanced translocation, azoospermia, or recurrent pregnancy loss. Six of them achieved successful clinical pregnancies, and five have already achieved healthy live births thus far. The NICS method avoids the need for embryo biopsy and therefore substantially increases the safety of its use. The method has the potential of much wider chromosome screening applicability in clinical IVF, due to its high accuracy and noninvasiveness.

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Mitochondrial DNA content in embryo culture medium is significantly associated with human embryo fragmentation

Abstract: ClinicalTrials.gov Identifier: NCT01397136.

Cited by 128 publications

References 51 publications

The embryonic stress response to in vitro culture: insight from genomic analysis

The embryonic stress response to in vitro culture: insight from genomic analysis

Soluble Ligands and Their Receptors in Human Embryo Development and Implantation

Noninvasive chromosome screening of human embryos by genome sequencing of embryo culture medium for in vitro fertilization

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