The Sciences

Scientists create sperm-producing female fish by turning off a single gene

Science SushiBy Christie WilcoxJun 12, 2015 5:00 PM

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As far as natural selection is concerned, sex is just about everything. All activities a creature engages in are in service of reproduction. Not surprisingly, the nitty gritty cellular details of reproductive biology are thus of extreme interest to many scientists. Biologically speaking, males are the members of a species that generate sperm while females produce eggs. But now, scientists from Japan have shown that a female fish can produce fully-functioning sperm—and would all the time, if it weren't for the expression of a single gene. Offspring from sexually reproducing species begin when two reproductive cells, called gametes, from their parents fuse. But not all gametes are the same; for reasons that still remain somewhat of a mystery, one parent donates a much larger gamete, the egg, while the other donates only essential genetic material in the form of sperm. Sperm are cheap — as they consist of little more than DNA packed in a swimming case, they are produced by males in unfathomably large numbers while females pour several thousand times more energy into producing their fewer, precious eggs. Understanding the underlying differences between egg and sperm production can help scientists learn more about the evolution of sex itself, as well as potential ways to treat medical conditions such as infertility. A team of scientists based at the Laboratory of Molecular Genetics for Reproduction at the National Institute for Basic Biology in Okazaki, Japan, were studying the reproductive biology of a small minnow-y fish called the medaka (Oryzias latipes), a member of the ricefishes. They identified a gene which was active in the egg cells but not in the surrounding ovary tissues — foxl3 — and sought to determine its purpose by creating knockout fish lineage that lacks expression of that gene. To their surprise, when foxl3 was supressed, the otherwise female fish started mostly producing sperm instead of eggs. But even more strangely, these female fish with no foxl3 expression began producing sperm only a week after hatching, a whole three weeks earlier than their wild male counterparts. The sperm themselves were perfectly functional — when the team used these female-made sperm to artificially inseminate eggs from wild-type female fish, they worked just fine, and most of those fertilized eggs hatched into living, healthy baby fish. The knockout males were seemingly unaffected by the loss of foxl3. Their results, published this week in Science, suggests that, at least in the medaka, a single gene suppresses 'maleness' in developing reproductive cells. These data are in stark contrast to previous research in mammals, as they suggest that the 'default' track for gametes is to become sperm rather than eggs.

A Female medaka lacking foxl3 genes, looking very much like a normal female medaka — but her ovaries (lower images) tell a different story. In them are lots of sperm alongside a handful of eggs. Image provided by the National Institute for Basic Biology However, this isn't the first time a foxl gene implicated in maintaining femaleness. Back in 2009, scientists found that female mice will produce testes instead of ovaries, even as adults, if the gene foxl2 is knocked out. But in that case, the entire reproductive organ changed from female to male. These fish are able to develop healthy male gametes inside a very female ovary. "In spite of the environment surrounding the germ cells being female, the fact that functional sperm has been made surprised me greatly. That this sexual switch present in the germ cells is independent of the body's sex is an entirely new finding" first author Toshiya Nishimura told Reuters. Future research may investigate similar genes in mammals to see if we, too, have a sperm-suppressing gene that ensures our egg cells stay on track. For now, though, the team is continuing their study of foxl3 in fish to discover how exactly it works. They're interested in determining what regulates its expression as well as what the gene product actually does to prevent gametes from becoming sperm. Citation: Toshiya NishimuraTetsuya SatoYasuhiro YamamotoIkuko WatakabeYasuyuki OhkawaMikita SuyamaSatoru Kobayashiand

Minoru Tanaka (2015). foxl3 is a germ cell-intrinsic factor involved in sperm-egg fate decision in medaka. 

Science

DOI:10.1126/science.aaa2657

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