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mission between animals; it might also be spread as an aerosol or by direct contact between animals, he suggests. Scientists are also puzzled by the viruss ability to infect the fetus without killing it. It is unusual that a pathogen that kills mammalian cells in the petri dish can stay in an organism as sensitive as a fetus for such a long time without causing an abortion, Beer says. He suggests that this trait might be the viruss way of surviving the
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winter, when no insects are around. With biting midges expected to take off again in May or sooner, animal health experts are preparing for the next season of Schmallenberg infection. Preliminary data from two cows show that the animals that had been infected earlier are immune to the virus. But of course we dont know whether this goes for all cows or how long this protection will last, Mettenleiter says. Work is already under way on a vaccine.

At FLI, scientists are trying the classical approach: inactivating the virus chemically and adding an adjuvant. Although the vaccine might be easy to produce, the rigorous testing demandsscientists have to be sure it is safe in pregnant animalswill probably take a long time. Its very unlikely that this will be ready this year, Mettenleiter says. But it might be ready in 2013.
Kai Kupferschmidt is a science writer in Berlin.

KAI KUPFERSCHMIDT

Since 2004, reproductive biologist Jonathan Tilly of Massachusetts General Hospital in Boston has fought a relatively lonely battle to overturn one of the central dogmas of his eld. Men typically produce working sperm as long as they live, but most textbooks say female mammals are born with all the egg cells, or oocytes, they will ever have. Tilly has challenged that conventional wisdom, arguing that in miceand perhaps also in humansthere must be an ongoing source of new eggs. The proposal, its safe to say, hasnt been warmly received by fellow reproductive biologists. And Tilly didnt help his case in 2005 when he proposed that bone marrow was a source of eggs in mice. (That idea was discredited a year later.) But this week online in Nature Medicine, Tilly and colleagues report isolating rare cells in ovarian tissue from adult women that can grow in lab dishes and form immature oocytes. This latest claim is earning some cautious acceptance. As an egg biologist, Im juiced about this, says David Albertini of the University of Kansas Medical Center in Kansas City. The potential egg stem cells could provide a lab-based model for understanding how oocytes develop. And they may help scientists devise new ways to rescue the fertility of women who undergo cancer treatments or who suffer from premature menopause. Tillys battle to win over colleagues is far from over, however. There is no evidence that these cells actually exist in vivo, says Jock Findlay, a reproductive biologist at Prince Henrys Institute of Medical Research in Clayton, Australia. Since the 1950s, reproductive biologists have thought that egg precursor cells stop dividing about halfway through mammalian fetal development, giving a newborn female a nite number of potential eggs. A

baby girl, for example, is born with an estimated 1 million oocytes. By puberty, that number has declined to roughly 400,000. During a womans fertile years, follicles, the structures that host an oocyte and help it to mature, are activated at a rate of about 1000 per menstrual cycle. (Typically, only one mature egg is released into the fallopian tubes each cycle.) And once the oocyte supply runs low, menopause begins.

Green egg. A human oocyte derived from oogonial stem cells expressing green uorescent protein.

In 2004, Tilly and his colleagues published data in Nature that indicated that in mice, too many oocytes die during each menstrual cycle to sustain the supply of eggs for the animals lifetime fertility. New eggs, presumably from an unidentied stem cell, must be coming from somewhere, they proposed (Science, 12 March 2004, p. 1593). Other researchers dismissed that conclusion, saying the team had drastically
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overestimated the rate of oocyte death. Tilly persevered and in 2005, based on bone marrowtransplant experiments in mice, he and colleagues proposed in Cell that new oocytes might come from the marrow and travel to the ovary via the bloodstream. A paper in Nature quickly discredited that idea (Science, 16 June 2006, p. 1583). In 2009, however, Tillys original idea got a boost when reproductive biologist Ji Wu and his colleagues at Shanghai Jiao Tong University in China reported in Nature Cell Biology that they had isolated female germline stem cells from adult mouse ovaries. To prove their case, the team genetically modied the putative stem cells so that they produced green uorescent protein (GFP) and then injected them into the ovaries of sterilized mice. Those females gave birth to green-glowing pups, demonstrating that the injected cells had given rise to mature oocytes (Science, 17 April 2009, p. 320). It was still not clear, however, whether normal fertility and reproduction depend on such cellsor whether they exist in humans. And initial attempts by other labs to nd the mouse cells failed. Tilly says he, too, was frustrated at rst. I put a person on the protocol the day the paper was published. It took 10 months to get it to work. I still dont know why, he says. In the new paper, Tilly and his colleagues report that they have refined Wus cellcollection methods to isolate a more pure cell population from mouse ovaries. And they further describe shing out similar cells from human ovary tissue that Yasushi Takai, who works at the Saitama Medical Center in Japan, had previously collected from six women who had sex-reassignment surgery. The women were healthy and youngbetween 22 and 33 years oldand all agreed to have their frozen tissue used for the project.

