How PCOS Affects Future Generation of Men

According to a study published in Cell Reports Medicine, sons of women with polycystic ovarian syndrome (PCOS) are three times as likely to develop obesity. The findings, according to the Karolinska Institutet researchers, reveal a hitherto unknown danger of passing PCOS-related health problems down through generations via the male side of the family.
PCOS is caused by the ovaries releasing an abnormally high level of the sex hormone testosterone. The disorder affects approximately 15% of women of reproductive age globally and might make it difficult to become pregnant. Furthermore, the disorder is linked to a number of health issues, including diabetes, obesity, and mental illness. Daughters of PCOS moms are five times more likely to develop the illness.

Although it is unclear how boys of PCOS mothers are affected, evidence indicates that they are more prone to develop weight and hormone issues. In the newly published study, the researchers examined both registry data and animal models to assess whether and how PCOS-like features are handed on from moms to their sons. The registry study includes nearly 460,000 sons born in Sweden between July 2006 and December 2015.

Approximately 9,000 of these were sons of PCOS mothers. The youngsters that were obese were subsequently identified by the researchers.

“We discovered that sons of women with PCOS have a threefold risk of obesity and of having high levels of ‘bad’ cholesterol, which increases the risk of developing insulin resistance and type 2 diabetes later in life,” says Elisabet Stener-Victorin, professor at the Department of Physiology and Pharmacology, Karolinska Institutet who led the study.

These findings were confirmed in a mouse study in which researchers examined male offspring of female mice fed either a standard diet or a diet high in fat and sugar before and during pregnancy, and were exposed to high levels of the male sex hormone dihydrotestosterone during pregnancy to mimic the pregnancy of normal weight individuals and obese women with PCOS. The male mice were then fed a regular diet until they reached adulthood, at which point their fat distribution and metabolism were studied.

“We could see that these male mice had more fat tissue, larger fat cells, and a disordered basal metabolism, despite eating a healthy diet,” says Elisabet Stener-Victorin.

To test the offspring’s reproductive function and if physiological features may be passed down from generation to generation, first-generation male mice were mated with healthy female mice that had not been subjected to male sex hormones or a high-fat, high-sugar diet.

The entire procedure was repeated in the second generation to reach the third generation, which was the first to be unaffected by the maternal ailment.

“Through these experiments, we can show that obesity and high levels of male hormones in the woman during pregnancy can cause long-term health problems in the male offspring. Their fat tissue function, metabolism, and reproductive function deteriorate, which in turn affects future generations,” says Qiaolin Deng, associate professor at the same department and one of the researchers behind the study.

“These findings are important because they highlight the risk of passing health problems down through the male side of a family, highlight the risk of passing this kind of health problem, and they may help us in the future to find ways to identify, treat and prevent reproductive and metabolic diseases at an early stage,” says Elisabet Stener-Victorin.

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