We owe a lot to our moms—and if you happen to have a penis, there’s now yet another reason to phone home on Mother’s Day.
According to a study published today in the journal PLoS Biology, a human mother’s placenta may help cue a growing fetus into sprouting biologically male genitalia. The new research both highlights a previously underappreciated role for maternal hormones in the formation of this oblong appendage, and could help explain why problems with the placenta are often associated with genital malformations.
“In many respects, this is quite a game changer,” says Richard Sharpe, a developmental biologist at the University of Edinburgh in the UK who was not involved in the study. “Traditionally, we think very much along the lines of, ‘Whatever gonads the fetus has will determine [the biological sex it appears to be].’ But the placenta is absolutely key.”
In the early days of pregnancy, fetal genitalia look pretty ambiguous, with not much more than amorphous ridge in place. Around the eighth week of development, a subtle metamorphosis begins, nudging the growing infant onto a trajectory that will yield, in the case of males, a penis. But while scientists have long known that a specific cocktail of chemicals is required to trigger these changes, many details about the path to phallic formation remain elusive.
The standard formula is this: During development, the burgeoning testes release a steady stream of testosterone, which travels to the genital ridge. There, testosterone is converted into a more potent hormone called DHT, which then sends out marching orders to direct the formation of a penis instead of a clitoris. In most mammals, testosterone is enough to trigger this change; not so for humans. Even if the testes are fully functional, some babies are born with disorders of sex development, or ambiguous genitals—which told scientists that, to properly build the penile architecture during development, there had to be at least one other necessary ingredient.
To pinpoint that piece of the penis puzzle, team of researchers led by Paul Fowler, a reproductive biologist at the University of Aberdeen in the UK, measured fetal hormone levels during the second trimester, when the genitals are deep in the throes of transformation.
By comparing hormone levels between male and female fetuses, the researchers uncovered two hormones that are more abundant in penis-bearing babies. One of the two, just run-of-the-mill testosterone, was hardly news. The other, androsterone, seemed to be that crucial missing link—but the story with this hormone was a bit more complex.
Like testosterone, androsterone can serve as raw material for DHT production. Although the testes specialize in pumping out gobs of testosterone, in these organs, there’s almost no androsterone to be found.
This meant the lion’s share of the androsterone was likely being manufactured elsewhere. And when the scientists searched through other fetal tissues for the hormone, several stood out, including the fetuses’ adrenal glands (the hormone factories that rest atop the kidneys). But that wasn’t the only place androsterone seemed to hail from: It also appeared to come directly from the mother’s placenta.
In other words, through this hormonal wellspring, moms were essentially kindling the growth and development of their sons’ penises.
“We’ve always known that placental function is key to normal fetal development,” Sharpe says. “This adds to that and says there’s another dimension to it.”
And the direct transfer of androsterone seemed to be only part of the story. One of the main ways in which androsterone is made is through chemical modifications to progesterone—a hormonal mainstay of the placenta. Fowler thinks this source of progesterone ends up trickling into the growing fetus, where organs like the liver catapult it on the path towards androsterone.
In this way, penile development is far from a testicular solo act; rather, it’s a team effort, bringing multiple tissues together in pursuit of a common goal. “We tend to think about different organ systems as separate, but in fetal development especially, they’re all speaking to each other,” Fowler says. And an idea like that may be poised to rewrite the penis development playbook.
“We were thinking too simple [with the] the canonical pathway [of just testosterone],” says Christa Flück, an endocrinologist and developmental biologist at the University of Bern in Switzerland who was not involved in the study. “Now we are finding all these new factors… We really don’t understand the whole story yet.”
The placenta’s contributions to genital development may also offer an explanation for other medical phenomena—like the link between placental abnormalities and disorders of sexual development in male infants, Fowler says. It may be the case that, in some instances, the flow of hormones from mother to baby is blocked. But that theory still needs testing.
Anna Lauber-Biason, an endocrinologist and developmental biologist at the University of Fribourg in Switzerland who was not involved in the study, also praised the work for its “exciting” results. However, she notes that an important follow-up will be figuring out if the placenta also bequeaths hormonal heirlooms to daughters.
“What I would like to see next is what happens with the girls—we are always forgotten somehow,” she says. It’s slightly in jest—but in fact, studies of male genitalia and genital development dominate the literature on reproductive biology, ultimately overshadowing female-focused studies. Researchers have argued that this bias paints an incomplete portrait of the intricate dynamics of sexual evolution.
“We are both equally important,” Lauber-Biason says. “The researchers should follow up and let us know what happens.”
Fowler and his team plan to do exactly that. But in the meantime, he says, there’s something also to be said for how similar the two typical biological sexes are.
“There is a considerable amount of overlap [in hormone levels] between males and females,” Fowler says. “I think it would be beneficial to get away from this idea that men are full of testosterone and women are full of estrogen. In fetal life, that’s not true… and that’s when your foundations are laid.”