With global rates of male infertility continuing to rise, a new study in spermatogonial stem cell research led by researchers at the University of Georgia (UGA) provides hope for future clinical therapies. McGowan Institute for Regenerative Medicine affiliated faculty members Kyle Orwig, PhD, Professor, OB/GYN and Reproductive Sciences, University of Pittsburgh School of Medicine, with secondary appointments in Microbiology and Molecular Genetics, Developmental Biology, and the Clinical and Translational Science Institute, and the founding Director of the Fertility Preservation Program of UPMC and the UPMC Magee Center for Reproduction and Transplantation, and Gerald Schatten, PhD, Director of the Pittsburgh Development Center, Professor of Obstetrics, Gynecology and Reproductive Sciences, Cell Biology, Bioengineering and Director of the Division of Developmental and Regenerative Medicine, are collaborators on this work.

The study, which was published recently in Fertility and Sterility Science, is the first to show that functional sperm cells can be made in a dish using primate embryonic stem cells.

“This is a major breakthrough towards producing stem cell-based therapies to treat male infertility in cases where the men do not produce any viable sperm cells,” said lead researcher Charles Easley, PhD, an associate professor in UGA’s College of Public Health.

Researchers used embryonic stem cells from rhesus macaque monkeys to generate immature sperm cells known as round spermatids, which they showed to be capable of fertilizing a rhesus macaque egg.

Scientists have been able to produce sperm-like cells using mouse stem cells, said Dr. Easley, but rodent sperm production is distinctly different than humans. Until this work, it wasn’t clear that this technology could ever work in humans.

“This is the first step that shows this technology is potentially translatable. We’re using a species that’s more relevant to us, and we’re having success in making healthy embryos,” said Dr. Easley.

Rhesus macaques share similar reproductive mechanisms to humans, making them an “ideal and necessary model for exploring stem cell-based therapies for male infertility,” the authors write.

Using a novel method, the researchers differentiated the cells into immature sperm cells known as round spermatids. Like immature spermatids in vivo, fertilization with in vitro spermatids requires activating the egg and the addition of other factors to enable the fertilized egg to develop into a healthy embryo.

This fall, the researchers plan to take the next critical step of implanting these embryos into a surrogate rhesus macaque to examine whether these embryos from in vitro spermatids can produce a healthy baby.

If that step is successful, the team will carry out the same process using spermatid-like cells derived from macaque skin cells.

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University of Georgia News Release


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Abstract (Blastocyst development after fertilization with in vitro spermatids derived from nonhuman primate embryonic stem cells. Sujittra Khampang, PhD, In Ki Cho, PhD, Kanchana Punyawai, PhD, Brittany Gill, BS, Jacqueline N. Langmo, BS, Shivangi Nath, PhD, Katherine W. Greeson, BS, Krista M. Symosko, BS, Kristen L. Fowler, MS, Siran Tian, BS, John P. Statz, BS, Alyse N. Steves, PhD, Rangsun Parnpai, PhD, Michael A. White, PhD, Jon D. Hennebold, PhD, Kyle E. Orwig, PhD, Calvin R. Simerly, PhD, Gerald Schatten, PhD, Charles A. Easley IV, PhD. Fertility and Sterility Science, published: September 07, 2021.)