▎ WuXi AppTec content team editor
Recently, a scientific research team led by Japanese scientists published a paper in the journal Science, which brought important advances in reproductive medicine. Using the main animal model of biomedical research, the rat, as the experimental object, the researchers used stem cells to create "primitive germ cells" in vitro, and these cells can successfully produce functional sperm in the testicles of azoospermia rats, eventually giving birth to healthy offspring.
Mammalian sperm and eggs are gametes, and primitive germ cells (PGCs) can be regarded as their precursors, which mature in the body and undergo multiple stages of development, eventually forming fertilized eggs or viable sperm.
Over the past decade, scientists studying stem cells have made many attempts in mice, transforming mouse pluripotent stem cells into cells similar to primitive germ cells, known as primitive germ cell-like cells (PGCLC), in in vitro experiments, and inducing these cells to produce gametes. However, after the groundbreaking success of mouse experiments, there have been no success stories in other animals.
This time, the scientists finally achieved a new breakthrough in rats, obtaining primitive germ cells that can produce sperm from pluripotent stem cells, a progress that helps to deepen the understanding of the basic mechanisms of gamete production. What's more, the physiological characteristics of rats are more similar to those of humans than mice, which means that we are one step closer to applying this assisted reproductive technology in many fields such as medicine.
Image credit: 123RF
A team led by Professor Toshihiro Kobayashi of the University of Tokyo and Professor Masumi Hirabayashi of the Institute of Physiology (NIPS) developed a new method specifically for rat stem cells in this work. They found that culturing stem cells with spherical structures in a petri dish in a suspension state can transform them into mesoderm cells, as past studies of mouse stem cells suggest, a key state for efficiently producing primordial germ cells.
The experimental results show that these cells further exhibit the early characteristics of primitive germ cells, including gene expression patterns. In addition, cultured with support cells required during embryonic development, their growth state can also be close to that of the original germ cells in the middle of development.
▲Schematic diagram of the experimental process (Image source: Reference[2])
The scientists then transplanted these primitive germ cell-like cells produced by stem cells into the testicles of male rats without sperm. A few weeks later, it can be clearly seen by fluorescent labeling that sperm is produced in the curved seminal ducts of the animal's testicles!
The successful results of artificial insemination showed that these sperm had normal functions: the researchers injected them one by one into the eggs of unfertilized rats by microinjection, and then transplanted the fertilized eggs into female rats. The resulting rats can grow healthily and give birth to offspring normally.
Raw germ cells produced by stem cells in vitro produce sperm in the testicles, and female rats are given healthy, fertile offspring through artificial insemination (Image source: Reference[1])
The study authors conclude that the successful acquisition of rat models following mice will fill a gap in our understanding of the developmental characteristics of germ cells in various mammals, including humans, which is important for widespread applications for the production of germ cells in vitro.
Resources:
[1] Mami Oikawa et al., (2022) Functional primordial germ cell–like cells from pluripotent stem cells in rats. Science Doi: 10.1126/science.abl4412
[2] Functional primordial germ cell-like cells from pluripotent stem cells in rats. Retrieved Apr. 8, 2022, https://www.ims.u-tokyo.ac.jp/imsut/en/about/press/page_00042.html
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