Extracellular vesicles, microRNA and the preimplantation embryo: non-invasive clues of embryo well-being

Hawke, David Connor; Watson, Andrew J.; Betts, Dean H.

doi:10.1016/j.rbmo.2020.11.011

Cited by 18 publications

(24 citation statements)

References 111 publications

(246 reference statements)

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“…Extracellular miRNAs and extracellular vesicles (EVs) of embryonic origin are of particular interest owing to their potential application in the ongoing initiative aimed at improving embryo transfer outcomes during assisted reproduction [reviewed by Hawke et al (2020)]. Clinical studies are now reporting detection of nearly 150 miRNAs within spent media microdroplets used to culture human blastocysts (Russell et al, 2020); miRNAs have also been identified within the spent media used to culture bovine (Kropp et al, 2014;Kropp and Khatib, 2015;Gross et al, 2017b;Lin et al, 2019a,b) and murine (Heidari et al, 2019) pre-implantation embryos.…”

Section: Introductionmentioning

confidence: 99%

Murine Blastocysts Release Mature MicroRNAs Into Culture Media That Reflect Developmental Status

et al. 2021

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Extracellular microRNA (miRNA) sequences derived from the pre-implantation embryo have attracted interest for their possible contributions to the ongoing embryonic–uterine milieu, as well as their potential for use as accessible biomarkers indicative of embryonic health. Spent culture media microdroplets used to culture late-stage E4.0 murine blastocysts were screened for 641 mature miRNA sequences using a reverse transcription–quantitative polymerase chain reaction–based array. We report here 39 miRNAs exclusively detected in the conditioned media, including the implantation-relevant miR-126a-3p, miR-101a, miR-143, and miR-320, in addition to members of the highly expressed embryonic miR-125 and miR-290 families. Based on these results, an miRNA panel was assembled comprising five members of the miR-290 family (miR-291-295) and five conserved sequences with significance to the embryonic secretome (miR-20a, miR-30c, miR-142-3p, miR-191, and miR-320). Panel profiling of developing embryo cohort lysates and accompanying conditioned media microdroplets revealed extensive similarities in relative quantities of miRNAs and, as a biomarker proof of concept, enabled distinction between media conditioned with differently staged embryos (zygote, 4-cell, and blastocyst). When used to assess media conditioned with embryos of varying degrees of degeneration, the panel revealed increases in all extracellular panel sequences, suggesting cell death is an influential and identifiable factor detectable by this assessment. In situ hybridization of three panel sequences (miR-30c, miR-294, and miR-295) in late-stage blastocysts revealed primarily inner cell mass expression with a significant presence of miR-294 throughout the blastocyst cavity. Furthermore, extracellular miR-290 sequences responded significantly to high centrifugal force, suggesting a substantial fraction of these sequences may exist within a vesicle such as an exosome, microvesicle, or apoptotic bleb. Together, these results support the use of extracellular miRNA to assess embryonic health and enable development of a non-invasive viability diagnostic tool for clinical use.

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Section: Introductionmentioning

confidence: 99%

Murine Blastocysts Release Mature MicroRNAs Into Culture Media That Reflect Developmental Status

et al. 2021

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“…These associations enhance the stability of extracellular sncRNAs, allowing for their detection and use as biomarkers. Previous studies have profiled the sncRNA population in spermatozoa, seminal plasma, follicular fluid, and embryo culture medium, with an emphasis on identifying specific sets of sncRNAs whose relative abundance show strong correlation with reproductive diseases, infertility, or embryo developmental potential [ 119 , 210 , 211 , 212 , 213 ].…”

Section: Sncrnas In Sperm Seminal Plasma Follicular Fluid and Embryo Culture Medium As Biomarkers For Fertility And Embryo Development Pomentioning

confidence: 99%

“…Embryos cultured in vitro also produce extracellular vesicles that contain sncRNAs [ 230 ]. With constantly improving technologies, various miRNAs, piRNAs, and tRNA halves (tiRNAs) are detectable in spent culture media and suggest indicative potential for embryo quality, such as ploidy and pregnancy outcomes [ 212 , 213 , 230 , 231 , 232 , 233 , 234 , 235 ].…”

