Immune Dysfunction May Be a Novel Target for PCOS Therapy, Study Finds
The effects of hyperandrogenism on the immune system are largely unknown.
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A new study from the Karolinska Institute explores how polycystic ovary syndrome (PCOS) impacts the immune system, revealing that immune cell populations were affected across reproductive, metabolic and immunological tissues in different ways, potentially opening up new avenues for targeted treatments. The paper was published in Advanced Science.
PCOS and the immune system
PCOS is a reproductive disorder that affects 8–13% of women. Characterized by an excess of male sex hormones, called androgens, PCOS can cause irregular menstruation, issues with fertility, excess hair growth, acne and other metabolic concerns. Though several factors can contribute to the risk of developing the disease, the exact cause of PCOS is still unknown.
The condition has previously been associated with various metabolic conditions such as type 2 diabetes and obesity. Immune dysfunction has also been linked to various features of PCOS including reproductive complications and metabolic disease, but the effects of hyperandrogenism on the immune system are largely unknown.
Immune cell effects are site-specific
To understand the potential effects on the immune system, the researchers used flow cytometry to analyze immune cell populations in blood and secondary lymphoid organs from PCOS-like mice models exposed to dihydrotestosterone (DHT), representing hyperandrogenism.
Surprisingly, the team found the effects of hyperandrogenism on immune cells were site-specific; cell populations were affected across reproductive, metabolic and immunological tissues in different ways.
The DHT-exposed mice had an altered immune profile in the uterus. Eosinophil populations were dramatically reduced, despite them not expressing androgen receptors. Natural killer cells and related cytokine levels were also altered, showing higher numbers compared to controls.
“It is well known that immune cells play a crucial role in reproduction,” said Sara Torstensson, lead author of the study and PhD candidate at the Karolinska Institute, speaking to Technology Networks. “The dramatic changes in the immune profile in the uterus of our mice is therefore intriguing as this could be a contributing factor to the reduced fertility and pregnancy complications that are associated with PCOS.”
The frequency of macrophages decreased in the ovaries of DHT-exposed mice, though eosinophils and natural killer cell populations were unchanged.
Immune cells in adipose tissue were also impacted in the DHT-exposed mice. Eosinophil populations were decreased, while natural killer cell populations displayed a higher expression of the cytokine CD69. The DHT-exposed mice were also insulin-resistant, despite an unaltered fat mass.
“Hyperandrogenism, the key feature of PCOS, has a wide but differential effect on various immune populations. This clearly shows that the immune system is affected in PCOS and could be an important part of the pathology,” said Torstensson.
Working toward targeted treatments
Furthermore, the mice were co-treated with an androgen receptor antagonist, which prevented the various alterations seen in the DHT-exposed group.
“Since concurrent treatment with an androgen receptor antagonist prevented many changes in the mouse model we used in our study, combination therapies that include both anti-androgens and other drugs that target specific altered immune pathways could be explored. These findings also suggest that hormone therapy for PCOS needs to consider the broader effects on the immune system,” said Torstensson.
“As the study shows that hyperandrogenism affects different tissues in unique ways, any possible treatments would have to be carefully tailored to target specific tissue dysfunctions,” Torstensson added. “While neither this nor our previous study indicate that the immune system is causing PCOS, it is important to understand that hyperandrogenism is affecting the immune system and potentially also immune function.
Reference: Torstensson S, Ascani A, Risal S, et al. Androgens modulate the immune profile in a mouse model of polycystic ovary syndrome. Adv Sci. 2024:2401772. doi: 10.1002/advs.202401772
This article is a rework of a press release issued by Karolinska Institute. Material has been edited for length and content.
