Growing sperm stem cells in culture. To help combat male infertility, NICHD-supported researchers are studying spermatogonal stem cells (SSCs), precursors to mature sperm. In the past, researchers had difficulty studying SSCs because the cells were unable to grow or thrive in a laboratory setting. Recently, the scientists overcame these technical barriers and developed a culture medium that contained the precise combination of cellular growth factors needed for mouse SSCs to reproduce themselves outside of the body. The researchers then successfully transplanted the newly grown cells into infertile mice, enabling the animals to produce sperm and father offspring with the genetic traits of donor mice. This technique holds promise for future application in humans and has the potential to result in exciting new treatments for some types of infertility, such as in males who undergo chemotherapy. Moreover, successfully growing human SSCs in culture could provide a ready source of more versatile adult stem cells for future study and for replacing diseased or injured tissue in patients with spinal cord injury or disorders like Parkinson’s or heart disease.

Enzymes and motile sperm. Many married couples dream of having a baby when they are ready, but some are unable to fulfill that dream. A recent study of infertile men showed that more than 81 percent of the time their sperm did not reach the egg,[i] encouraging researchers to focus attention on sperm motility. Two separate teams of NICHD-supported researchers have identified enzymes that are critical for sperm movement. In one study, researchers found that the enzyme GAPDS plays a key role in sperm movement and contributes to a process within the cell that produces fuel for the cell. In another collaborative study, researchers joined forces to discover that sperm also need an enzyme called sAC to move. These findings may lead to new therapies to help couples plan the families they want. For example, developing therapies that can help to restore one or both of these enzymes may help infertile men become fathers. Conversely, by interfering with the function of sAC or GAPDS in fertile men, researchers may be able to design safe and reversible male contraceptives.

Preventing miscarriage. Infertility affects about 6.1 million women in the United States.[ii]   One potential cause of infertility and a primary cause of miscarriage is an error in meiosis, the complex process that halves the number of chromosomes in eggs and sperm to prepare for conception. Errors in meiosis can lead to the death of the affected egg or miscarriage of a resulting embryo that contains an incorrect number of chromosomes. Recently, a team of researchers confirmed the identity of a receptor on the egg, Gpr3, which ensures that the egg waits for the proper signal before it divides its chromosomes in preparation for meeting a sperm. If the egg is missing Gpr3 or unable to activate the Gpr3 receptor, it cannot receive the signal and starts splitting early. With this knowledge, there is now a firm base to discover the corresponding inhibitory signal from the surrounding granulosa cells, and how that signal is regulated by hormones throughout the menstrual cycle. Identifying Gpr3 adds another piece to the puzzle surrounding human reproduction and suggests new ways for treating female infertility and for preventing miscarriages.