Section: Sncrnas In Sperm Seminal Plasma Follicular Fluid and Embryo Culture Medium As Biomarkers For Fertility And Embryo Development Pomentioning

confidence: 99%

Small Noncoding RNAs in Reproduction and Infertility

et al. 2021

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Infertility has been reported as one of the most common reproductive impairments, affecting nearly one in six couples worldwide. A large proportion of infertility cases are diagnosed as idiopathic, signifying a deficit in information surrounding the pathology of infertility and necessity of medical intervention such as assisted reproductive therapy. Small noncoding RNAs (sncRNAs) are well-established regulators of mammalian reproduction. Advanced technologies have revealed the dynamic expression and diverse functions of sncRNAs during mammalian germ cell development. Mounting evidence indicates sncRNAs in sperm, especially microRNAs (miRNAs) and transfer RNA (tRNA)-derived small RNAs (tsRNAs), are sensitive to environmental changes and mediate the inheritance of paternally acquired metabolic and mental traits. Here, we review the critical roles of sncRNAs in mammalian germ cell development. Furthermore, we highlight the functions of sperm-borne sncRNAs in epigenetic inheritance. We also discuss evidence supporting sncRNAs as promising biomarkers for fertility and embryo quality in addition to the present limitations of using sncRNAs for infertility diagnosis and treatment.

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“…Elective single embryo transfer is a method where the embryo with the best chance for survival is selected for implantation. With the selection of a single embryo, eSEP minimizes the complications that arise from a multiple pregnancy [ 3 ]. While the eSEP method lowers the number of viable pregnancies in comparison with double embryo transfer in a fresh cycle of in vitro fertilization (IVF), an additional frozen eSEP cycle minimizes this difference [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…The best embryo is frequently selected based on morphological assessment, as this is a cost-effective, rapid, and non-invasive technique [ 3 , 5 ]. While it is widely used, this technique does not account for the possibility of genetic abnormalities, since there is no correlation between morphological traits and genetic material [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Non-Invasive Preimplantation Genetic Testing for Aneuploidy and the Mystery of Genetic Material: A Review Article

Tomic

Bokal

Štimpfel

2022

IJMS

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This review focuses on recent findings in the preimplantation genetic testing (PGT) of embryos. Different preimplantation genetic tests are presented along with different genetic materials and their analysis. Original material concerning preimplantation genetic testing for aneuploidy (PGT-A) was sourced by searching the PubMed and ScienceDirect databases in October and November 2021. The searches comprised keywords such as ‘preimplantation’, ‘cfDNA’; ‘miRNA’, ‘PGT-A’, ‘niPGT-A’, ‘aneuploidy’, ‘mosaicism’, ‘blastocyst biopsy’, ‘blastocentesis’, ‘blastocoel fluid’, ‘NGS’, ‘FISH’, and ‘aCGH’. Non-invasive PGT-A (niPGT-A) is a novel approach to the genetic analysis of embryos. The premise is that the genetic material in the spent embryo culture media (SECM) corresponds to the genetic material in the embryo cells. The limitations of niPGT-A are a lower quantity and lesser quality of the cell-free genetic material, and its unknown origin. The concordance rate varies when compared to invasive PGT-A. Some authors have also hypothesized that mosaicism and aneuploid cells are preferentially excluded from the embryo during early development. Cell-free genetic material is readily available in the spent embryo culture media, which provides an easier, more economic, and safer extraction of genetic material for analysis. The sampling of the SECM and DNA extraction and amplification must be optimized. The origin of the cell-free media, the percentage of apoptotic events, and the levels of DNA contamination are currently unknown; these topics need to be further investigated.

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Extracellular vesicles, microRNA and the preimplantation embryo: non-invasive clues of embryo well-being

Cited by 18 publications

References 111 publications

Murine Blastocysts Release Mature MicroRNAs Into Culture Media That Reflect Developmental Status

Murine Blastocysts Release Mature MicroRNAs Into Culture Media That Reflect Developmental Status

Small Noncoding RNAs in Reproduction and Infertility

Non-Invasive Preimplantation Genetic Testing for Aneuploidy and the Mystery of Genetic Material: A Review Article

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