Moms’ PCOS May Affect the Health of Future Male Generations

A new study highlights possible health risks related to polycystic ovary syndrome (PCOS) that can be passed down through the male side of families, revealing that sons of women with PCOS are three times more likely to develop obesity. The research is published in Cell Reports Medicine.

Family histories of PCOS

PCOS is a common condition that affects approximately 15% of women worldwide and negatively impacts ovary function. Along with difficulties conceiving, PCOS is associated with various health problems such as diabetes and obesity.

There are also familial links underlying PCOS – the risk of developing the condition is often increased for women who have close female relatives with PCOS. Strikingly, daughters of women with PCOS have a fivefold higher risk of developing the condition themselves, though there are currently no specific genes that have been linked to the condition.

However, some studies have suggested that the sons of women with PCOS may also be impacted by the condition. Previous research has suggested they may be at a higher risk for weight and hormonal problems, though this is not well understood.

In the current study, researchers combined information from data registries and experimental mouse models to investigate if and how mothers may pass health risks related to PCOS to their sons.

Threefold higher risk of obesity

To investigate the generational effects of PCOS, researchers gathered registry data from over 460,000 sons born in Sweden during the period 2006–2015 – almost 10,000 of whom were born to mothers with PCOS – and identified which of these children were obese.

“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,” said Prof. Elisabet Stener-Victorin, senior author of the study and a professor at the Karolinska Institute’s Department of Physiology and Pharmacology.

Next, the researchers turned to experimental mouse studies to confirm these findings. Female mice, both before and during pregnancy, were fed either a standard diet alone or a high-fat, high-sugar diet along with exposure to the male hormone dihydrotestosterone. These conditions were designed to mimic normal weight and obese women with PCOS, respectively, as hormone imbalances such as raised testosterone levels are a common feature of PCOS.

The male offspring of these mice were fed a standard diet until they reached adulthood, at which point the researchers assessed their fat distribution and metabolism. This revealed several abnormalities in the male offspring of the PCOS-like group. “We could see that these male mice had more fat tissue, larger fat cells and a disordered basal metabolism, despite eating a healthy diet,” said Stener-Victorin.

These first-generation mice were then mated with healthy female mice to understand if and how these characteristics may be passed on to second and even third generations of offspring, discovering that the third generation – in humans, this would be the original mothers’ great-grandchildren – was the first to be unaffected.

“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,” said Dr. Qiaolin Deng, study co-author and associate professor at the Karolinska Institute.

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

Reference: Risal S, Li C, Luo Q, et al. Transgenerational transmission of reproductive and metabolic dysfunction in the male progeny of polycystic ovary syndrome. Cell Reports Medicine. 2023. doi: 10.1016/j.xcrm.2023.101035

This article is a rework of a press release issued by the Karolinska Institute. Material has been edited for length and content.