EN / DA
Body and mind

Researchers find link between male sex hormones and ovarian disease

Polycystic ovary syndrome is the most common disorder among women of reproductive age and often leads to problems in becoming pregnant. Now scientists have found a link between polycystic ovary syndrome, elevated levels of male sex hormones, obesity and effects on the fetus.

Polycystic ovary syndrome (PCOS) is the most common disorder among women of childbearing age and often leads to difficulty in getting pregnant. Between 10% and 15% of all women, and up to 25% of obese women, have PCOS.

Now a new study shows that PCOS not only affects women but can also affect their unborn children.

“The high levels of male sex hormones and obesity in PCOS can affect how the placenta functions among pregnant women and thus also the fetus. Our study is the first to examine how PCOS affects all the proteins in both the placenta and in the fetal liver,” explains the researcher behind the study, Elisabet Stener-Victorin, Professor, Karolinska Institutet, Stockholm, Sweden.

Elisabet Stener-Victorin recently published the results in the International Journal of Obesity.

Examined changes in all proteins in the uterus and the fetus

The symptoms of PCOS include high levels of male sex hormones, which can lead to unwanted hair growth and acne. Women with PCOS also often have difficulty in getting pregnant because their menstrual cycles are irregular. In addition, obesity is very common among women with PCOS, and they have a greater risk of developing depression and anxiety.

In this new study, Elisabet Stener-Victorin investigated using mice how the mother’s obesity and elevated levels of male sex hormones affect the function of all proteins in both the placenta and in the fetal liver.

Protein function in the liver and placenta shows how the fetus is developing and under what conditions.

To examine this, the researchers first fattened up the mice, got them pregnant and then gave them high levels of male sex hormones in the last stage of pregnancy. Just before the mice gave birth, the researchers examined the activity of all proteins in the placenta and in the fetal liver.

The researchers found just under 5000 proteins in the placenta, of which 404 were phosphorylated, meaning they are active. In the fetal liver, the researchers found 5400 proteins, of which 474 were phosphorylated.

“We can compare our main finding, which has not previously been found, with the protein activity in mice that have not been exposed to either male sex hormones or fattening diets,” says Elisabet Stener-Victorin.

Changing how proteins are expressed

The researchers further examined the protein activity and how this differed between mothers with PCOS and other mothers. One finding was that ATP-citrate synthase proteins were downregulated in the placenta and that catechol-O-methyltransferase (COMT) proteins were expressed differently than normal.

The fetal liver had elevated levels of phosphorylated COMT if the mothers had been obese.

The researchers previously showed among mice that the offspring of mothers with PCOS have a greater risk of developing anxiety symptoms, and the changes in the activity of COMT may contribute to explaining this.

“We previously showed that the offspring of PCOS mice have an increased risk of developing anxiety, and here we showed changes in the mechanism regulating COMT in both the placenta and in the liver. Changes in the environment in which the offspring develop may explain why anxiety develops,” says Elisabet Stener-Victorin.

Children of normal-weight women with PCOS remain at higher risk

Although the study involved mice, Elisabet Stener-Victorin says that the knowledge can be used to obtain more insight into how PCOS affects people.

In the long term, the goal is to counteract PCOS in women to avoid the fetus being put at greater risks of also developing PCOS and becoming obese and of developing depression and anxiety.

“Obesity makes everything worse, so losing weight is still important for women who want to become pregnant. However, our experiment shows that male sex hormones are the dominant factor, so this is where we need to intervene for women with PCOS. This can be done using drugs or by lifestyle changes,” says Elisabet Stener-Victorin.

Another aspect of this story is that elevated levels of male sex hormones seem to be most strongly associated with problems in getting pregnant. This means that women with normal weight who have PCOS should also talk to their doctor if they want to become pregnant.

“Just a slight weight loss or exercise can probably reduce circulating male sex hormones among women with PCOS, thus reducing the risk of problems in getting pregnant and the risk of affecting the unborn child,” concludes Elisabet Stener-Victorin.

Mice exposed to maternal androgen excess and diet-induced obesity have altered phosphorylation of catechol-O-methyltransferase in the placenta and fetal liver” has been published in the International Journal of Obesity. In 2016, the Novo Nordisk Foundation awarded a grant to Elisabet Stener-Victorin for the project Maternal Androgen and Obesity: Effects on Placenta and Fetus Function, on Offspring Behavior and Metabolism and on Gut Microbiome Function.

Elisabet Stener-Victorin
Professor
Elisabet Stener-Victorin established her research group Reproductive Endocrinology and Metabolism at the Department of Physiology and Pharmacology in January 2015. She was previously with the Department of Physiology at University of Gothenburg where she held a VR granted Junior Research position, and since 2009 a Senior Research position. Her group’s research activities aim to yield new key information on the pathophysiology of polycystic ovary syndrome (PCOS), the most common female endocrine and metabolic disorder. Its etiology is not well understood, but genetic, epigenetic, and environmental factors have been implicated in its development. They also investigate the effect and mechanisms of acupuncture and/or exercise on reproductive function, hyperandrogenemia and insulin resistance as well as on key molecular pathways and epigenetic modifications in adipose and skeletal muscle tissues.