In this fully revised and updated edition of The Women’s Brain Book, neuroscientist Dr Sarah McKay delivers the essential guide to understanding women’s brain health and wellbeing, redefining how we think and talk about the female brain across the lifespan.

Read on for a fascinating extract from the book.

In Utero

What happens during the Great Sperm Race?

Armed with graph paper, a thermometer and a textbook understanding of the hormonal control of ovulation, I approached the business of trying to conceive with the earnest enthusiasm of a first-year PhD student. Fortunately, my body and husband cooperated, and in the blink of an eye, I’m now a mum to two gorgeous, extraordinary, very tall teenage boys.

When my oldest son was at primary school, it came time for my husband to take him to the requisite ‘Where did I come from?’ evening. I waited impatiently at home and when they arrived back (and despite my best attempt at cool, nonchalant parenting), my son had barely walked in the door when I asked, ‘So, where DO babies come from?’

‘Well, it’s weird and embarrassing. But interesting too,’ he said. ‘The sperms swim up the channel. Half go the wrong way and die. The other half go the right way and find the egg, which is releasing a chemical. One sperm locks in and is the winner!’

The moment the winning sperm ‘locks in’ to the egg and bequeaths either an X or Y chromosome is life-defining (and weird but interesting too). For most people, if you are biologically female, you inherited one X chromosome from your mother and one X from your father. If you are biologically male, you inherited one X chromosome from your mother and one Y from your father.

The two sex chromosomes get their names because they look like the letters ‘X’ and ‘Y’ under a microscope. Humans have 46 chromosomes – 23 from each parent – and each chromosome is made of a tightly coiled DNA double helix. Your complete DNA instruction manual contains surprisingly few genes – about 20,000 – of which one third contain the instructions for building the brain.24

The average neuron makes tens of thousands of connections, called synapses, with other neurons. And even being conservative, a brain of 86 billion neurons may contain as many as one hundred trillion synapses. If you’re savvy, you’ll realise that the maths doesn’t add up: there are far more synapses than there are genes to account for them.

It turns out the relationships between your genes, brain and behaviour are utterly complex. The DNA you inherited from your mother and father influences who you are, but not in a direct and simple way. In this book, I’ll share how those trillions of synapses in the female brain make us who we are. You’ll see that while genes provide the basic biological instructions for life, many other biological, social and psychological elements interact with, synergise and alter gene expression.

What’s the role of the placenta?

Strictly speaking, the fertilised egg is called a zygote. For the first six to seven days of its life, the zygote bumps and rolls down the fallopian tube, dividing multiple times until it becomes a hollow ball of cells, called a blastocyst. Once the blastocyst reaches the uterus, it embeds in the uterine wall, where cells keep dividing until the ball organises into two layers: one layer becomes the embryo and the other becomes the placenta.

The placenta is not merely an interface between a baby and mother. It acts as a giant gland releasing an assortment of hormones and chemical messengers crucial for maintaining pregnancy and preparing mum-to-be for birth. The placenta’s first job is to manufacture the pregnancy hormone, human Chorionic Gonadotropin (hCG). If you’ve ever anxiously waited for a thin blue line to appear after peeing on a pregnancy test, it’s an hCG chemical reaction you’re waiting for. hCG also triggers the cascade of hormones that stop your menstrual cycle.

Because the placenta derives from the same cells as the baby- to-be, either XX or XY, it too has a biological sex. Placental sex influences how the placenta works and how it buffers the baby against maternal stress, infection and diet. When excessive stress disrupts placental function, it can affect the baby’s brain development. The female placenta appears to be somewhat more protective compared to the male. This aligns with the strong sex bias observed in neurodevelopmental disorders, where boys are more likely to develop conditions such as autism spectrum disorder, ADHD and earlier-onset schizophrenia.

Why is neural tube closure so important?

By the time your pregnancy test is positive, or you skip a period (roughly two weeks after conception, or four weeks from your last period), your baby’s brain has begun to form. The nervous system is one of the earliest body systems to begin development and is one of the last to finish – brains continue to mature well into the third decade of life.

The human brain and spinal cord arise from the neural plate, which is a flattened layer of cells in the early embryo. Following a well-orchestrated sequence of steps, the flattened layer of cells folds, and the edges bend to touch in the middle, close over and ‘zipper up’ to form a neural tube. While looking at the early events in brain development might seem overly detailed, this phase is momentous because the entire central nervous system emerges from the neural tube.

You may have heard the term ‘neural tube’ spoken of before, usually in a very serious tone alongside the phrases ‘take your folic acid supplements’ and ‘birth defect’. Rightly so. The intricate and complex process of neural tube closure can go very wrong, and folate appears to play a protective role. Folate is the naturally occurring form of Vitamin B9 and is called folic acid when manufactured.

