Scientists Create Human Embryo Model Without Sperm or Egg

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Researchers at the Weizmann Institute have successfully generated an entity that bears a striking resemblance to an early human embryo, all without the need for sperm, eggs, or a womb.

The Weizmann Institute team achieved this milestone by creating an “embryo model” through the use of stem cells, resulting in a structure that closely mimics a genuine 14-day-old embryo. Remarkably, this model even produced hormones that yielded a positive result on a pregnancy test in laboratory settings.

The primary objective of developing embryo models is to provide a morally sound means of comprehending the earliest stages of human life.

The initial weeks following fertilization of an egg by sperm mark a period of significant transformation, as a cluster of undifferentiated cells evolves into a structure that eventually becomes recognizable in a fetal ultrasound.

This critical phase is a major contributor to miscarriages and birth defects, yet it remains poorly understood. As Professor Jacob Hanna of the Weizmann Institute of Science explains, “It’s a black box, and that’s not a cliche – our knowledge is very limited.”

Starting Material

Embryo research poses legal, ethical, and technical challenges, but a rapidly evolving field now seeks to replicate natural embryo development.

Described in the journal Nature, this research by the Israeli team represents the first “complete” embryo model that emulates all key structures emerging during early embryo development.

Professor Hanna describes it as “truly a textbook representation of a human day-14 embryo,” a feat never before accomplished. Instead of relying on sperm and eggs, the starting material consisted of naïve stem cells that were reprogrammed to possess the potential to develop into any tissue type in the human body.

These stem cells were then guided by chemicals to differentiate into four types of cells found in the earliest stages of the human embryo:

  • Epiblast cells, which eventually form the embryo or fetus.
  • Trophoblast cells, which develop into the placenta.
  • Hypoblast cells, which give rise to the supportive yolk sac.
  • Extraembryonic mesoderm cells.

A precise ratio of 120 of these cells was mixed, and scientists observed as approximately 1% of the mixture spontaneously self-assembled into a structure resembling, though not identical to, a human embryo. Professor Hanna commends the remarkable phenomenon, stating, “I give great credit to the cells – you have to bring the right mix and have the right environment, and it just takes off.”

Scientists Create Human Embryo Model Without Sperm or Egg

Ethical Implications and Potential Applications

The synthetic embryo models were allowed to mature until they resembled embryos 14 days after fertilization, a legal limit for many countries regarding standard embryo research.

Professor Hanna passionately provides a 3D tour of the embryo model’s “exquisitely fine architecture,” highlighting features like the trophoblast and cavities that transport nutrients from the mother’s blood to the developing fetus. The model also includes a yolk sac with functions akin to the liver and kidneys and a bilaminar embryonic disc, a hallmark of this stage of embryo development.

These embryo models hold the potential to aid scientists in understanding the emergence of different cell types, witnessing the earliest stages of organ development, and studying inherited or genetic diseases. Some discussions even revolve around improving in vitro fertilization (IVF) success rates by exploring why certain embryos fail or testing the safety of medications during pregnancy using these models.

While impressed with the progress, Professor Robin Lovell Badge from the Francis Crick Institute notes that the current 99% failure rate must be addressed. Understanding the reasons behind miscarriages or infertility would be challenging if the model cannot consistently assemble itself.

Legal Distinctions and Ethical Questions

The research also sparks debate about whether embryo development could be simulated beyond the 14-day stage, a move that would not be illegal in many countries since embryo models are legally distinct from embryos. However, as these models approach the likeness of actual embryos, ethical considerations intensify.

Professor Alfonso Martinez Arias of Pompeu Fabra University hails this research as “a most important piece of research” that constructs a faithful representation of the complete structure of a human embryo from stem cells, paving the way for studying the events leading to the formation of the human body plan.

The researchers emphasize that attempting a pregnancy using these embryo models would be unethical, illegal, and biologically impossible, as assembling the 120 cells goes beyond the point where an embryo could successfully implant into the uterine lining.

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