By Dr. Vinu Jyothi, MD, MPH and Dr. Senthil Samy, PhD
PCOS is a common condition that affects approximately 20% of women of childbearing age worldwide and is a condition that can make it difficult to get pregnant. PCOS is caused by the ovaries producing too much of the sex hormone testosterone—hyperandrogenism. 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, the long-term effect of PCOS on offspring, especially male offspring is poorly understood and has received little attention.
A latest study discovered that sons of women with polycystic ovary syndrome (PCOS) are three times more likely to develop obesity as their peers. The study is published in the Journal Cell Reports Medicine by researchers from Sweden’s Karolinska Institutet. Using clinical registry data and mouse model, and the results of a prior case control study, these researchers determined if and how PCOS-like traits are passed from mothers to their sons and then confirmed their findings experimentally.
This study findings highlight a previously unknown risk of passing PCOS-related health problems across generations through the male side of a family. “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 lead investigator Elisabet Stener-Victorin, PhD, professor at the department of physiology and pharmacology, Karolinska Institutet.
“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 Qiaolin Deng, PhD, associate professor at the department of physiology and pharmacology, Karolinska Institutet.
The study also characterized how metabolic and hormonal features of sons could be impacted. “Although a distinct phenotype of male offspring related to PCOS has not yet been defined, sons born to mothers with PCOS display increased body mass index (BMI), insulin resistance, and prepubertal signs of reproductive dysfunction, with increased anti-müllerian (AMH) hormone levels, indicating increased Sertoli cell number,” the investigators described. They also found changes in the expression of small noncoding RNAs in the sperm of male offspring (mouse model), down three generations.
Together with the team’s recent findings that daughters of women with PCOS are five times more likely to be diagnosed with PCOS, and also that prenatal androgen-exposed first-generation male offspring develop an aberrant reproductive and metabolic phenotype, the overall results, they suggested, “strengthen the hypothesis that the PCOS may be implicated beyond generation, predisposing not only daughters but also their sons.”
Altogether, this research study has detailed long-term adverse effects of obesity and prenatal androgen excess during pregnancy leading to transmission of metabolic and reproductive alterations across generations via the male germline.
While such research updates indicate matter of concern but they also pave the way for developing novel strategies to deal with PCOS at an early level. “These findings are important because they highlight the risk of passing health problems down through the male offspring, and they may help us in the future to find ways to identify, treat, and prevent reproductive and metabolic diseases at an early stage,” Stener-Victorin stated.
These results significantly increase our understanding of the long-term health of kids whose moms have PCOS. Prior to conception, primary care physicians and obstetricians should think about diagnosing women with PCOS and providing early therapies like weight management and methods to assist prevent issues like diabetes, heart disease, and blood vessel illnesses. To reduce morbidity, family practitioners and pediatricians should think about keeping a closer eye on kids after birth. Increased parental understanding may contribute to better child outcomes.
While this evidence suggests that the daughters of women with PCOS are more likely to be diagnosed with PCOS when they reach adulthood (proven only among the native Swedish population) than if they were born to mothers without PCOS, it remains unclear whether this relationship is common worldwide or the relationship may not be as severe as we observe in this study. Besides, although such reports could be alarming but beneficial in terms of taking this as a model to develop early diagnostic biomarkers so as to deal with PCOS at early stage prospectively. It is certainly possible that further research will pave the way for potential therapeutic strategies to manage PCOS efficiently or cure in the future.
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