Men born to obese women are more likely to be overweight at birth and develop metabolic complications later in life, including liver diseases and diabetes.
Image credit: University of South Australia
The way in which male sex hormones activate signaling pathways in the developing liver is responsible for this.
This is the result of a new study led by researchers at the University of South Australia (UniSA) focusing on the effects of maternal obesity on fetal liver androgen signaling.
Male fetuses of obese pregnant women have different signals activated by male sex hormones in the liver, encouraging them to prioritize growth at the expense of their health.
UniSA researcher Dr. Ashley Meakin says that androgens give males their masculine traits and are crucial for their development. However, excess androgens cause male fetuses to grow too large, leading to birth problems and impairing liver function in adulthood.
Female fetuses exposed to excessive testosterone due to maternal obesity are inclined to turn off the androgen pathway in the liver, limiting their growth and reducing the risk of metabolic disorders in adulthood.
„We know that there are gender-specific differences in metabolic disorders in later life in response to maternal obesity,“ says Dr. Ashley Meakin. „Men are more susceptible to non-alcoholic fatty liver disease and diabetes in adulthood if their mother is obese during pregnancy and their birth weight is over 4 kg (9 lb 15 oz). They are genetically predisposed to prioritize androgens, as this supports the development of masculine traits, including size, but too much androgen is bad.“
– Dr. Ashley Meakin, UniSA researcher
The lead author of the study, Professor Janna Morrison, head of the „Early Origins of Adult Health“ research group at UniSA, says that it is important for women to strike a balance and maintain proper nutrition during pregnancy to provide optimal conditions for their unborn child to thrive.
„There is also a risk of offspring being undernourished during pregnancy,“ she says. „If you are too small, too large, born too early, or male, you are more susceptible to negative consequences later in life. You need the Goldilocks pregnancy: you have to be the right size and born at the right time.“
Prof. Morrison says that reducing obesity and associated health problems from the womb to adulthood will be a tough battle if society does not change its approach to nutrition.
„As a society, we urgently need to address obesity. If children were educated early on the importance of healthy nutrition, it would have an impact into adulthood, including during pregnancy, where proper nutrition is so crucial.“
Dr. Meakin suggests that nutritional supplements correcting nutritional imbalances during pregnancy could offer the fetus the best chances of optimal development in the meantime.
The liver androgen signaling study, recently published in Life Sciences, is part of a series of studies by Prof. Morrison and colleagues examining the effects of maternal undernutrition and overnutrition on the placenta, heart, lungs, and liver.
Males born to obese women more likely to develop metabolic complications in later life
Video credit: University of South Australia
University of South Australia
Meakin, AS, et al. (2024). Maternal obesity impacts fetal liver androgen signaling in a gender-specific manner. Life Sciences. doi.org/10.1016/j.lfs.2023.122344.