How Pregnancy and Motherhood Reshape the Human Brain

Few transformations in the human body are as intense as pregnancy. To sustain the developing fetus, a woman’s body starts accumulating fluid, her heart pumps blood faster, and her lung capacity diminishes as the fetus grows and occupies more space inside the mother’s womb. The growing placenta also pumps unfamiliar hormones into the soon-to-be mom’s body, which is simultaneously flooded with familiar hormones, including estrogen and progesterone that surge to levels tens or hundreds of times higher than those seen in non-pregnant women.

While scientists have characterized many of these physiological adaptations, for years, they overlooked how pregnancy, as well as motherhood, could reshape a key organ of the human body: the brain.

Over the last two decades, though, scientists have started to examine the maternal brain more closely. They have explored the cellular changes induced by pregnancy and motherhood in animal models, how these events transform the human brain, and the implications these changes might have on women’s health.

Remodeling the Brain for Parenthood

For many first-time moms, parenting feels like a continuous learning experience. At the same time, some aspects of parental care seem to come naturally, as if they were hardwired in the brain.

The instinctive nature of parental behavior is not exclusive to humans. Caring for offspring is an adaptation essential for the survival of many animal species and therefore relies on conserved brain circuits that have been shaped by evolution over generations.

In the 1960s and 1970s, scientists started to explore parental behavior in animal models and showed that virgin female rodents, which typically avoid unfamiliar pups, could either exhibit maternal care spontaneously or after receiving estrogen, progesterone, and prolactin hormones, which surge in females about to give birth.^1,2 Evidence from animal studies also suggested that the hypothalamus—one of the oldest and tiniest regions of the brain—played a role in maternal behavior.³ Yet, it took researchers another 40 years and many methodological advances to dissect the components of the neural circuitry that control parental behavior in detail.

In the mid-2010s, work by biologist Catherine Dulac’s team at Harvard University revealed that a subset of galanin-expressing neurons found in the medial preoptic area (MPOA) of the hypothalamus are critical for parenting in both male and female rodents.⁴ These findings intrigued neuroscientist Johannes Kohl, who joined Dulac’s lab in 2014 as a postdoctoral researcher. “I found [these results] absolutely fascinating,” Kohl said. “You have a very small population of neurons, we're talking about 8,000 to 10,000 neurons out of a total of 100 million in the mouse brain, that is somehow linked to the control of a very complex social behavior.”

In Dulac’s lab, Kohl mapped how these MPOA galanin-expressing neurons communicated with the other brain regions to control different aspects of parenting. This anatomical work revealed a “shockingly complex picture,” he said, showing that these neurons received inputs from and projected to more than 20 brain regions. The researchers also found that discrete pools of the galanin-expressing neurons controlled specific aspects of parental behavior, such as the motivation to interact and groom pups, painting a more detailed picture of how these neurons orchestrate this complex behavior.⁵

Now in his own lab at the Francis Crick Institute, Kohl probes how malleable the circuits mediating instinctive behaviors are. When it comes to parenting, he explained that while virgin female mice can exhibit spontaneous parental behavior, they are not very good at it, oftentimes ignoring the pups. “But mothers are 100 percent parental,” he added. “[So] how does the same animal go from this low parental state to this extremely high parental state over the course of three weeks?”

Scientists had proposed that hormonal changes around the time of giving birth triggered the transition to motherhood. Many researchers thought these hormonal changes primed the female brain and “awakened” a maternal state.⁶ “That makes sense, but it seems like a very weird way of designing a system,” Kohl explained. “During pregnancy, you have three weeks of time to prepare for what is the most dramatic change in a female's life. Wouldn't it make sense if the system somehow prepared for that?”

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By focusing on how female mice interacted with pups, Kohl’s team showed that females became highly parental already in late pregnancy, that is, a few days before pups were to be born. The researchers also found that estradiol and progesterone, two hormones that surge during pregnancy, acted on the MPOA galanin-expressing neurons to remodel the circuit and prepare the female brain to execute infant-directed behaviors.⁷

While animal studies by Kohl and others have uncovered the circuit and cellular changes associated with maternal behavior, Emily Jacobs, a neuroscientist at the University of California, Santa Barbara, is looking macroscopically at the brains of soon-to-be human moms to understand how pregnancy shapes the anatomy and function of their brains.

For years Jacobs has been interested in understanding how the endocrine system influences the nervous system—a field that, according to her, has been well-documented in animal studies but overlooked in human neuroimaging. “My life's work has just been sort of translating [the work happening in models] to understand the power of hormones in the human brain,” she said.

Around 10 years ago, Jacobs’ team devised a precision neuroimaging approach that captured brain changes not as snapshots of specific timepoints but as continuous movies by taking multiple functional magnetic resonance imaging (fMRI) scans over time. Using this method, the researchers performed daily fMRI scans on a non-pregnant woman, and the temporally rich data allowed the team to track changes in brain function and how they correlated with estrogen and progesterone fluctuations across the human menstrual cycle.⁸ After realizing that her team had devised a way to follow brain function dynamics over time, Jacobs was convinced that she could apply this same approach to study brain changes during pregnancy.

To map how the maternal brain adapts to pregnancy as it unfolds, Jacobs’ team followed a woman from preconception to up to two years postpartum. Pregnancy was associated with marked reductions in gray matter volume and cortical thickness, revealing extensive remodeling of the brain during pregnancy itself. This aligned with previous neuroimaging work showing gray matter volume reductions before and after pregnancy.⁹ “It was really neat to see the week-by-week change in gray matter volume,” Jacobs explained. “We really didn't have any idea about what the sort of temporal pace of that change would be. It was really neat to be able trace those trajectories and realize it's pretty linear.”

