Regardless of sex, we all start off in the womb with a genital tubercle – a teeny ambiguous nubble – between our legs. Then, around week 9 of gestation, this tiny structure turns into a penis or a clitoris depending on the different hormones we come across.
A new study, published in the open-access journal PLOS Biology, has further unraveled the mysteries of penis formation in the womb and the roles of different hormones involved. It turns out, it’s not quite as simple as scientists previously assumed.
One of the main “ingredients” needed for penis development in the womb is testosterone, a hormone found that's responsible for many of the physical characteristics specific to adult males, although it is also produced by women in smaller doses. As a fetus, the testes pump out this hormone, which is then converted into 5α-dihydrotestosterone (DHT), to prompt the genital tubercle to develop into a penis not a clitoris.
However, just testosterone and the testes are not enough to seal the deal. This new research showed that penis development also relies on a second process, called the "backdoor" pathway, which results in androsterone being converted into DHT as well, without the need for testosterone from the testes. Strangely enough, the enzymes needed for this pathway were found in the liver, the adrenal gland, and placenta. This suggests that the male genital tubercle can convert both testosterone and androsterone into DHT.
“Our results demonstrate that masculinization of the male fetus depends not only on the testes, but also on other tissues, especially the placenta," Paul Fowler of the University of Aberdeen and Michelle Bellingham of the University of Glasgow in Scotland, said in a statement. "They also suggest an explanation for why disorders of placental insufficiency can lead to hypospadias and other abnormalities of growth of the male external genitalia."
To reach these new insights, the team drew blood samples from 42 male fetuses and 16 female fetuses between 11 and 21 weeks of pregnancy. During the gestation, they then tracked levels of the various hormones and noted how genes were expressed in tissues.
They hope that a better understanding of this process could help prevent common birth defects that can affect the genitals. Writing about their research for The Conversation, Fowler and Bellingham explain that recent decades have seen a massive rise in cases of hypospadias, a disorder affecting the development of the urethra. This increase has been attributed to the contaminants from plastics, such as phthalates, that are known to meddle with the work of hormones. Hopefully, if researchers have more knowledge about the hormonal pathways of genital development, it could be used to prevent such disorders.