Scientists grow mouse embryos in a mechanical uterus –

Scientists grow mouse embryos in a mechanical uterus

The mouse embryos appeared perfectly normal. All of his organs were developing as expected, along with his limbs and his circulatory and nervous systems. Their little hearts beat at a normal rate of 170 beats per minute.

But these embryos were not growing in a mother mouse. They were developed inside an artificial uterus, the first time such a feat has been accomplished, scientists reported Wednesday.

The experiments, at the Weizmann Institute of Sciences in Israel, were intended to help scientists understand how mammals develop and how genetic mutations, nutrients and environmental conditions can affect the fetus. But the work may one day raise profound questions about whether other animals, including humans, should or could be grown outside of a living womb.

In a study published in the journal Nature, Dr. Jacob Hanna described the extraction of embryos from the uteri of mice at five days of gestation and their growth for another six days in artificial uteri.

At that time, the embryos were approximately in the middle of their development; full gestation is about 20 days. A human being at this stage of development would be called a fetus. To date, Dr. Hanna and his colleagues have grown more than 1,000 embryos in this way.

“It really is a remarkable achievement,” said Paul Tesar, a developmental biologist at Case Western Reserve University School of Medicine.

Alexander Meissner, director of genome regulation at the Max Planck Institute for Molecular Genetics in Berlin, said that “getting here is amazing” and that the study was “a major milestone.”

But the investigation has already progressed beyond what the researchers described in the paper. In an interview, Dr. Hanna said that he and his colleagues had retrieved fertilized eggs from the oviducts of female mice just after fertilization, on day 0 of development, and cultured them in the artificial uterus for 11 days.

Until now, researchers were able to fertilize mammalian eggs in the laboratory and grow them for a short time. The embryos needed a living uterus. “Placental mammals develop locked in the uterus,” said Dr. Tesar.

That prevented scientists from answering fundamental questions about the early stages of development.

“The holy grail of developmental biology is understanding how a single cell, a fertilized egg, can produce all the specific cell types in the human body and grow to 40 trillion cells,” said Dr. Tesar. “Since the beginning of time, researchers have been trying to develop ways to answer this question.”

The only way to study tissue and organ development was to turn to species such as worms, frogs and flies that do not need a uterus, or to extract embryos from the uteri of experimental animals at different times, providing more like snapshots of development. than the video.

What was needed was a way to enter the uterus, observe and adjust development in mammals as it happened. For Dr. Hanna, that meant developing an artificial uterus.

He spent seven years developing a two-part system that includes incubators, nutrients, and a ventilation system. The embryos of the mice are placed in glass vials inside incubators, where they float in a special nutritive fluid.

The vials are attached to a wheel that turns slowly so that the embryos do not adhere to the wall, where they would deform and die. The incubators are connected to a ventilation machine that provides oxygen and carbon dioxide to the embryos, controlling the concentration of these gases, as well as the pressure and flow of the gas.

On day 11 of development, more than halfway through a mouse’s pregnancy, Dr. Hanna and her colleagues examined embryos, only the size of apple seeds, and compared them to those that develop in the uterus of live mice. . The lab embryos were identical, the scientists found.

At that time, however, the lab-grown embryos had become too large to survive without a blood supply. They had a placenta and a yolk sac, but the nutrient solution that fed them by diffusion was no longer sufficient.

Overcoming that hurdle is the next goal, Dr. Hanna said in an interview. You are considering using an enriched nutrient solution or an artificial blood supply that connects to the placentas of the embryos.

Meanwhile, the experiments attract our attention. The ability to keep embryos alive and developing in mid-pregnancy “is a gold mine for us,” said Dr. Hanna.

The artificial uterus may allow researchers to learn more about why pregnancies end in miscarriages or why fertilized eggs do not implant. Opens a new window on how genetic mutations or deletions affect fetal development. Researchers can observe how individual cells migrate to their final destinations.

The work is “a breakthrough,” said Magdalena Zernicka-Goetz, a professor of biology and biological engineering at Caltech. “It opens the door to a new era of developmental study in the experimental mouse model.”

A recent development provides another opportunity. Researchers have directly created mouse embryos from mouse fibroblasts (connective tissue cells) that produce early embryos without starting with a fertilized egg.

Combine that development with the work of Dr. Hanna, and “now you don’t need mice to study mouse embryo development,” Dr. Meissner said. Scientists can make all the embryos they need from connective tissue.

If scientists could produce embryos without fertilizing eggs and could study their development without a uterus, Dr. Meissner said, “you can escape the destruction of embryos.” There would be no need to fertilize mouse eggs just to destroy them in the course of the study.

But the work could eventually extend beyond mice. Two other articles published in Nature on Wednesday report on attempts that come close to creating early human embryos in this way. Of course, Dr. Meissner said, the creation of human embryos is years away, if allowed at all. And for now, international regulations prohibit studying human embryos after 14 days of fertilization.

In the future, said Dr. Tesar, “it is not unreasonable that we have the ability to develop a human embryo from fertilization to birth completely outside the womb.”

Of course, even the suggestion of this sci-fi setting is sure to horrify many. But these are the early days, with no guarantee that human fetuses can fully develop outside of the womb.

Even assuming they could, Dr. Tesar noted, “whether that’s appropriate is a question for ethicists, regulators, and society.”

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