How B cells and androgens contribute to the development of PCOS

In a recent study published in e-lifeinvestigators are using a mouse model to assess the role of B-cell frequency in the pathogenesis of polycystic ovary syndrome (PCOS).

Contrary to previous hypotheses, our findings indicate that B cells are not the primary mediators of PCOS pathogenesis. Instead, these cells amplify the phenotypic expression of symptoms. The current study also reveals the role of androgen receptors in changes in B-cell counts in patients with PCOS.

study: Role of B cells in immune cell activation in polycystic ovary syndrome. Image credit: mi_viri / Shutterstock.com

What is PCOS?

PCOS is a hormonal disease characterized by a massive increase in androgen production by the ovaries. The term “PCOS” is derived from the numerous cysts, which are fluid-filled sacs that develop on the surface of the ovary.

PCOS is the most common hormonal disorder worldwide, affecting 5-18% of women of reproductive age. Symptoms of PCOS include rapid weight gain, irregular menstruation, and excessive hair growth. Acne. Importantly, PCOS is the most common cause of female infertility.

The underlying cause of PCOS remains unknown. However, researchers believe that interactions between genetic and environmental factors contribute to disease development. Previous studies have hypothesized that B cells play a central role in her PCOS, but the mechanism of this association remains unclear.

Studies on μ heavy chain knockout mice (MuMt)^–;B^null) are mice genetically unable to produce mature B cells, and it has been suggested that B cells amplify the metabolic effects of disease, particularly diabetes and insulin resistance. Because type 2 diabetes (T2D) and hyperthyroidism are both autoimmune diseases and are strongly correlated with PCOS, scientists have attempted to investigate the autoimmune triggers of PCOS, with continued success. not.

research result

In the present study, investigators assess B-cell frequencies, hyperandrogenemia, and previously hypothesized factors associated with cystogenesis and inflammation. autoantibodies.

The researchers began by characterizing the B-cell lineage using 15 PCOS-positive and 22 PCOS-negative women as test and control groups, respectively. The study group met all three Rotterdam criteria, including polycystic ovarian morphology, amenorrhea, and hirsutism, in addition to significantly higher levels of androstenedione and testosterone.

Although naive B-cell levels were identical between both groups, mature B cells from PCOS women lacked CD27 and immunoglobulin D (IgD) cell surface marker (CD27) expression.^– IgD^–). Serum antibody analysis similarly revealed that the PCOS group had higher free androgen index and testosterone, as well as upregulated circulating IgM. These results were significant even after adjusting for body mass index (BMI).

Interestingly, there was no difference in circulating IgG, but women with PCOS had lower IgA titers. “

Human IgG antibodies were transferred from 4 PCOS and control females into wild-type mice to determine whether POCS has autoimmune relevance. No differences were observed in the ovulatory cycle of these mice. However, patients receiving PCOS-positive IgG gained weight three weeks after treatment.

To assess the role of androgens in B-cell composition and frequency, we used a dihydrotestosterone (DHT)-induced PCOS mouse model. The three study groups included mice that received DHT subcutaneously, controls, and mice that received both DHT and an androgen receptor (AR) suppressor.

After 4 weeks of treatment, DHT-only mice gained weight and experienced estrous cycle disruptions, which were not reported in the other two groups. B-cell composition and frequency were significantly altered in the DHT-treated group compared to the other groups. These mice also exhibited severely affected ovarian tissue and PCOS-like symptoms.

The researchers then transplanted B cells from PCOS-like mice into B-cell-deficient mice. Here, the test group did not exhibit PCOS-like symptoms.

To definitively determine whether lack of B cells could confer immunity to PCOS development, the researchers subcutaneously administered DHT to knockout mice lacking B cells. These mice developed PCOS-like symptoms at 4 weeks after treatment.

Conclusion

Women with hyperandrogenism experience alterations in B-cell morphology and frequency, as well as upregulation of circulating IgM in blood and tissues. This indicates a role for androgens in the development of PCOS. However, it does not ignore the influence of B cell or IgM mechanisms.

When DHT is administered to mice, it produces PCOS-like symptoms in metabolic, immune, and reproductive tissues. These include changes in B cells that are identical to PCOS, reflecting the role of androgens in causing the B cell changes observed in PCOS.

Introduction of PCOS-like B cells into B cell-deficient mice does not induce PCOS symptoms. Thus, although B cells may amplify the effects of pre-existing her PCOS, they cannot cause disease.

In contrast, the development of PCOS is observed when androgens alone are introduced into B-cell-deficient mice. This observation indicates that androgens are the causative factor for her PCOS and that the absence of B cells does not presume immunity from her PCOS.

Taken together, the findings elucidate the underlying mechanisms and causative agents of PCOS. Hyperandrogenism, caused by genetic and environmental interactions, independently causes PCOS-like symptoms such as B-cell alterations, menstrual disturbances, and significant weight gain.

Compared to previous hypotheses, we found that B cells are not capable of causing PCOS, but are involved in the proliferation of this condition. Her B cells of a PCOS-positive woman show profound alterations in cell surface markers, which may be used as early indicators of this disease.

Most importantly, we showed that B cells are not central mediators of systemic inflammation or impaired glucose metabolism in PCOS, and the lack of these lymphocytes induces a PCOS-like phenotype after DHT exposure. because it cannot prevent “