Fundamental Science: The embryo generated without sperm or egg

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One of the most fascinating phenomena in nature is that extremely complex animals like humans are formed from a single cell, the zygote, the result of the junction of an egg with a sperm. About 30 hours after fertilization, the zygote begins to divide and, as the divisions progress, the cells acquire specific destinations: some will form all the cell types in the human body; others, supporting and nourishing tissues such as the placenta.

Embryos produced by in vitro fertilization are transferred to the uterus around the fifth day, as it is at the end of this first week that the implantation process begins, in which the embryo will need to seek oxygen and nutrient in the maternal blood vessels. In the following days, some of the most important events of embryonic development will take place, and at the same time the most unknown.

After implantation, the cells of the future embryo divide into three layers that will give rise to our approximately 200 cell types. Little understood in humans, this phenomenon, gastrulation, is extensively studied in embryos of animals such as chickens, fish and flies. The importance is such that Lewis Wolpert, a well-known embryologist, said four decades ago that it is not birth, marriage or death, but gastrulation, the most important moment we go through.

It is also in these first weeks that half of the cases of miscarriage are concentrated. Details of this stage, a true “black box of human embryonic development”, cannot be directly observed in the mother’s uterus, nor can they be mimicked in the laboratory, given the need for the embryo to implant itself in order to move forward. In the last five years, however, many advances have been made, allowing human embryos to be cultured beyond six days.

From surpluses donated by couples who have undergone fertilization in vitro, the group led by Professor Magdalena Zernicka-Goetz, from the University of Cambridge, developed a special form of culture in the laboratory that made it possible to implant and develop embryos for an additional week, even without the support of maternal tissue. New microscopy techniques made it possible to film the growth of the embryo during this period, showing how the layers of cells separate, and also revealed some differences between gastrulation in humans and what we knew about other mammals, such as mice. Embryo cultivation was interrupted on the 13th day due to ethical norms existing in several countries, which already prohibited the cultivation of human embryos for more than two weeks, even before this was possible in technological terms.

This year, another milestone was reached: the production of mouse embryos without using sperm and eggs. This achievement has been a great desire in the academic community for decades and was achieved by the Zernicka-Goetz group and the team of Jacob Hanna from Israel. So-called embryoids or “synthetic embryos” are generated by the simultaneous cultivation of three types of stem cells: one type that forms all the tissues of the mouse’s body and another two that form structures attached to the embryo.

Cultured cells self-organize into structures very similar to embryos, with the same body axes, brain regions, a primitive gut and even a beating heart. The embryoids were viable for eight days, about half the gestational period of a mouse. The production protocols of these structures will still be improved, aiming to increase efficiency, but they are already an impressive advance in this field.

All these recent scientific discoveries will help us to understand in the coming years why some pregnancies do not evolve, and what to do to avoid miscarriages. It will also be possible to study the origin of various congenital diseases and design techniques to obtain biological tissues or entire organs using, for example, the patient’s own skin cells. With adequate investments, we will have great progress in the science of human reproduction, always going hand in hand with bioethical precepts.

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Rossana Soletti is a PhD in morphological sciences and a professor at the Federal University of Rio Grande do Sul.

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