Breakthrough! Scientists use rhesus monkey embryonic stem cells

  • According to recent research, in the 1970s, the average male had 99 million sperm per milliliter of sperm, but by 2011, that number had plummeted to 47 million, a 53% decrease. According to Shanna Swan, an environmental medicine and public health professor at Mount Sinai's Icahn School of Medicine, men may be "spermless" by 2045 if the current trend continues.


    It's impossible to say whether or not this assumption is sensational, but male infertility has become a global health issue. Infertility affects as least 15% of couples globally, with men accounting for half of those affected. Male infertility can be caused by genetic abnormalities, environmental pollutants, accidents, or therapeutic side effects such as alkalizing chemotherapy. Infertility has no known remedy.


    A team of researchers led by the University of Georgia employed embryonic stem cells from non-human primates (NHPs) to develop viable sperm cells in vitro for the first time in a report published in Fertility and Sterility Science. The study is a big step forward in reproductive and developmental biology, with the potential to treat infertility in men who are unable to generate viable sperm.


    The team, along with researchers from East China Normal University and others, has previously established the ability to generate advanced spermatogenic cells from mouse stem cells, although the mechanism of sperm generation in rodents differs significantly from that in humans. Prior to starting this project, the researchers were unsure whether the technique could be applied to humans.


    Rhesus monkeys are an ideal and required model for investigating male infertility therapies based on stem cell technologies since they have similar reproductive mechanisms to humans and their spermatogenesis is more akin to humans in terms of kinetics.


    Researchers have demonstrated for the first time in rhesus monkey experiments that functional haploid sperm can be differentiated entirely in vitro from non-human primate pluripotent stem cells in this new study. This finding is a significant step forward in the development of male germ cells in vitro.


    However, according to the researchers, there are still some problems. They discovered that germ cell differentiation driven by spermatogonial stem cells does not elevate the expression of the TET3 gene (normally expressed in mature sperm) to the levels observed in rhesus monkey sperm. That is, the sperm-like cells produced are immature, similar to spherical sperm in primates. As a result, it is incapable of activating mature oocytes on its own.


    The addition of activating factors and purified TET3 protein enhanced the efficiency of generating healthy embryos to overcome this barrier to fertilization, the researchers discovered.


    In conclusion, this study shows that NHP pluripotent stem cells can differentiate into spermatogenic cell lineages, including sperm-like cells that can fertilize NHP oocytes and develop to the blastocyst stage, as well as some of the meiotic mechanisms involved in generating haploid round spermatocyte-like cells in vitro.


    The researchers believe that by learning more about the causes of spermatogenesis arrest in infertile men, they will be able to bridge the gap between reproductive and developmental biology.


    Professor Charles Easley of the University of Georgia School of Public Health, the project's head and principal investigator, said, "this study is a significant step toward demonstrating that stem cell technology is translatable. For our research, we're employing a species that's much closer to us, and we've had success generating healthy embryos."


    The researchers want to test if these in vitro-generated sperm cells can develop healthy embryos in surrogate rhesus monkeys this fall, which is the next essential step. If this stage is successful, the research team will use sperm-like cells produced from rhesus skin cells to recreate the procedure.