A hormone called GDF15 is the primary driver of morning sickness. Produced by the fetal part of the placenta, GDF15 floods the mother’s bloodstream during early pregnancy and acts directly on the brain to trigger nausea and vomiting. While doctors long suspected that hCG (the “pregnancy hormone”) was responsible, a landmark 2023 study published in Nature pinpointed GDF15 as the real culprit and explained why some women suffer far more than others.
How GDF15 Triggers Nausea
GDF15, short for Growth Differentiation Factor 15, is a hormone your body produces in small amounts even when you’re not pregnant. Once pregnancy begins, the placenta starts manufacturing it in much larger quantities. This surge of GDF15 travels through the bloodstream and binds to a highly specific receptor in the brain, activating the sensation of nausea and the urge to vomit.
The severity of morning sickness depends on two factors working together: how much GDF15 the placenta produces, and how sensitive the mother’s brain is to it. That sensitivity is shaped by how much GDF15 she was exposed to before pregnancy. Women who naturally have low levels of GDF15 in their blood before conceiving tend to be more sensitive to the sudden spike, and they experience worse symptoms. It’s essentially a tolerance issue. The brain hasn’t adapted to this particular signal, so when levels jump, the reaction is intense.
Researchers demonstrated this in mice. Animals exposed to a sudden, high dose of GDF15 lost their appetite and showed signs of nausea. But mice that were pre-treated with a long-acting form of the hormone beforehand didn’t react the same way when hit with a high dose. Their systems had adjusted.
Why Some Women Get It Worse
Genetics play a significant role in determining where you fall on the morning sickness spectrum. Some women carry a genetic variant that keeps their baseline GDF15 levels low outside of pregnancy. That variant is strongly associated with hyperemesis gravidarum, the severe form of pregnancy sickness that can lead to hospitalization, dehydration, and significant weight loss.
The genetics are surprisingly nuanced. If a mother carries the GDF15-lowering mutation, her pre-pregnancy levels are low, making her more sensitive to the rise during pregnancy. But if the fetus inherits that same mutation, the placenta actually produces less GDF15 during pregnancy, which can reduce symptoms. So the same gene variant can either worsen or lessen sickness depending on whether the mother or the baby carries it.
One of the most compelling pieces of evidence comes from women with beta thalassemia, an inherited blood disorder that causes naturally very high levels of GDF15 throughout life. These women experience little or no nausea during pregnancy. Their brains are already desensitized to the hormone long before conception, so the placental surge barely registers.
Other factors also influence how much GDF15 the placenta produces. Pregnancies with multiples tend to produce more. The sex of the fetus can play a role as well.
The Role of hCG, Estrogen, and Progesterone
For decades, hCG was the leading suspect behind morning sickness. It made intuitive sense: hCG rises rapidly in the first trimester and peaks around week 10, which roughly lines up with the worst period of nausea for most women. And studies have found that hCG levels tend to be higher in women with more severe nausea compared to women who feel fine.
HCG likely does contribute, but not in the way scientists originally thought. The hormone is structurally similar enough to thyroid-stimulating hormone (TSH) that at high levels, it can nudge the thyroid into producing extra thyroid hormones. This mild, temporary hyperthyroid state may amplify nausea in some women, particularly those with very high hCG levels early in pregnancy. The body doesn’t intend for this to happen; it’s essentially a side effect of hCG’s chemical resemblance to TSH.
Estrogen and progesterone also play supporting roles. Both hormones relax smooth muscle throughout the digestive tract, slowing the movement of food through the stomach and intestines. Estrogen in particular delays gastric emptying and reduces the contractions that normally push food along. Progesterone loosens the valve between the stomach and esophagus. The combined effect is a sluggish digestive system that can make nausea feel worse, even if these hormones aren’t directly triggering the nausea signal in the brain the way GDF15 does. This is the same mechanism behind the bloating and queasiness some women notice in the second half of their menstrual cycle, when estrogen and progesterone are at their highest.
Why “Morning” Sickness Is a Misleading Name
The hormonal picture explains why pregnancy nausea isn’t limited to mornings. GDF15 circulates constantly. Estrogen and progesterone slow digestion around the clock. While many women notice symptoms are worst after waking (possibly because blood sugar is low and the stomach is empty), nausea can strike at any time of day and, for some women, barely lets up at all. The name persists more out of tradition than accuracy.
Symptoms typically begin around week 6 of pregnancy, when placental GDF15 production ramps up, and peak between weeks 8 and 12. Most women see significant improvement by weeks 14 to 16, though a smaller percentage deal with nausea well into the second trimester or even throughout pregnancy.
What This Means for Prevention and Treatment
The discovery that GDF15 sensitivity is the core problem has opened up new thinking about treatment. The most promising concept is desensitization: gradually raising a woman’s GDF15 levels before pregnancy so that the placental surge doesn’t hit an unprepared brain. Researchers are exploring whether metformin, a widely used diabetes medication already known to raise GDF15 levels, could serve this purpose if taken before conception. Clinical testing of this prevention strategy is in early stages.
Another avenue targets the GDF15 receptor in the brain directly. Because GDF15 binds to a single, very specific receptor called GFRAL, blocking that receptor could in theory shut down the nausea signal without affecting other systems. The specificity of this receptor makes researchers more confident that an effective targeted therapy is possible.
For now, understanding the hormonal mechanism can at least explain something that often feels random and frustrating. The severity of your morning sickness isn’t about what you ate, how well you’re managing stress, or whether you’re “doing pregnancy wrong.” It’s driven by a mismatch between your baseline hormone exposure and the flood your placenta produces, shaped largely by genetics you had no control over.