In Indian mythology, there has been a story where pieces of embryo’s flesh when kept in the bottles gave birth to babies. Whether this myth is true or not is not the scope of this article but the phenomenon called “origin of life” has always intrigued us. The human brain has always been fascinated to explore the plethora of developmental events from the embryonic stage to organ formation, which are complex and not yet fully understood.
In the past, scientists have used species such as worms and flies that do not require uterus; or isolating mouse embryos at different time points during development to get an overall snapshot. Many researchers worldwide are trying to develop novel strategies to grow mouse and human early fetal cells in a dish. In this direction, Magdelena Zernika Gotz and colleagues from Caltech Institute of Technology and the University of Cambridge have established in-vitro culture conditions to grow fertilized egg from mouse and human embryos in a dish without oxygen and nutritional support from placental tissue. But, again one of the major hurdles faced in the field was the need for the uterus to grow these in-vitro grown early embryos in a dish for the long term.
Scientists have been trying to mimic the in-utero culture condition since the 1930s, comprising of culturing embryos in a bottle with static, rotating, or circulatory bottle systems. However, these platforms remain highly inefficient as the embryo develops abnormalities as early as 24h in culture conditions. So, there is a need to establish stable culture conditions and methods to grow these embryos outside in a bottle. Recently, a remarkable study has been published in Nature by Jacob Hanna and colleagues, from Weismann Institute Israel, where they developed a rotating bottle-like mechanical womb and have grown mouse embryos outside the uterus. They isolated 5-day old mouse embryos and allow them to grow until day 11 in the mechanical bottles. These embryos are halfway through development as the full gestation period in mouse is 20 days. During the time in the mechanical womb, the embryo grew normally and developed a healthy normal tiny beating heart, limbs, and also the nervous system.
This study is one of the major milestones in early embryonic development. This would perhaps allow researchers worldwide to answer essential questions about the developmental period. It was a major prerequisite for developing a platform to probe inside the uterus, watch them alive and understand better the need for a uterus. Dr. Hanna and colleagues have spent years developing this artificial womb, consisting of incubators and ventilator systems. The embryo was isolated on day 5 and kept in the glass bottle inside the incubator, where they bathed in a special nutrient fluid and were slowly spinning to prevent attachment to the wall. These rotating bottles helped the tiny embryos with sufficient oxygen and atmospheric pressure. But, maintaining the atmospheric pressure and oxygen saturation level was the most challenging part, according to Dr. Hanna. It was a two-step process where they first isolated embryos from a pregnant mouse before attachment to the uterus and grew on lab dishes from days 5 to 7 of development. This is when an embryo undergoes a process called gastrulation, in which a hollow ball of cells gives rise to a multicellular structure having a specific tissue identity. On day 8, the embryos were transferred into rotating glass bottles and grown till day 11. Researchers also compared these lab-grown embryos with the embryo from the uterus and found that they were identical. In later days, these
omgomg onion lab-grown embryos became quite big to survive without blood supply as the nutrient solution in which they were grown was not sufficient. For future studies, Dr. Hanna plan to use artificial blood system or vascularization methods to grow these embryos for a longer duration in the rotating bottles.
In addition, Dr. Hanna’s team went one step ahead and depicted this methodology’s advantage by introducing genetic tags to certain cells in the mouse embryos and following them using a live-cell imaging technique. They also introduced a certain type of tagged human neural cells that were partly integrated into the mouse developing brain, demonstrating both normal and abnormal development. This methodology has opened new doors for researchers to learn about genetics and environmental causes for miscarriages during early pregnancies. It will also help in understanding why implantation fails in the uterus.
Dr. Hannah further plans to establish culture conditions to grow mouse embryos from single-cell fertilized egg to late-stage in the rotating bottles. This will in turn stop the need for sacrificing mice for laboratory experiments. Scientists have not yet attempted to grow human embryos in these rotating bottles but researchers are trying to study the human early development bypassing the need for the human fertilized egg. In this direction, Jose M. Polo from Montash University directly converted human skin cells to human blastocyst-like structures named as iBlastoids which were similar to the human early blastocyst when compared using a battery of cellular and molecular analysis.
It is not far when scientists can grow a mouse embryo from implantation to full gestation (day 0 to 20) outside the mother’s uterus. But still, researchers have to go a long way to grow human embryos entirely outside the womb. It will be interesting to perform these experiments with human embryos because we know very little about early human development, keeping in mind the experimental ethical concerns.
