According to co-corresponding author Zhen Liu of the Chinese Academy of Sciences (CAS) in Shanghai, 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,” Liu said.
Co-corresponding author Qiang Sun, also of CAS, added that the 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,” Sun explained.
Creating Embryo-like Structures from Macaque Stem Cells
The researchers started by exposing macaque embryonic stem cells to growth factors in cell culture, which induced the formation of embryo-like structures called blastoids. When studied under a microscope, these blastoids displayed similar morphology to natural blastocysts. As they developed further in vitro, they formed arrangements that resembled the amnion and yolk sac, and started to form the types of cells that eventually make up the three germ layers of the body. Single-cell RNA sequencing revealed that the different types of cells within the structures had gene expression patterns similar to those in natural blastocysts or post-implantation embryos.
Transferring Blastoids into Female Monkeys
The blastoids were transferred into the uteruses of eight female monkeys, and in three of the eight, the structures implanted. This implantation resulted in the release of progesterone and chorionic gonadotropin, hormones normally associated with pregnancy. The blastoids also formed early gestation sacs, fluid-filled structures that develop early in pregnancy to enclose an embryo and amniotic fluid. However, they did not form fetuses, and the structures disappeared after about a week.
Future Research and Ethical Considerations
The investigators plan to focus on further developing the system of culturing embryo-like structures from monkey cells. Co-corresponding author Fan Zhou of Tsinghua University said that this will provide a useful model for future study, and that further application of monkey blastoids can help to dissect the molecular mechanisms of primate embryonic development.
The researchers acknowledge the ethical concerns surrounding this type of research but emphasize that there are still many differences between these embryo-like structures and natural blastocysts. Importantly, the embryo-like structures do not have full developmental potential. They note that for this field to advance, it is crucial to have discussions between the scientific community and the public.
By creating an embryo-like structure using monkey embryonic stem cells for the first time, the researchers aim to better understand early human development and organ formation. The structures were able to implant in the uteruses of female monkeys and elicit a hormonal response similar to pregnancy, as reported in the Cell Stem Cell journal.
As the blastoids developed in the lab, they began to develop in ways similar to natural embryos. Genetic sequencing revealed that the different types of cells in the structures had similar gene expression patterns to cells found in natural blastocysts and embryos.
The blastoids were transferred into the uteruses of eight female monkeys, with successful implantation in three of the monkeys. The implantation caused the monkeys to release hormones normally associated with pregnancy, and the blastoids also formed early gestation sacs that typically develop early in pregnancy to enclose an embryo. However, the structures did not form fetuses and disappeared after about a week.
As the investigators plan to further develop the system of culturing embryo-like structures from monkey cells, they acknowledge the ethical concerns surrounding their research. They emphasize that these blastoids are very different from natural embryos and cannot fully develop, highlighting the importance of dialogue between the scientific community and the public to advance this field.