Generation of Monkey Blastoids Using Optimized Protocol

Human embryo development and early organ development remain unclear due to ethical concerns about using embryos for research and a scarcity of materials to investigate.

A team of researchers from China reveals for the first time the development of embryo-like structures from monkey embryonic stem cells. The researchers also implanted these embryo-like structures into the uteruses of female monkeys and discovered that they could implant and evoke a hormonal response akin to pregnancy.

The study was published on April 6^th, 2023 in the journal Cell Stem Cell.

The molecular mechanisms of human embryogenesis and organogenesis are largely unclear. Because monkeys are closely related to humans evolutionarily, we hope the study of these models will deepen our understanding of human embryonic development, including shedding light on some of the causes of early miscarriages.”

Zhen Liu, Study Co-Corresponding Author, Chinese Academy of Sciences

“This research has created an embryo-like system that can be induced and cultured indefinitely. It provides new tools and perspectives for the subsequent exploration of primate embryos and reproductive medical health,” states co-corresponding author Qiang Sun, also of CAS.

The researchers began with macaque embryonic stem cells that had been exposed to a variety of growth stimuli in cell culture. For the first time, non-human primate cells were used to induce stem cells to produce embryo-like structures.

Under a microscope, the embryo-like formations, also known as blastoids, were discovered to exhibit morphology comparable to natural blastocysts. They produced configurations that resembled the amnion and yolk sac as they matured in vitro.

The blastoids also began to create the types of cells that would later make up the body’s three germ layers. The numerous types of cells detected within the structures displayed similar gene expression patterns to cells found in natural blastocysts or post-implantation embryos, according to single-cell RNA sequencing.

The blastoids were subsequently placed in the uteruses of eight female monkeys, with three of the eight surviving. This implantation caused the release of progesterone and chorionic gonadotropin, both of which are generally associated with pregnancy.

Early gestation sacs, fluid-filled structures that emerge early in pregnancy to contain an embryo and amniotic fluid, were also created by the blastoids. They did not, however, develop fetuses, and the structures disappeared after about a week.

The researchers intend to focus their future efforts on improving the technology for culturing embryo-like structures from monkey cells.

This will provide us with a useful model for future study. Further application of monkey blastoids can help to dissect the molecular mechanisms of primate embryonic development.”

Fan Zhou, Study Co-Corresponding Author, Tsinghua University

The researchers acknowledge the ethical concerns that this type of research raises but emphasize that there are still significant differences between these embryo-like structures and natural blastocysts. Notably, the embryo-like formations lack full developmental potential. They stress the importance of discussions between the scientific community and the general people in order for this field to advance.