On October ^31st, 2019, scientists reported the establishment of an in vitro culture (IVC) system which supported the continuous development of monkey embryos beyond early gastrulation and to 20 days post fertilization.

This research, conducted by scientists from Dr. WANG Hongmei's group and Dr. LI Lei's group from the Institute of Zoology of the Chinese Academy of Sciences, and Dr. ZHENG Ping's group from the Kunming Institute of Zoology of CAS, has been published in an rticle entitled "In vitro culture of cynomolgus monkey embryos beyond early gastrulation" in Science.

Peri-implantation embryonic development is a critical process during which the embryo establishes a close relationship with maternal uterus. The abnormal development of human peri-implantation embryos appears to be correlated with the frequencies of woman reproductive disorders and human major structural malformations in central nervous system, heart and limbs. However, the knowledge of human peri-implantation embryonic development and gastrulation is very limited.

Since these events happen within the uterus, the development and gastrulation have been very difficult to observe and analyze. Thus, IVC systems may serve as a powerful tool to solve this problem. Though significant advances have been made in murine development with mouse embryo IVC systems, early embryogenesis in the rodent is distinct from that in primates.

In 2016, Zernicka-Goetz's lab and Brivanlou's lab cultured human embryos in vitro for 12-13 days, leading to extensive discussions worldwide. Because many governments and international organizations have recommended that human embryos should not be allowed to grow beyond 14 days in vitro, a non-human primate embryo IVC system is urgently needed to understand the gastrulation of early primate embryogenesis, and the related problems and diseases that arise during early human development.

In this study, the scientists reported the establishment of an IVC system which supported the continuous development of monkey embryos beyond early gastrulation and to 20 days post fertilization. They optimized an IVC system for the culture of mouse blastocysts beyond early postimplantion stageb and they used this optimized system to culture cynomolgus monkey embryos to 20 days. At d.p.f. 13-14, a bilaminar disc-like structure appeared in ~27.7% of the IVC embryos. Single-cell RNA-seq analyses showed that the IVC embryos were similar to their in vivo counterparts in gene expression profiles and cell types.

In addition, this study revealed the molecular signatures of several cell types of primate early post-implantation embryos, including amnion cells.

Altogether, this study provides compelling evidence supporting that the cynomolgus monkey embryos can develop beyond early gastrulation and to 20 days post fertilization in their IVC system.

This study provides novel information on cell lineage specification during primate early post-implantation development. In combination with CRISPR-Cas9-mediated gene editing and cell lineage tracing, this system will accelerate our understanding of the mysterious dynamics of early embryonic development in primates, with possible relevance to human early embryonic development and diseases.

The study was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences, the National Key R&D Program of China, the National Natural Science Foundation of China and the exchange program of State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences.

Monkey embryos grow in vitro beyond early gastrulation (Image by IOZ)