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Stanford Researchers One Step Closer To Developing Synthetic Sperm And Eggs

In a development that is certain to spark hope, concern and outrage, scientists from Stanford University have been successful in creating primitive artifical human sperm and eggs from embryonic stem cells. The study, published in the online journal of Nature, found [1]:

Researchers at Stanford University, which harvested the stem cells from an embryo, claim the breakthrough could eventually cure infertility in men, birth defects and even extend the menopause in women.

Previous studies have claimed to have reproduced egg and sperm cells in the laboratory but they were always slightly damaged or malformed. The researchers in the latest study believe their germ cells – the cells that eventually turn into sperm and eggs – are so perfect it would be possible to grow them into fully functioning reproductive cells.

The scientists, who published their findings in Nature, claim to have unlocked the genetic “recipe” that leads to these unique cells being formed.

They used human embryonic stem cells from excess IVF embryos and treated them with proteins to stimulate the growth of germ cells.

Some fertility specialists have already weighed in [2]on the import of this research:

“This research basically tells us how to make a gamete,” said Dr. Raymond Anchan, a fertility specialist and stem cell researcher at Brigham and Women’s Hospital in Boston. “If we understand this, then we can think about making gametes from patient-specific stem cells,” said Anchan, who was not involved in the study.

According to the National Women’s Health Information Center, infertility affects approximately 10 percent of U.S. women — some 6.1 million women aged 15 to 44. For many of those individuals, and also for many men, infertility stems from low or abnormal gamete production. Though researchers have had sporadic success turning human ESCs into germ cells, the process has been inefficient and difficult to study in the laboratory. Reijo Pera decided to try to change that.

The Stanford team knew that feeding human ESCs growth factors, called bone morphogenetic proteins, would induce the cells to differentiate into germ cells. Led by postdoctoral fellow Kehkooi Kee, they developed a “reporter gene” system to tag and identify the cells they wanted — those that were differentiating into germ cells — by making them glow fluorescent. That fluorescence would then enable the team to count developing germ cells, and also purify them.

Using various methods, the team determined that the fluorescent cells tagged by Kee’s reporter system were so-called “primordial” germ cells. Accounting for just 5 percent of the cell population in this study overall, these cells are basically early, immature germ cells.

Experimental system in hand, the team then turned to the role of the DAZ protein family in the production of these very early cells. DAZ proteins were already known to be associated with male infertility; that’s how Reijo Pera first identified them in the 1990s. The question was: How exactly do they affect germ cell development?

By alternatively blocking and boosting the expression of the DAZ family members DAZ, DAZL and BOULE, and counting the cells that emerged, the team determined that DAZL is required for differentiation in primordial germ cells, while DAZ and BOULE push the cells further towards the production of true gametes. Importantly, by overexpressing all three proteins, the team produced cells with the same genetic content as gametes.

“We didn’t know these genes are major players in germ cell development,” said Reijo Pera. “We suspected it, but here we can directly show that we get differences in the pathway. For a biologist, that’s incredibly exciting.”

Reijo Pera said the system can now help researchers map germ cell development and identify factors that can enhance or inhibit that process. Longer term, her team wants to coax germ cells to differentiate from adult, non-embryonic stem cells — using cells such as skin cells that are manipulated to regress to an embryo-like state.

The implications of this development cannot be understated. Nor can the debate that will inevitably ensue. Just as an example, theoretically it will be possible to use male DNA to create an oocyte. In such an instance, a same-sex couple could ultimately produce a child genetically related to both fathers.

As remarkable as these findings are, the science is still at least 5 years away. Beyond that many legal hurdles will likely arise as use of artificial gametes have been prohibited in many countries around the world. As the science develops, there will be much debate regarding the ethical, philosophical, emotional and safety concerns of using artificial sperm and eggs.