CREDIT: VINCENT CENTER FOR REPRODUCTIVE BIOLOGY, MASSACHUSETTS GENERAL HOSPITAL

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Potential Egg Stem Cells Reignite Debate

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The cells, which Tilly calls oogonial stem cells (OSCs), are very rareonly about 1 out of 10,000 ovarian cells. The OSCs grow quickly in the lab, and they spontaneously form cells that visually and molecularly resemble immature oocytes. To nd out how the cells would behave in an ovary, the scientists injected OSCs engineered to make GFP into a piece of donated human ovarian tissue and then implanted the tissue under the skin of a mouse. When they looked at the grafts 1 and 2 weeks later, they found immature follicles with green oocytes at their center. Finding a human version of the cells Wu isolated is very exciting, says Evelyn Telfer, who studies oocyte development at the University of Edinburgh in the United Kingdom. But she and Albertini note that the current experiments dont address what, if any, role the apparent stem cells play in normal ovaries. And Findlay says the cells might be an artifact of the purication or culture methods the team used. Even the green oocytes should be viewed with caution, as GFP-tagged cells can fuse with unrelated cells, says Renee Reijo-Pera, a reproductive biologist at Stanford University in Palo Alto, California. The oocyte-like cells that grew from the human OSCs were far too immature to try fertilizing them, Tilly notes. And attempting such an experiment would need special ethical oversight, he says. He and Telfer have plans to see whether her techniques for maturing oocytes in vitro work with OSCderived cells. Whether the stem cells themselves could be a source of fertile oocytes for in vitro fertilization attempts is doubtful, Albertini says. He points out that expanding cells in culture almost always leads to accumulation of potentially harmful mutations. Still, Albertini says, studying the cells could help researchers. I think its a great model. It could help us move toward understanding how these incredible cells [oocytes] are born and how they develop. Tilly holds a patent on the OSCs, and he has started a biotech company to explore ways to use the cells to help improve fertility treatments. The company will screen for compounds that encourage the cells growth and development and will test whether compounds in the cells might be able to boost the fertility of aged eggs. But even Tilly admits that the controversy is unlikely to settle down anytime soon: Whether the cells represent what we believe they do? Thats going to take a while to weed through. GRETCHEN VOGEL
SCIENTIFIC CAREERS

Is Motherhood the Biggest Reason For Academias Gender Imbalance?

A new paper by two developmental psychologists on the dearth of women in academic science argues that the cause of the gender imbalance is much easier to identify than most researchers have posited. The solution is also more obvious, they say, although that doesnt mean it will be easy to implement (see sidebar). Not surprisingly, their provocative assertions, in a paper titled When Scientists Choose Motherhood, have stirred the pot in an already contentious eld. Writing in the March/April issue of American Scientist, Wendy Williams and Stephen Ceci of Cornell University argue ring to the typical time frame for an assistant professor to earn tenure at a major research university. Thats crazy. Men dont have to do that. Its this societal-designed unfairness thats rooted in biology. Researchers from nearly every scientic discipline have spent decades examining the reasons behind gender differences in math and science, from the nursery to the Nobel Prize. Some studies have found systemic bias and discrimination, whether deliberate or inadvertent, to be a major factor in the imbalance. Others argue that the slight edge for boys in mathematical ability among highly gifted students translates into a signif icant difference in adult success in mathintensive STEM elds. A third camp sees personal preferencesworking with people versus things, as some describe itas the driving force behind the divergent career choices by men and women. In their new article, Family matters. Cornell psychologists Stephen Ceci and Wendy Williams which builds on a 2011 with two of their three daughters. paper in the Proceedings of the National Academy of that the traditional view of female under- Sciences, the authors assert that a misdirecrepresentation as a complex mixture of dis- tion of resources toward problems that no crimination, differential abilities, and career longer exist has slowed progress. In particupreferences misses the mark. Instead, say the lar, they take issue with those who say that husband-and-wife team, the evidence from correcting the gender imbalance will require studies stretching back more than a decade a wholesale revamping of societal attipoints overwhelmingly to the primacy of tudes toward women and a reworking of the the dynamics of family formation in West- nations educational system. What is more ern society, or, in a word, motherhood. important, they say, is to change the curWilliams and Ceci are certainly not the rent rigid system at universities of rewardrst to note that the desire to have a fam- ing academic excellence. More exibility ily hives off a signicant fraction of women in the early years would allow them to have who have made it through graduate school a family and become full-edged researchand postdoctoral training in STEM (sci- ers, too, says Williams, who notes that havence, technology, engineering, and math- ing three daughters inuenced the couples ematics) elds and who stand at the brink decision in 2005 to jump into this contenof an academic career. Despite their clear tious eld. But the current system doesnt interest and talent, the authors say, women let them back in. in their prime childbearing years are often Its no surprise that an aggressive attack forced to make a stark choice between hav- on those analyses would trigger strong rebuting a family and pursuing a career for which tals from researchers who are passionate they have trained all their adult lives. Why about the topic. In particular, many researchis it that women are given one 7-year inter- ers think Williams and Ceci have oversimplival in which to amass a research portfolio ed what they say is a very complex issue and and have two kids? Williams asks, refer- selectively chosen data to bolster their case.
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