How gender is determined in the brain

During prenatal development, the brains of most animals, including humans, develop specifically male or female characteristics. New research sheds light on how this process is triggered.

In the study, published in the journal Nature Neuroscience, Margaret McCarthy from the University of Maryland and colleagues studied brain development in newborn rats.

She found that giving estradiol, a testosterone derivative, triggers a mechanism by which certain genes in the brain are "unsilenced", allowing them to initiate the process of masculinisation.

This process involves a group of enzymes known as DNA methyltransferases, or Dnmts, which modify DNA to repress gene expression.

"This gives us a new understanding of how gender is determined in the brain," said McCarthy.

The researchers also found that by inhibiting Dnmts, they could alter the reproductive behaviour of male and female mice. Researchers injected Dnmts inhibitors into a specific region of the female brains, a region known as the preoptic area, or POA.

In every species that's been studied, including humans, the POA plays a key role in governing male sexual behaviour.

The injections occurred after the first week of birth, the time when the window for brain sexual differentiation was thought to have been closed.

Despite this, the preoptic area in these animals was transformed, and took on structural characteristics of a male rat.

The female rats also behaved differently, displaying sexual behaviour typical of male rats.

In another experiment, they genetically deleted the Dnmts gene in female mice. These animals also showed male behaviour patterns.

"Physically, these animals were females, but in their reproductive behaviour, they were males. It was fascinating to see this transformation," said co-researcher Bridget Nugent.