How the sex of one fetus can affect its neighbors in the womb

ARI SHAPIRO, HOST:

A sibling can change your life, and sometimes that influence starts before birth. As part of our series on the science of siblings, NPR's Jon Hamilton explains how the sex of one fetus can affect its neighbors in the womb.

JON HAMILTON, BYLINE: It's called the intrauterine position phenomenon, and it was probably first described by cattle breeders in ancient Rome. Bryce Ryan is a professor of biology at the University of Redlands in California. He says the Romans noticed that something odd happens when cows have more than one calf at a time.

BRYCE RYAN: Occasionally, they'll give birth to twins. And if the twins are opposite sex, if one's male and one's female, the female is just about always sterile.

HAMILTON: These females, known as freemartins, also act more like males when they grow up. Scientists began to understand why in the early 1900s. Hormones from the male twin were affecting the female's development. Ryan says different versions of the phenomenon have been seen in rodents, pigs, sheep and probably humans.

RYAN: It's really kind of strange to think about something so random as who you develop next to in utero can absolutely change the trajectory of your development and therefore your physiology for your entire life.

HAMILTON: Ryan says the intrauterine position phenomenon works like this when males and females share a womb.

RYAN: If you're male, you have testes, and you produce a lot of testosterone and you become a male. If you're a female, you have ovaries, and at least early in development, you don't actually produce very much of anything.

HAMILTON: But when both sexes are present, there can be some hormonal crosstalk. Ryan says that's especially true in rodents, which can carry litters with more than a dozen pups.

RYAN: Those fetuses are packed so tightly together in the uterus, the testosterone can travel from pup to pup, and it can also be carried by the circulatory system.

HAMILTON: Especially when a female is squeezed between two males. These females can still reproduce, but their genitals develop in a slightly different way, and they tend to be more aggressive. Usually, those subtle changes only matter to lab scientists, but Ryan says they became part of a public debate in the early 2000s thanks to a plastic additive called BPA.

RYAN: For a lot of people, this was a wake-up call, maybe the first wake-up call that plastics were not universally good.

HAMILTON: BPA acts like a weak version of the hormone estrogen, and studies showed that small amounts were leaching out of some plastics and into people. At one time, scientists might have assumed these exposures were harmless, but research on intrauterine position had shown that even a trace amount of a hormone could affect a developing fetus. So BPA became a lightning rod for concern about hormone-like chemicals. In 2009, pediatrician Alan Greene spoke at a rally to ban BPA in products for young children in California.

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ALAN GREENE: Knowing what we know today, as a physician, as a father, I would never on purpose expose my own children to BPA. I would not do it.

HAMILTON: The plastics industry offered a different message.

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UNIDENTIFIED PERSON: BPA is well tested, and we know from FDA scientists that the trace amounts we are exposed to from materials that keep our food safe are safe for us.

HAMILTON: Scientists were and are divided on the safety of BPA. One reason involves intrauterine position. Ryan says early on, a study showed that the phenomenon could affect the very experiments used to assess the safety of BPA, also known as bisphenol A.

RYAN: Female mice developing in between two other females were more sensitive to bisphenol A than a female that was developing between two males.

HAMILTON: And if hormones from a sibling could negate an experiment, so might lots of other subtle factors. Scientists are still trying to understand those factors. They are also trying to figure out whether the intrauterine position phenomenon exists in people. Ryan suspects that it does.

RYAN: There have been some studies that have shown that opposite-sex twins, especially the females, do show some differences in behavior and may also show differences in physiology as well.

HAMILTON: Differences like how many children they have, how their facial features develop and how their brains process language. But it's hard to know for sure because it's really difficult to study a species that lives in the world, not a lab.

Jon Hamilton, NPR News.

SHAPIRO: And for more stories in this series, visit npr.org/siblings. Transcript provided by NPR, Copyright NPR.