Ex Utero Embryogenesis

April 20, 2021

A group of Israeli researchers have grown mammalian embryos “ex utero”, that is outside the womb: they grew mice in an artificial womb for half the animal’s natural gestation period. Humans are mammalians: are humans next? The answer is yes.

A group of Israeli researchers have succeeded in growning mammalian embryos “ex utero”, that is outside the natural womb. They grew mice embyos in an artificial womb for as long as 12 days (the longest time frame to date), which is half the animal’s natural gestation period.

The recent paper – entitled, “Ex utero mouse embryogenesis from pre-gastrulation to late organogenesis” and published in the journal “Nature” – presents “highly effective platforms for the ex utero culture of post-implantation mouse embryos, which enable the appropriate development of embryos from before gastrulation until the hindlimb formation stage”.

Authors write: “The mammalian body plan is established shortly after the embryo implants into the maternal uterus, and our understanding of post-implantation developmental processes remains limited. … Histological, molecular and single-cell RNA sequencing analyses confirm that the ex utero cultured embryos recapitulate in utero development precisely. … The establishment of a system for robustly growing normal mouse embryos ex utero from pre-gastrulation to advanced organogenesis represents a valuable tool for investigating embryogenesis, as it eliminates the uterine barrier and allows researchers to mechanistically interrogate post-implantation morphogenesis and artificial embryogenesis in mammals.”

Israeli scientists grew the mouse embryos by adding blood serum from human umbilical cords, agitating them in glass jars, and pumping in a pressurized oxygen mixture. Pressurized oxygen helps to feed the developing cells, pushing through with pressure where nature would build a circulatory system. As reported by MIT Tech Review – a media company explaining the newest technologies and their commercial, social and political impacts – the mouse embryos died after they became too large for the oxygen to diffuse through them, since they lack the natural blood supply a placenta could provide.

Researchers were not able to grow the mice starting from a fertilized egg all the way to day 12. Instead, they collected 5-day-old embryos from pregnant mice and moved them into the incubator system, where they lived another week. The mouseembryos develop correctly only if they can be attached to an actual mouse uterus, at least for a brief time, and the scientists are now working on adapting the procedure to develop the mice entirely in vitro.

The recent Israeli paper opens a “scientific window” onto the early embryo, which is normally hidden inside the uterus. The human equivalent of 12-day-old mice would be a first-trimester embryo, and researchers will want to develop human embryos this way too. Lead author Jacob Hanna – a biologist at the Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel – declared: “It took six years of very intense work to get this system to where it is. This sets the stage for other species.”

“I hope”, Hanna continued, “that it will allow scientists to grow human embryos until week five. I do understand the difficulties. You are entering the domain of abortions. So I would advocate growing it until day 40 and then disposing of it. Instead of getting tissue from abortions. We need to see human embryos gastrulate and form organs and start perturbing it. The benefit of growing human embryos to week three, week four, week five is invaluable. I think those experiments should at least be considered. If we can get to an advanced human embryo, we can learn so much.”

According to MIT Technology Review “human embryos could be next – raising huge new ethical questions. Growing human embryos in the lab for that long, deep into the first trimester, would put science on a collision course with the abortion debate. Hanna believes lab-grown embryos could be a research substitute for tissue derived from abortions, and possibly a source of tissue for medical treatments as well.”

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