A team of scientists has overcome several barriers and successfully grown functioning sperm cells in a recent experiment.1 While the researchers still have much more work to do before they can test their technique in men, they are hopeful that this is a first step in a possible new treatment for male-factor infertility.
"This advance opens up an exciting range of possibilities for future research, from developing new treatments for male infertility to enhancing the survival of endangered species," said Duane Alexander, MD, director of the National Institute of Child Health and Human Development at the NIH, which partly funded this study.
Growing Viable Sperm Cells
For their research, Hiroshi Kubota, DVM, PhD, a research assistant professor of Cell Biology at the University of Pennsylvania and his colleagues successfully grew sperm stem cells, then transplanted them into infertile mice, which were subsequently able to produce sperm and father offspring genetically related to the donor mice.
Kubota's team successfully developed the right combination of conditions to allow the cells—known by their medical term as spermatogonial stem cells—to grow properly in vitro, or outside the body. The cells are incapable of fertilizing eggs, but give rise to cells that eventually develop into sperm.
Once the proper conditions for growing the precursor cells were established, "spermatogonial stem cells proliferated over 6 months, reconstituted long-term [sperm production] after transplantation into recipient testes, and restored fertility to infertile recipients," Kubota and his colleagues wrote.
A Decade of Research
This isn't a new approach for this group of scientists. More than a decade ago, the same research team developed a method to transplant sperm stem cells from one mouse into another.2 The mice receiving the stem cells then produced sperm—fully capable of fertilizing egg cells—that had the genetic characteristics of the donor mice.
The key difference between that study and the latest is that the team can now grow these stem cells in a culture dish before transplanting them. The ability to grow sperm stem cells in culture provides a ready source of cells that medical researchers can manipulate genetically, explained the study's senior researcher, Ralph Brinster, DVM, PhD, a professor of Reproductive Physiology. For example, scientists could theoretically implant a new gene into a spermatogonial stem cell, reproduce a large number of these cells in a culture dish, and then implant the cells into recipient animals, he said. With the new gene, the animals could then pass the new trait onto their offspring, which could be a great value to breeders.
Infertility Implications
But more importantly, this is an initial step toward an experimental infertility therapy. "It opens up a new chapter in fertility medicine," Brinster stated. Implanting a new gene into the stem cells before transplantation could potentially erase the genetic abnormality that caused a man's infertility, the researchers said.
"If each parent in a couple carries a similar defective recessive gene for a disease, for example, it should be possible in the future to harvest male spermatogenic stem cells, correct the gene in culture, and implant the stem cells back into the male to produce normal sperm," explained Brinster. "The couple could then conceive a healthy child."
Further, by manipulating the culture media that contains the stem cells, medical scientists might be able to induce the cells to develop into sperm cells that could be used to fertilize eggs, as they demonstrated with mice in this experiment.
Growing the cells in vitro indefinitely also allows for the possibility to create sperm with the goal of later implanting the cells in a male. That could be useful for correcting some types of infertility in which one or more testicles cannot naturally produce sperm.
There is another implication for cancer patients. Currently, men undergoing cancer therapy who want to protect their reproductive systems from the potential damage that such treatment can cause often choose to bank their sperm for later use. However, using the approach described in this study, sperm stem cells could be cultured indefinitely to increase their numbers, then frozen and re-implanted at a later date, restoring their fertility, the researchers theorized.
1. Kubota H, Avarbock MR, Brinster RL. Growth factors essential for self-renewal and expansion of mouse spermatogonial stem cells. Proc Natl Acad Sci USA 2004 Nov 23;101(47):16489-94. Epub 2004 Nov 23.
2. Brinster RL, Avarbock MR. Germline transmission of donor haplotype following spermatogonial transplantation. Proc Natl Acad Sci USA 1994 Nov 22;91(24):11303-7.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
