Twin fates: sharing the womb with a brother may influence a girl's development

Science News, May 10, 2008 by Deborah Blum

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KELLY KLUMP IS A CURLY-HAIRED, COMPACT WOMAN WHO IS FASCINATED BY EATING disorders. Her own habits are healthy, but as a high school "peer counselor" she found herself besieged by girls struggling with the addictive starvation of anorexia nervosa and the compulsive binge-and-purge of bulimia. Now a 37-year-old associate professor at Michigan State University in East Lansing, Klump has spent the past 10 years probing the genetic influences in such illnesses and pondering a stubborn question about why biology makes women more likely targets than men for eating disorders.

Lately she has revisited that frustrating question from a new angle. Working with graduate student Kristen Culbert and other colleagues, Klump published a paper in the March Archives of General Psychiatry focusing on a very specific group: females from a male-female twin pair.

A few years ago this would have seemed a rather narrow approach to a widespread problem. But several recent studies now suggest that the girl twin in a mixed pair offers provocative evidence concerning the way biology shapes people before birth.

Psychologists in both the United States and Europe have found that females from opposite-sex twin pairs tend to be more aggressive and adventurous, process spatial information more like men, and show more typically masculine left brain dominance during language tests. Across a range of research, these female co-twins seemed shifted toward the male end of the behavioral spectrum.

Such studies prompted Klump and Culbert to test a specific hypothesis: that girls with boy twins would also behave more like boys when it came to eating disorders. In other words, these girls' risk would drop. Using an eating behavior survey, questioning several hundred twin-pairs from the Michigan twin registry, and looking at opposite-sex and same-sex, both male and female twins, the scientists found their prediction was absolutely on.

Their female co-twins had a lower level of eating disorders, tending toward the male range. By contrast, the same-sex female twins had the highest level of all the twin sets questioned. The Michigan State scientists suspect that the reason can be found in the prenatal environment: Sharing the space with a developing male can apparently alter female development in some small but interesting ways.

"Opposite-sex twins have not historically been a target for biological research," says Dennis McFadden, a psychology professor at the University of Texas at Austin, who has been studying male-pattern hearing in female co-twins. "For a long time, people just thought that all the learning could be done in same-sex twins. So until recently they've been grossly understudied. And now, all at once, there's awareness of this tantalizing potential."

Testosterone tsunami

DEVELOPMENTAL BIOLOGISTS HAVE LONG KNOWN THAT EXPOSURE to hormones during gestation has a potent effect on fetal development, especially for males. Near the end of the first trimester of human pregnancy, at about 10 to 12 weeks, male fetuses begin producing a remarkable blast of the steroid hormone testosterone, "something like adult levels," says psychology professor and primate researcher Kim Wallen of Emory University in Atlanta. A similar process exists for most mammals: The timing and the amount of androgens such as testosterone before birth are essential to normal male development.

Human fetuses begin life in a sex-neutral body, whether carrying the XX chromosome match that signals a tiny female or the XY pairing that means a male. But there's another factor in play: Female is considered the "default" state for human development; without that extra testosterone, the body simply continues toward a female design. If XY males don't get enough prenatal androgens, as happens with some genetic defects, those males develop looking like well-formed females.

The female fetuses, on the other hand, don't need to crank up estrogen to turn into a girl. In fact, they tend to produce the hormone at mere trace levels throughout gestation. So, starting in the late 1970s, scientists began to wonder whether exposure to a brother's testosterone before birth might affect the sister's development.

Biologists studying mice turned up the first indications that this was a real possibility. Like humans, male mouse fetuses produce a critical testosterone boost, about midway through gestation. Unlike humans, mice routinely produce large mixed-sex litters. In fact, during their mother's pregnancy, the fetal mice are packed in place, almost as neatly as a line of peas in a pod. The researchers discovered that for developing females, the sex of their pod-neighbor made a real difference.

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Females who were surrounded by other females in utero (sometimes called 0M for their zero-male exposure) developed in the standard way. So mostly did those between a male and another female (1M). But females who were placed between two males (2M) could be identified, after birth, by their more male body proportions. Further experiments confirmed that the physical difference could be traced to a prenatal diffusion of testosterone (steroid hormones slip fairly easily through cell membranes). In fact, as zoologist John Vandenbergh wrote, "the more males in proximity to a given female, the more masculine characteristics the female displays."