Human embryo development in the highest resolution image ever

Live human blastocyst with dye image.

Live human blastocyst with dye image.

A living human embryo imaged using the fluorescent dyes SPY650-DNA (blue) and SPY555-actin (pink).Credit: Robin M. Skory, Ana Domingo-Muelas

Researchers have captured the most detailed images of developing human embryos in real time, using two common laboratory tools – fluorescent dyes and laser microscopy.

The technique, explained in Cell On July 51Allows researchers to study important events in the first few days of development without genetically modifying the embryos, which previously limited the use of certain imaging techniques in human embryos, due to ethical concerns.

Nicolas Plachta, a cell biologist at the University of Pennsylvania in Philadelphia and a co-author said, “This is the first time we have been able to image a human embryo at an early stage of development with cellular resolution.” “We can see single cells and how they interact with each other as they form an embryo before implantation.”

As well as providing new tools for researchers, imaging techniques can lead to the development of methods to non-invasively screen embryos conceived through. in vitro Fertilization (IVF).

Fluorescent dye

Researchers usually have to study human embryos using post-mortem samples, because many tools for labeling living cells involve genetically modifying them to produce fluorescent proteins.

Plachta and his colleagues developed a solution using a fluorescent dye that can only be added to the sample to mark specific cell structures.

The embryos used in this study were donated for research through an IVF clinic. They’re in the early stages of development — made up of only 60 to 100 cells each — and don’t yet have fully formed tissues or organs, Plachta says.

The researchers used SPY650-DNA, a fluorescent dye that labels genomic DNA, and SPY555-actin, which labels the F-actin protein that makes up the cell’s skeleton. They then visualized dozens of living larvae during the first 40 hours of development using a powerful laser scanning microscope.

“We can see those cells divide and separate chromosomes, and we can also capture chromosome segregation defects in real time,” Plachta said.

For example, researchers have observed that cells in the outermost layer of the embryo, called the trophectoderm, lose some of their DNA during a stage of cell replication called interphase – in which cells are making copies of their DNA.

Such errors can be linked to chromosomal abnormalities such as aneuploidy, a condition marked by extra or missing chromosomes in the early embryo and associated with pregnancy loss and implantation failure.

“Knowing when aneuploidies occur gives us the opportunity to intervene and try to solve the problem,” said Zev Williams, an obstetrician at Columbia University in New York City. The latest images reveal the first days of embryo development “with unprecedented clarity”, he added.

Not like a mouse

Researchers can also compare key events in human and mouse embryos – which are often used as models to study fetal development. They noted several important differences. For example, a process called compaction, which involves changes in cell shape, begins at the 12-cell stage in human embryos compared to the 8-cell stage in mice; The process is also more inconsistent in human embryos, which leads to changes in the formation of inner and outer cells.

Sade Clayton, a biologist at Washington University in St. “Detecting these small changes is what makes this paper so novel,” said Louis, Missouri. “These small differences are real [translate to] A big difference in the development of the womb.”

The authors hope to build on this research by photographing human embryos for longer periods of time, using low-intensity laser microscopy, and incorporating other dyes that can label different structures, such as cell membranes.

The technique may have clinical applications one day, Plachta said. “In the future, we can use this kind of live imaging to monitor embryos non-invasively in the clinic,” he said. This can be part of a test to identify the “best potential embryo” before implantation, he added.

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