If the neural tube fails to close correctly by about 28 days after conception, a number of serious birth abnormalities can result, including spina bifida and anencephaly (literally meaning absence of brain). For all the evidence that folate prevents neural tube defects, the exact mechanisms by which the essential vitamin contributes to the zippering up of the neural tube is still not clear. As researchers state, the case of folate and the neural tube is ‘far from closed’.

What determines biological sex?

Until 10 weeks after conception, male and female embryos are indistinguishable. Although this is a book about the female brain, to understand female brain development, you also need to consider male embryonic development.

When XY embryos are six to eight weeks old, a gene on the Y chromosome called the ‘sex-determining region of the Y chromosome’, or SRY for short, activates. SRY is like a ‘master switch’ turning on genes that lead to testes formation in male embryos. Without SRY activation, ovaries develop instead.27

Jenny Graves, a professor of genetics at La Trobe University, notes that even though SRY is just one gene, the downstream effects of SRY – the development of testes that release testosterone – are profound. She explains: ‘Male hormones, such as testosterone, are synthesised by the embryonic testis and have far-flung effects all over the developing body. Androgens turn on hundreds (maybe thousands) of genes that determine male genitalia, male growth, hair, voice and elements of behaviour.’28 In the absence of a Y chromosome and the SRY gene, the default developmental option is for the fetus to become a female. ‘Default’ is a term some people find a little dismissive. To help unravel the complexities of prenatal brain development, I called Margaret McCarthy, a professor of neuroscience who studies the effects of hormones on brain development. ‘Default does not mean passive,’ she told me in a tone of voice that had me convinced she’s made that statement more than once. ‘Try saying, “The developing mammalian brain is destined for a female phenotype” instead,’ she suggested.

So, in short, embryos are destined to become female, unless the SRY gene in the Y chromosome turns on. Other genes are subsequently turned on and off to actively promote the ovarian development program and suppress the testes program.

How do sex hormones organise the prenatal brain?

Mother Nature is selfish. Her one and only goal is for us to have sex and make babies. To ensure dating and mating occur, the parts of the brain that control reproduction become ‘masculinised’ or ‘feminised’ to match male or female gonads. Sex hormones, especially oestrogen and testosterone, are crucial in ensuring the developing brain and gonads are in sync.

As McCarthy explained to me, there are two life phases when the brain is super-sensitive to sex hormones: prenatally and during puberty. The first, known as the organisational period, occurs before birth. During this time, sex hormones ‘organise’ or program the brain, setting it up to respond to hormones later in life. The second phase, known as the activational period, takes place during puberty, when the brain is ‘activated’ as the reproductive system switches on under the influence of these hormones.

The connection between the brain and gonads – called the hypothalamic-pituitary-gonadal (HPG) axis in males, and the hypothalamic-pituitary-ovarian (HPO) axis in females – is set up early in fetal life but becomes fully functional at puberty. In males, the axis operates continuously to produce sperm and keep them ready to mate. In females, the axis works in cycles, with ovulation typically occurring about once a month.

What’s the role of oestrogen in brain development?

You might be wondering, if testosterone ‘masculinises’ the body and brain of an unborn baby boy, does oestrogen from fetal ovaries play a role in ‘feminising’ the unborn baby girl’s brain?

Believe it or not, oestrogen plays little to no role at all!

Female brains do not require sex hormones to become ‘feminised’. Like the rest of the fetus, they are ‘destined’ to become female unless testosterone intervenes.

Oestrogen’s role in the developing female brain is thus a by-product of its absence, rather than presence. In fact, the embryonic female brain is shielded from the influence of maternal oestrogens (made by their mother and the placenta) by a molecule called alpha-fetoprotein made in the female fetal liver, which binds to any rogue oestrogen in the bloodstream and prevents it crossing into the fetal brain.29

Curiously, it’s oestrogen that is partly involved in organising the architecture of the male brain. Testosterone passes easily into the embryonic male brain where it latches on to androgen receptors, but it’s also converted to oestradiol (the main form of oestrogen) by an enzyme called aromatase. It’s oestradiol that’s responsible for ‘masculinising’ the male brain in utero, controlling the number of newborn neurons and how they connect or form synapses with each other.19

Taking it one step further, McCarthy’s research has found that exposing newborn female rats to oestradiol masculinises their brains, so much so that in adulthood, they exhibit male-like reproductive behaviours and mount other rats.

Mother Nature is selfish. And she also has a sense of humour.

Which part of the brain does what?

If you’ve ever attended a neurosurgery (or watched one on YouTube), you might have noticed that living human brains are neither pink nor blue. They’re a pulsating purplish grey. The wrinkly outermost layer of cortex, the grey matter, gets its name from its appearance, and it contains cell bodies of neurons, their branching extensions called dendrites and other cell types called glia. Running about a centimetre below the surface are white matter tracts – bundles of axons coated in whitish myelin that connect different regions of grey matter.

