The role of B cells in immune cell activation in polycystic ovary syndrome

Ascani, Angelo; Torstensson, Sara; Risal, Sanjiv; Lu, Haojiang; Eriksson, Gustaw; Li, Congru; Teshl, Sabrina; Menezes, Joana; Sándor, Katalin; Ohlsson, Claes; Svensson, Camilla I.; Karlsson, Mikael C. I.; Stradner, Martin; Obermayer–Pietsch, Barbara; Stener-Victorin, Elisabet

doi:10.1101/2023.01.26.525671

Cited by 3 publications

(7 citation statements)

References 54 publications

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“…4b). However, in line with previous findings 21 , DHT-exposed mice displayed an increased body weight compared to control (Supplementary Fig. 4a), which was due to higher lean mass in DHT-exposed mice (Supplementary Fig.…”

Section: Resultssupporting

confidence: 92%

Androgens modulate the immune profile in a mouse model of polycystic ovary syndrome

Torstensson,

Ascani,

Risal

et al. 2024

Preprint

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Polycystic ovary syndrome (PCOS) is associated with a low-grade inflammation, but it is unknown how hyperandrogenism, the hallmark of PCOS, affects the immune system. Using a well-established PCOS-like mouse model, we demonstrate that androgen exposure affects immune cell populations in reproductive, metabolic, and immunological tissues differently in a site-specific manner. Co-treatment with flutamide, an androgen receptor antagonist, prevents most of these alterations, demonstrating that these effects are mediated through androgen receptor activation. Dihydrotestosterone (DHT)-exposed mice display a drastically reduced eosinophil population in uterus compared to controls, coupled with lower levels of eotaxin (CCL11), suggesting a reduced recruitment from blood. Decreased frequencies of eosinophils were also seen in visceral adipose tissue (VAT). A higher expression level of CD69, a marker of activation or tissue residency, was consistently found on natural killer (NK) cells in all analyzed tissues. However, a higher frequency of NK cells and elevated levels of IFN-γ and TNF-α were only seen in uteri of androgen-exposed mice, while NK cell frequencies were unaffected in all other analyzed compartments. Distinct alterations of macrophages in ovaries, uterus and VAT were also found in DHT-exposed mice and could potentially be linked to PCOS-like traits of the model. Indeed, androgen-exposed mice were insulin resistant and displayed an aberrant immune profile in VAT, albeit unaltered fat mass. Collectively, we demonstrate that hyperandrogenism causes tissue-specific alterations of immune cells in reproductive organs and VAT, which could have considerable implications on tissue function and contribute to the reduced fertility and metabolic comorbidities associated with PCOS.

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Section: Resultssupporting

confidence: 92%

Androgens modulate the immune profile in a mouse model of polycystic ovary syndrome

Torstensson,

Ascani,

Risal

et al. 2024

Preprint

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“…These PCOS-like mice have longer anogenital distance, are in a chronic diestrus phase, and have glucose intolerance (Xiong et al, 2022;Ascani et al, 2023). These effects are not present in DHT-exposed mice receiving the androgen receptor antagonist flutamide (Ascani et al, 2023). DHT-exposed PCOS mice had fewer type I muscle fibers compared to controls (Fig.…”

Section: Total Protein Expression and Phosphorylation In Skeletal Musclementioning

confidence: 88%

“…Then, an androgen-exposed PCOS-like mouse model was used to corroborate that androgen exposure leads to a shift in muscle fiber type. These PCOS-like mice have longer anogenital distance, are in a chronic diestrus phase, and have glucose intolerance (Xiong et al, 2022;Ascani et al, 2023). These effects are not present in DHT-exposed mice receiving the androgen receptor antagonist flutamide (Ascani et al, 2023).…”

Section: Total Protein Expression and Phosphorylation In Skeletal Musclementioning

confidence: 94%

“…Mice were maintained under standard housing (Fig. 1C) (Ascani et al, 2023). At 15-17 weeks of age, the mice were euthanized and gastrocnemius muscle tissue was dissected and snap-frozen.…”

