Microbiology/Genetics

New Hope for Hermaphrodites

More findings on the genetics and phisiology of the sex development

By Stefan Anitei, Science Editor

25th of July 2007, 18:36 GMT

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There are increasingly more cases in which the inner sexual feelings do not march the external sex. And it's not merely about homosexuals. There are also numerous cases of ambiguous genitalia in humans, about 1: 4500 births.

"It is usually the first question new parents are asked - is it a boy or a girl? But when it is not possible to determine a baby's sex it is upsetting for families and raises questions about whether to assign a gender immediately or wait until a child gets older. These conditions are common, almost always traumatic for the families involved and require significant healthcare resources through

corrective surgery, hormone therapy, psychological support and other related treatments." said Professor Peter Koopman, from University of Queensland's Institute for Molecular Bioscience (IMB), who has recently received the GlaxoSmithKline Australia Award for Research Excellence that offers hope to children born with sexually ambiguous genitalia and other sexual development issues.

In 1990, Cambridge's Peter Goodfellow found SRY, a gene located on the Y chromosome responsible for triggering the male development. Any mutation on it was found to induce female development. When researchers inserted SRY into a XX female fetus mouse, the offspring was born male.

Following the discovery of SRY, Koopman has been working to understand the complex developmental networks within the gonads that trigger cells to turn into sperm or eggs. When these signals go out of control, it appears that testicular cancer develops.

"My work is essentially a study of how testes or ovaries develop in the embryo. The genetic controls that underpin development are complex and the pathway often breaks down, which can result in a broad spectrum of intersex conditions including a child of uncertain sex," said Koopman.

Tracking down the genes involved in this process and assessing how they work is crucial in understanding the emergence of these sexual abnormalities. Koopman's team is searching for other genes important for male/female sex determination and testis/ovaries development.

"A major motivator for me is to be involved in work that makes a real difference to people's lives. Research is a painstaking process but the belief that my work will benefit people is what keeps me so passionate about it."

It is increasingly clear that human sex is not determined by sex chromosomes (X and Y) but by genes placed on those chromosomes. A team led by Eric Vilain, a geneticist at the University of California, Los Angeles, showed that SRY does not trigger male development directly, but by blocking an "antitestis" gene. In fact, males with SRY but XX chromosomes range in traits from normal males to an ambiguous mix.

Test-tube investigations showed that SRY can stop gene transcription, working through interference. In 1994, Vilain's team succeeded in genetically modifying a male mouse while the gene was missing.

It appears that sex develops due to a fragile balance between about (till now discovered) 50 promale, antimale, and profemale genes, like DAX1 or WNT 4 (on the X chromosome). Over-expression of DAX1 develops an XY individual into a female. Vilain's team and Koopman's are collaborating to investigate expression patterns of the sex-specific genes in transsexual people.

TAGS:

hermaphrodite | sex | gene | testicle | ovaries

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