| 1. |
- Ascani, Angelo, et al.
(författare)
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The role of B cells in immune cell activation in polycystic ovary syndrome.
- 2023
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Ingår i: eLife. - 2050-084X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Variations in B cell numbers are associated with polycystic ovary syndrome (PCOS) through unknown mechanisms. Here, we demonstrate that B cells are not central mediators of PCOS pathology and that their frequencies are altered as a direct effect of androgen receptor activation. Hyperandrogenic women with PCOS have increased frequencies of age-associated double-negative B memory cells and increased levels of circulating immunoglobulin M (IgM). However, the transfer of serum IgG from women into wild-type female mice induces only an increase in body weight. Furthermore, RAG1 knockout mice, which lack mature T- and B cells, fail to develop any PCOS-like phenotype. In wild-type mice, co-treatment with flutamide, an androgen receptor antagonist, prevents not only the development of a PCOS-like phenotype but also alterations of B cell frequencies induced by dihydrotestosterone (DHT). Finally, B cell-deficient mice, when exposed to DHT, are not protected from developing a PCOS-like phenotype. These results urge further studies on B cell functions and their effects on autoimmune comorbidities highly prevalent among women with PCOS.
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| 2. |
- Lu, Haojiang, et al.
(författare)
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Dissecting the Impact of Maternal Androgen Exposure on Developmental Programming through Targeting the Androgen Receptor
- 2024
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Ingår i: Advanced Science. - : John Wiley & Sons. - 2198-3844.
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Tidskriftsartikel (refereegranskat)abstract
- Women with polycystic ovary syndrome (PCOS) exhibit sustained elevation incirculating androgens during pregnancy, an independent risk factor linked topregnancy complications and adverse outcomes in offspring. Yet, furtherstudies are required to understand the effects of elevated androgens on celltype-specific placental dysfunction and fetal development. Therefore, aPCOS-like mouse model induced by continuous androgen exposure isexamined. The PCOS-mice exhibited impaired placental and embryonicdevelopment, resulting in mid-gestation lethality. Co-treatment with theandrogen receptor blocker, flutamide, prevents these phenotypes includinggerm cell specification . Comprehensive profiling of the placenta bywhole-genome bisulfite and RNA sequencing shows a reduced proportion oftrophoblast precursors, possibly due to the downregulation of Cdx2expression. Reduced expression of Gcm1, Synb, and Prl3b1 is associated withreduced syncytiotrophoblasts and sinusoidal trophoblast giant cells, impairsplacental labyrinth formation. Importantly, human trophoblast organoidsexposed to androgens exhibit analogous changes, showing impairedtrophoblast differentiation as a key feature in PCOS-related pregnancycomplications. These findings provide new insights into the potential cellulartargets for future treatments.
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| 3. |
- Risal, Sanjiv, et al.
(författare)
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Transgenerational transmission of reproductive and metabolic dysfunction in the male progeny of polycystic ovary syndrome
- 2023
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Ingår i: Cell Reports Medicine. - : Cell Press. - 2666-3791. ; 4:5
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Tidskriftsartikel (refereegranskat)abstract
- The transgenerational maternal effects of polycystic ovary syndrome (PCOS) in female progeny are being revealed. As there is evidence that a male equivalent of PCOS may exists, we ask whether sons born to mothers with PCOS (PCOS-sons) transmit reproductive and metabolic phenotypes to their male progeny. Here, in a register-based cohort and a clinical case-control study, we find that PCOS-sons are more often obese and dyslipidemic. Our prenatal androgenized PCOS-like mouse model with or without diet-induced obesity confirmed that reproductive and metabolic dysfunctions in first-generation (F1) male offspring are passed down to F3. Sequencing of F1–F3 sperm reveals distinct differentially expressed (DE) small non-coding RNAs (sncRNAs) across generations in each lineage. Notably, common targets between transgenerational DEsncRNAs in mouse sperm and in PCOS-sons serum indicate similar effects of maternal hyperandrogenism, strengthening the translational relevance and highlighting a previously underappreciated risk of transmission of reproductive and metabolic dysfunction via the male germline.
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