Jacob is now focusing on pregnancy’s molecular signatures, using high-throughput proteomics to assess thousands of blood proteins associated with different body systems and determine which ones track with the brain changes they previously described. Additionally, her team is launching a much broader maternal brain project that will include a more diverse sample of women to understand which pregnancy signatures may be universal or unique to each woman.

Leaving a Long-Lasting Mark

Understanding the brain remodeling that occurs during pregnancy and its effects on moms has also been a goal of Elseline Hoekzema and Susana Carmona, neuroscientists at the Amsterdam University Medical Center and Gregorio Marañón Health Research Institute, respectively. According to Jacobs, their neuroimaging study published in 2017 is a landmark for the human maternal brain field.¹⁰ “That really gave birth to this field of the maternal brain or the parental brain,” she emphasized.

Carmona explained that the story behind that study started around 10 years earlier, when she, Hoekzema, and Erika Barba-Müller, currently a psychologist and psychotherapist, were members of the laboratory of neuroscientist Oscar Vilarroya at the Autonomous University of Barcelona. Back then, the trio wondered how women’s brains would change during their transition to motherhood—a topic they found out had been scarcely researched in humans.

In the study, the researchers scanned the brains of first-time moms before and after pregnancy and found pronounced gray matter volume reductions that were associated with the moms’ attachment towards their own babies.¹⁰ “When the first and main paper finally came out in 2017, it felt a bit like the birth of a baby after an almost 10-year pregnancy!” Hoekzema wrote in an email.

The team also showed that these morphological changes lasted up to two years after childbirth—a finding Carmona and Hoekzema revisited and reported that could actually last for up to six years.¹¹ Carmona noted that while these changes do not persist in all women, for most they do. “We don't know if it's pregnancy or child-rearing, but changes seem to remain several years or decades postpartum, opening the door to the fact that they might be [for a] lifetime,” she added.

On the other side of the Atlantic Ocean, Liisa Galea, a neuroscientist at the Center for Addiction and Mental Health, also felt compelled to investigate the effects of pregnancy and motherhood on the brain after experiencing pregnancy firsthand. “It was such a profound experience. Afterwards, it’s not just about pregnancy; it’s a lifelong commitment that you have to the baby that you've produced,” she said.

Galea became interested in studying the long-lasting effects of these natural female events on the aging brain. Previous neuroimaging studies looking at thousands of middle-aged women’s brains revealed that mothers showed fewer signs of brain aging than women who did not have children.¹²

Galea’s team focused on the hippocampus, a brain region essential for learning and memory that the researchers had previously shown undergoes extensive remodeling during pregnancy and postpartum.^13,14 To investigate the mechanisms mediating pregnancy’s long-lasting effects in the brain, the researchers compared an array of cellular and molecular markers in rat moms right after they gave birth and in middle age with females that had never given birth. Rat moms exhibited higher levels of proteins involved in synaptic plasticity in their hippocampi, and this brain structure did not show the expected age-related reduction in neural stem cells, suggesting that pregnancy and postpartum are associated with long-lasting molecular changes in the female brain.¹⁵

As Galea investigated the effects of parity, that is, having given birth, on the aging brain, she was also intrigued by the relationship between pregnancy and the risk of Alzheimer’s disease (AD), which affects more women than men.¹⁶ Galea explained that, even though the literature presents contrasting findings, some studies suggest that parity is associated with an early onset of the disease and that having given birth five or more times increases women’s risk of AD.^17,18

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To study this relationship more closely, Galea and her team looked at the effects of parity on memory, neurogenesis, and neuroimmune markers in rats with or without copies of the apolipoprotein E (APOE) ɛ4 allele, a genotype associated with an increased risk of AD.¹⁶ They found that middle-aged rat moms that carried the APOE ɛ4 allele showed opposite effects of parity on the brain, including decreased neurogenesis and poorer performance on a memory task.¹⁹ “The students call it the parity paradox,” Galea explained. “Previous parity seems to have more beneficial effects in one genotype, but not in the other. In the other genotype [APOE ɛ4], it might actually push your risk a little bit further.”

From Brain Re-Sculpture to Women’s Health

While accumulating evidence from basic and human research has expanded what researchers know about the effects of pregnancy and motherhood on the brain, many questions remain to be answered.

In the field of human neuroimaging, researchers are beginning to explore how the constantly documented anatomical changes may reflect changes in brain function. Work by Hoekzema’s team, for instance, has shown that becoming a mom is linked to functional brain plasticity, particularly in the default mode network, a collection of interconnected brain areas that become less active when a person pays attention to external stimuli. ^20,21 This may provide mothers with adaptive advantages that are important for the mother-infant relationship.²⁰

Meanwhile, Carmona’s team recently showed that neuroanatomical changes in the brain’s amygdala were associated with increased perinatal depression symptoms, suggesting that some brain morphological changes might create windows of vulnerability to psychiatric conditions.²²

Both Carmona and Jacobs pointed out that women want to know what happens in their bodies during such a life-changing moment, adding that women are very motivated to participate in studies that will shed light on these changes.

“Women are tired of confronting a medical system that was never designed to serve them. They want basic answers about their bodies,” Jacobs explained. “Matrescence is such a beautiful time, and for scientists to be able to approach it with awe and curiosity is just such a special thing.”