Section: Mouse Study Protocol and Western Blot Analysismentioning

confidence: 99%

“…A subset of DHT-exposed wt mice received a slow-release flutamide pellet (n=5, 25 mg flutamide/pellet, 90-day release, Innovative Research of America, Sarasota, FL, USA) (Fig. 1C) (Ascani et al, 2023).…”

Section: Mouse Study Protocol and Western Blot Analysismentioning

confidence: 99%

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Proteomic analysis shows decreased Type I fibers and ectopic fat accumulation in skeletal muscle from women with PCOS

Stener-Victorin

Eriksson

Shresta

et al. 2023

Preprint

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Polycystic ovary syndromes (PCOS) main feature is hyperandrogenism, which is linked to a higher risk of metabolic disorders in women. Gene expression analyses in adipose tissue and skeletal muscle reveal dysregulated metabolic pathways in women with PCOS, but these differences do not necessarily lead to changes in protein levels and biological function. To advance our understanding of the molecular alterations in PCOS, we performed global proteomic and phosphorylation site analysis using tandem mass spectrometry. Adipose tissue and skeletal muscle were collected at baseline from 10 women with and without PCOS, and in women with PCOS after 5 weeks of treatment with electrical stimulation. Perilipin-1, a protein that typically coats the surface of lipid droplets in adipocytes, was increased whereas proteins involved in muscle contraction and type I muscle fiber function were downregulated in PCOS muscle. Proteins in the thick and thin filaments had many altered phosphorylation sites, indicating differential protein activity. The upregulated proteins in muscle post treatment were enriched in pathways involved in extracellular matrix organization and wound healing, which may reflect a protective adaptation to repeated contractions and tissue damage due to needling. A similar, albeit less pronounced, upregulation in extracellular matrix organization pathways was also seen in adipose tissue. Our results suggest that hyperandrogenic women with PCOS have higher levels of extramyocellular lipids, fewer oxidative and insulin-sensitive type I muscle fibers. These could be key factors leading insulin resistance in PCOS muscle while electric stimulation-induced tissue remodeling may be protective.

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Androgens Modulate the Immune Profile in a Mouse Model of Polycystic Ovary Syndrome

Torstensson,

Ascani,

Risal

et al. 2024

Advanced Science

View full text Add to dashboard Cite

Polycystic ovary syndrome (PCOS) is associated with a low‐grade inflammation, but it is unknown how hyperandrogenism, the hallmark of PCOS, affects the immune system. Using a PCOS‐like mouse model, it is demonstrated that hyperandrogenism affects immune cell populations in reproductive, metabolic, and immunological tissues differently in a site‐specific manner. Co‐treatment with an androgen receptor antagonist prevents most of these alterations, demonstrating that these effects are mediated through androgen receptor activation. Dihydrotestosterone (DHT)‐exposed mice displayed a drastically reduced eosinophil population in the uterus and visceral adipose tissue (VAT). A higher frequency of natural killer (NK) cells and elevated levels of IFN‐γ and TNF‐α are seen in uteri of androgen‐exposed mice, while NK cells in VAT and spleen displayed a higher expression level of CD69, a marker of activation or tissue residency. Distinct alterations of macrophages in the uterus, ovaries, and VAT are also found in DHT‐exposed mice and can potentially be linked to PCOS‐like traits of the model. Indeed, androgen‐exposed mice are insulin‐resistant, albeit unaltered fat mass. Collectively, it is demonstrated that hyperandrogenism causes tissue‐specific alterations of immune cells in reproductive organs and VAT, which can have considerable implications on tissue function and contribute to the reduced fertility and metabolic comorbidities associated with PCOS.

show abstract

The role of B cells in immune cell activation in polycystic ovary syndrome

Cited by 3 publications

References 54 publications

Androgens modulate the immune profile in a mouse model of polycystic ovary syndrome

Androgens modulate the immune profile in a mouse model of polycystic ovary syndrome

Proteomic analysis shows decreased Type I fibers and ectopic fat accumulation in skeletal muscle from women with PCOS

Androgens Modulate the Immune Profile in a Mouse Model of Polycystic Ovary Syndrome

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