Boys and girls differ in genetic response to what mom eats

Placentas of female fetuses more sensitive to maternal diet

You are what your mother ate, to some extent; how much depends partly on whether you are a boy or a girl, new research shows.

A study in mice reveals that expectant mothers’ diets influence gene activity differently in the placentas of male and female offspring, researchers report online March 8 in the Proceedings of the National Academy of Sciences. The placentas of female fetuses proved most sensitive to maternal diet, producing more of a protein that responds to estrogen, say researchers led by Cheryl Rosenfeld, a reproductive biologist at the University of Missouri in Columbia. The extra sensitivity could make female offspring more susceptible to estrogen-mimicking chemicals in the environment.

“The idea that maternal diet is affecting placental proteins is a neat observation,” says Retha Newbold, an emeritus reproductive and developmental biologist with the National Institute of Environmental Health Sciences in Research Triangle Park, N.C. “But the idea that it affects male and female placentas differently is really nice.”

Sex differences in response to maternal diets showed up even before fetuses developed sex organs or began producing hormones such as testosterone or estrogen, the researchers found.

Such early signs of a boy-girl split in response to mom’s diet “implies that many of the sex differences are conferred by the placenta itself, and that’s really novel,” says Staci Bilbo, a developmental neuroimmunologist at Duke University in Durham, N.C.

Rosenfeld and her colleagues began studying sex differences in the placenta to help solve a mystery about why maternal diets can skew sex ratios of offspring and lead to health differences later in life. Previous research had shown that moms who eat low-calorie diets before and during pregnancy tend to have more female offspring. High-calorie diets favor males, and sons of obese moms are more likely to be obese and suffer from metabolic diseases such as diabetes than are their sisters.

The researchers thought that examining placentas might show reasons for those sex differences. “If the placenta doesn’t fare well, the fetus isn’t going to fare well,” Rosenfeld says.

Her team put would-be mothers on one of three diets before and during pregnancy — a very high-fat diet, regular mouse chow, or a low-fat diet. Each diet produced its own characteristic pattern of gene activity in the placentas of fetuses examined about mid-way through gestation. The dietary differences were mostly expected, but the researchers were surprised to find that, in each case, female placentas reacted more strongly to the diets than male placentas did. A total of 700 genes showed sex differences in activity among the diets, with 651 of those genes more active in female than male placentas.

A gene encoding the estrogen receptor alpha protein was more active in placentas of female fetuses whose mothers were on the regular chow diet, while moms on the very high-fat diet had female offspring with increased levels of androgen receptors in their placentas. These differences in gene activity could make female fetuses more vulnerable to the effects of endocrine disruptors — chemicals that interfere with hormones — than male fetuses are, the team speculates.

The researchers still can’t say how maternal diet affects sex ratio, because at the stage of pregnancy they examined the proportion of males to females was already skewed.

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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