GDF15 Hormone Sensitivity Sparks Hope for Managing Pregnancy Sickness

December 18, 2023

Mohd Aasim

Pregnancy sickness, or hyperemesis gravidarum, is a common condition affecting seven out of ten women during pregnancy. Until recently, the reasons behind this phenomenon remained largely unknown. However, groundbreaking research led by a team has shed light on a potential contributor to the risk of pregnancy sickness: sensitivity to a hormone called GDF15, abundantly produced during pregnancy.

Even in milder cases, pregnancy sickness can significantly impact the quality of life for pregnant women. Severe forms, affecting 1% to 3% of women, lead to extreme nausea and vomiting, causing weight loss and dehydration. This condition ranks as the most common reason for hospital admissions in the first three months of pregnancy, with implications for both maternal and fetal health.

Research has linked pregnancy sickness to adverse pregnancy outcomes, and its effects can persist beyond childbirth, causing psychological distress and impacting future conception decisions. The lack of detailed understanding surrounding its causes hinders treatment development and contributes to the stigma associated with this condition.

GDF15, a hormone known to suppress food intake in mice, emerged as a potential culprit. This hormone, abundantly present in human placenta and at high concentrations in the blood of pregnant women, has been under investigation as an obesity therapy. While early trials confirmed its appetite-suppressing effects in humans, it also induced nausea and vomiting, making it a plausible candidate for pregnancy sickness.

The research team utilized various methods to explore how GDF15 contributes to the risk of pregnancy sickness. Blood samples from pregnant women experiencing sickness and those without were analyzed, revealing higher GDF15 levels in the former group. However, substantial overlap in GDF15 levels suggested additional factors influencing the risk of sickness.

Examining natural DNA variations in future mothers, the researchers identified changes near GDF15 as significant determinants of pregnancy sickness risk. A rare genetic mutation affecting GDF15 protein makeup was associated with a higher risk of sickness. Lab studies revealed that this mutated GDF15 molecule became trapped inside cells, hindering the transport of “normal” GDF15. Healthy individuals with this mutation exhibited lower GDF15 levels in their blood.

Further investigations uncovered that common DNA changes near GDF15, prevalent in 15% to 30% of people, lowered hormone levels, increasing the risk of pregnancy sickness. Interestingly, women with thalassaemia, a blood disorder associated with high GDF15 levels, reported less nausea and vomiting during pregnancy.

The paradoxical finding that higher pre-pregnancy levels of GDF15 reduce the risk of pregnancy sickness may be explained by a hormone sensitivity phenomenon resembling memory. Mice with consistently elevated GDF15 levels showed reduced responsiveness to acute surges in GDF15.

These findings suggest potential treatment approaches: desensitizing women to GDF15 by increasing its levels before pregnancy or blocking its action during pregnancy. However, the challenge lies in developing safe and acceptable strategies for women at risk of this debilitating condition.

In conclusion, the research provides crucial insights into the role of GDF15 in pregnancy sickness and offers a roadmap for potential treatments. By unraveling the complexities of hormone sensitivity, the medical community can work towards addressing this condition, improving the lives of pregnant women and reducing the associated stigma.

Journal Reference