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Brain ‘Gender’ Is More Fluid Than Originally Thought, Research Reveals

FIONA MACDONALD
9 APR 2015

For the first time, researchers in the US have managed to flip the gender of the brains of newborn rats, causing physically female rodents to behave like males. The research suggests that neurological sex is more flexible than once thought.

 

"Nobody has ever shown that this is how the process works," said Margaret McCarthy, co-leader of the research from the University of Maryland, in a press release. "This gives us a new understanding of how gender is determined in the brain."

The brains of most animals, including humans, develop specific male or female characteristics during prenatal development, and it was traditionally thought that within a few days of birth, the brain's gender was set in stone. But the new research, which has been published in Nature Neuroscience, suggests that this isn't the case at all.

To work this out, the team injected 10-day-old female mice with a substance that acts like estradiol, a steroid that surges during the development of male rats, and is used in humans to help treat menopause symptoms. Estradiol works by inhibiting DNA methyltransferase (Dnmt), an enzyme that usually silences certain genes. By blocking the action of Dnmt, these genes were 'unsilenced' and able to trigger the masculinsation process - even after the 'window' of sexual differentiation had closed. 

"Physically, these animals were females, but in their reproductive behaviour, they were males," said one of the researchers, Bridget Nugent, who is now at the University of Pennsylvania. "It was fascinating to see this transformation."

Not only did their behaviour change dramatically, but the rats' brains also structurally transformed. 

In a follow-up experiment, the team deleted the Dnmt gene in female mice, and found that their brains also became male. This is one of the first studies to help unravel the mysterious process of sex differentiation in the brain, and shows that continual Dnmt exposure is necessary throughout development to ensure that a brain turns female.

"It was thought that once established, sexual differentiation could not be undone," Nugent told PBS. "Our work shows that sex differences in brain and behaviour are epigenetically regulated, meaning that sex differences are not hardwired in our DNA but programmed during development."