Traditionally, the brain is divided into two hemispheres (left and right), with four lobes per hemisphere: frontal, temporal, parietal and occipital. Each lobe has a few main jobs: occipital lobes process vision; temporal lobes process sound, speech and memory; parietal lobes integrate sensory input and movement; and frontal lobes, which are larger and more evolved by far in humans than any other creature, are involved in higher cognitive functions, such as planning, decision-making, problem-solving, abstract reasoning, processing social information and controlling voluntary movements.

But how do neuroscientists know which part of the brain does what? The opening line of neurologist Oliver Sacks’s masterpiece, The Man Who Mistook His Wife for a Hat, gives us a clue: ‘Neurology’s favourite word is deficit.’ In his book, Sacks told ‘inconceivably strange’ tales, each one a case study of patients managing neurological disorders and deficits. Deficits in function caused by a stroke, or a brain tumour, gave neurologists their first insight into what was called ‘localisation of function’.30 As Sacks wrote, the scientific study of the relationship between the brain and mind began in 1861 when French neurologist Paul Broca found speech problems always followed damage to a particular portion of the left temporal lobe.

This opened the way to mapping the human brain, ascribing specific roles – linguistic, intellectual, emotional, visual and so on – to different regions of the brain. During my PhD, I spent hundreds of hours placing tungsten micro-electrodes exactly four millimetres deep into the precise location in an occipital cortex where I knew with certainty that I could record inputs from the left or right eye. Similarly, neurosurgeons use stimulating electrodes to carefully map the brain before they pick up their scalpel, thus avoiding damaging critical regions.

Functional MRI (fMRI) and other modern brain-imaging technologies continue to provide insights into brain activity and structure. While it’s clear brain regions have specialised functions (like vision or hearing), cognitive processes like memory, social cognition or language emerge from the complex interactions of multiple brain areas working together. Rather than asking ‘where’ a function lives in the brain, neuroscientists now find it more insightful to ask ‘how’ functions arise from the dynamic and interconnected neural networks.

A particular job or trait is never ‘hardwired’ into a specific cortical location for life. Instead, brains are what is known as plastic, meaning they’re malleable and change their structure and function in response to experiences. During my tungsten micro-electrode recording sessions, I was able to manipulate an individual neuron’s preference for the left or right eye depending on whether one or the other eye was blindfolded. Other researchers have shown visual neurons can even learn to respond to sound if neural inputs from the ear are encouraged to reroute. This capacity for plasticity underlies your ability to learn and remember, and to recover from brain injuries such as a stroke.

Zoom in a little further and you’ll see the brain’s regional specificity is supported by diversity. Even the simplest of neural structures is made up of a huge assortment of cell types. For example, in the retina of the eye there are dozens of classes of neuron, and in the spinal cord more than one hundred different types of specialised neurons connect to muscles. Diversity comes about in the early embryo by way of chemical gradients and signalling molecules. Head-to-tail or left–right body patterns, for example, are determined by how near or far a cell is from a source of a chemical that influences which genes switch on or off, thereby determining what type of cell develops.

The diversity and the precise connections formed by many billions of neurons during in utero development underlie the wondrous capacity of your brain and mind. A brain that allows you to love, feel, move through the world, create artworks, send satellites into space and even, when damaged as Sacks’s patient’s brain was, ‘reach out his hand, take hold of his wife’s head, try to lift it off and put it on’, mistaking her for his hat.

ABOUT THE AUTHOR

Dr Sarah McKay is a Kiwi-born, Australian-based neuroscientist and science communicator who specialises in translating brain research into practical strategies to improve health, wellbeing, and performance.

After completing an MSc and DPhil in neuroscience at the University of Oxford, Sarah moved to Australia to undertake postdoctoral research on spinal cord injury. She then hung up her lab coat to focus on science communication and education, founding a company, Think Brain, dedicated to applied neuroscience and brain health.

Sarah has presented on ABC Catalyst, exploring brain health, biohacking, and longevity, and delivered a TEDx talk on the surprising neuroscience of afternoon naps.

Her work regularly features across print, radio, podcasts and television. S

She is the author of three books on brain health. The Women’s Brain Book: The Neuroscience of Health, Hormones, and Happiness was first published in 2018, with a fully updated second edition scheduled for release in July 2025. Baby Brain (2023) explores how pregnancy and motherhood shape the brain. Her latest book, Brain Health For Dummies, was released in early 2025.

Sarah lives on Sydney’s Northern Beaches with her Irish husband, two teenage sons, and a springer spaniel. They spend as much time as possible in or on the ocean — swimming, sailing, and surfing.

Visit Dr Sarah McKay’s website