Human oocyte developmental potential is predicted by mechanical properties within hours after fertilization

Abstract

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 demonstrate that there are significant differences between the transcriptomes of viable and non-viable zygotes, especially in expression of genes important for oocyte maturation. In addition, we show that low-quality oocytes may undergo insufficient cortical granule release and zona-hardening, causing altered mechanics after fertilization. Our results suggest that embryo potential is largely determined by the quality and maturation of the oocyte before fertilization, and can be predicted through a minimally invasive mechanical measurement at the zygote stage.

Does the transfer of a poor quality embryo together with a good quality embryo affect the In Vitro Fertilization (IVF) outcome?

“…This might partially explain our result regarding the pregnancy rate with poor quality embryos. Perhaps more advanced methods to evaluate embryos, such as time lapse and genetic screening or pre-gestational screening (PGS) [10, 11] will provide a better definition of good and poor quality embryos and help to better predict viable pregnancies.…”

Mosaicism in Preimplantation Human Embryos: When Chromosomal Abnormalities Are the Norm

“…Oscillation of cyclins and cyclin-dependent kinases (Cdks)—essential regulators of cell cycle progression—thus occurs through mechanisms independent of transcription and is significantly dampened [22]. Recent studies have used single-cell expression profiling to identify maternal-effect genes differentially expressed in aneuploid/euploid and arresting/normally-developing embryos [23, 24]. Intriguingly, zygotes destined to arrest based on mechanical properties exhibited downregulation of genes involved in cell cycle regulation and mitotic checkpoint control, including CDK1 , CDK2 , CHEK2 , BUB1 , BUB3, BRCA1 , and ATR [24].…”

“…Knockout of several cohesion genes (including SMC3 , RAD21 , STAG1 , NIPBL , and PLK1 ) causes early embryonic arrest in mouse models [67] while mutation and dysregulation of these genes contributes to Cornelia de Lange syndrome, Roberts syndrome, and several types of cancer [67, 68, 69]. Notably, zygotes predicted to give rise to arrested embryos (based on mechanical parameters) exhibit differential expression of several cohesion genes including SMC3 and securin, providing preliminary evidence of their importance in maintaining mitotic fidelity during the cleavage stage [24]. Given these observations, the role of cohesion defects in contributing to embryonic mosaicism deserves further attention.…”

Mechanophysical Cues in Extracellular Matrix Regulation of Cell Behavior

“…Knowing the mechanism of this comprehensive step could be useful in developing a plan for regenerative medicine and tissue engineering . The most influential findings in the biological field is that the factors responsible for cell behavior promotion are not only genetic or biochemical but also mechanical . The mechanical effects contained in cytoskeleton activity such as cell migration and the actin‐myosin network have been an important factor for experimentation using different types of nanotechnologies …”