| 1. |
- Benrick, Anna, 1979, et al.
(författare)
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Electroacupuncture mimics exercise-induced changes in skeletal muscle gene expression in polycystic ovary syndrome women.
- 2020
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 105:6, s. 2027-2041
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Tidskriftsartikel (refereegranskat)abstract
- Autonomic nervous system activation mediates the increase in whole-body glucose uptake in response to electroacupuncture but the mechanisms are largely unknown.To identify the molecular mechanisms underlying electroacupuncture-induced glucose uptake in skeletal muscle in insulin-resistant overweight/obese women with and without polycystic ovary syndrome (PCOS).Participants: In a case-control study, skeletal muscle biopsies were collected from 15 women with PCOS and 14 controls before and after electroacupuncture. Gene expression and methylation was analyzed using Illumina BeadChips arrays.A single bout of electroacupuncture restores metabolic and transcriptional alterations and induces epigenetic changes in skeletal muscle. Transcriptomic analysis revealed 180 unique genes (q<0.05) whose expression was changed by electroacupuncture, with 95% of the changes towards a healthier phenotype. We identified DNA methylation changes at 304 unique sites (q<0.20), and these changes correlated with altered expression of 101 genes (p<0.05). Among the 50 most upregulated genes in response to electroacupuncture, 38% were also upregulated in response to exercise. We identified a subset of genes that were selectively altered by electroacupuncture in women with PCOS. For example, MSX1 and SRNX1 were decreased in muscle tissue of women with PCOS and were increased by electroacupuncture and exercise. siRNA-mediated silencing of these two genes in cultured myotubes decreased glycogen synthesis, supporting a role for these genes in glucose homeostasis.Our findings provide evidence that electroacupuncture normalizes gene expression in skeletal muscle in a manner similar to acute exercise. Electroacupuncture might therefore be a useful way of assisting those who have difficulties performing exercise.
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| 2. |
- Benrick, Anna, 1979-, et al.
(författare)
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Electroacupuncture mimics exercise-induced changes in skeletal muscle gene expression in women with polycystic ovary syndrome
- 2020
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 105:6, s. 2027-2041
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Tidskriftsartikel (refereegranskat)abstract
- ContextAutonomic nervous system activation mediates the increase in whole-body glucose uptake in response to electroacupuncture but the mechanisms are largely unknown.ObjectiveTo identify the molecular mechanisms underlying electroacupuncture-induced glucose uptake in skeletal muscle in insulin-resistant overweight/obese women with and without polycystic ovary syndrome (PCOS).Design/ParticipantsIn a case-control study, skeletal muscle biopsies were collected from 15 women with PCOS and 14 controls before and after electroacupuncture. Gene expression and methylation was analyzed using Illumina BeadChips arrays.ResultsA single bout of electroacupuncture restores metabolic and transcriptional alterations and induces epigenetic changes in skeletal muscle. Transcriptomic analysis revealed 180 unique genes (q < 0.05) whose expression was changed by electroacupuncture, with 95% of the changes towards a healthier phenotype. We identified DNA methylation changes at 304 unique sites (q < 0.20), and these changes correlated with altered expression of 101 genes (P < 0.05). Among the 50 most upregulated genes in response to electroacupuncture, 38% were also upregulated in response to exercise. We identified a subset of genes that were selectively altered by electroacupuncture in women with PCOS. For example, MSX1 and SRNX1 were decreased in muscle tissue of women with PCOS and were increased by electroacupuncture and exercise. siRNA-mediated silencing of these 2 genes in cultured myotubes decreased glycogen synthesis, supporting a role for these genes in glucose homeostasis.ConclusionOur findings provide evidence that electroacupuncture normalizes gene expression in skeletal muscle in a manner similar to acute exercise. Electroacupuncture might therefore be a useful way of assisting those who have difficulties performing exercise.
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| 3. |
- Kataoka, Josefin, et al.
(författare)
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Effects of weight loss intervention on anxiety, depression and quality of life in women with severe obesity and polycystic ovary syndrome
- 2024
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women that is associated with an increased risk of anxiety and depression and with a lower health-related quality of life (HRQoL). PCOS is closely associated with obesity, which per se can lead to symptoms of anxiety and depression and lower HRQoL. The first-line treatment for PCOS is weight loss through lifestyle intervention, which has been shown to improve all symptoms of the syndrome. The aim of this study was to investigate symptoms of anxiety and depression and HRQoL in women with severe obesity (BMI ≥ 35) with and without PCOS, and to evaluate the effect of a one-year structured weight loss intervention. A total of 246 women with severe obesity (PCOS n = 63, non-PCOS n = 183) were included. The comprehensive psychopathological rating scale self-rating scale for affective symptoms (CPRS-S-A) and the short form-36 (SF-36) were used to assess symptoms of anxiety and depression and HRQoL. In total 72 women of the 246 women with severe obesity completed a one-year weight loss programme and were followed up and compared with baseline data. In women with severe obesity, there were no differences in symptoms of anxiety and depression and HRQoL between women with and without PCOS at baseline. Clinically relevant anxiety symptoms were present in 71.3% (PCOS) and 65.6% (non-PCOS), and depression symptoms were present in 56.4% (PCOS) and 52.2% (non-PCOS). Significant weight loss improved physical HRQoL in all women, but reduced symptoms of anxiety and depression only in women without PCOS. There were no differences when comparing the changes between the groups. Women with severe obesity are severely affected by symptoms of anxiety and depression, independent of PCOS. Weight loss improved symptoms of anxiety and depression in women without PCOS, but there were no differences between groups in change from baseline to follow-up.Trial registration number: Clinical trial.gov: NCT01319162, March 18, 2011. Date of registration and enrolment of the first subject September 2011.
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| 4. |
- 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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| 5. |
- Risal, Sanjiv, et al.
(författare)
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Prenatal androgen exposure and transgenerational susceptibility to polycystic ovary syndrome
- 2019
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Ingår i: Nature Medicine. - : Nature Publishing Group. - 1078-8956 .- 1546-170X. ; 25:12, s. 1894-1904
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Tidskriftsartikel (refereegranskat)abstract
- How obesity and elevated androgen levels in women with polycystic ovary syndrome (PCOS) affect their offspring is unclear. In a Swedish nationwide register-based cohort and a clinical case-control study from Chile, we found that daughters of mothers with PCOS were more likely to be diagnosed with PCOS. Furthermore, female mice (F0) with PCOS-like traits induced by late-gestation injection of dihydrotestosterone, with and without obesity, produced female F1-F3 offspring with PCOS-like reproductive and metabolic phenotypes. Sequencing of single metaphase II oocytes from F1-F3 offspring revealed common and unique altered gene expression across all generations. Notably, four genes were also differentially expressed in serum samples from daughters in the case-control study and unrelated women with PCOS. Our findings provide evidence of transgenerational effects in female offspring of mothers with PCOS and identify possible candidate genes for the prediction of a PCOS phenotype in future generations.
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| 6. |
- 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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| 7. |
- Torstensson, Sara, et al.
(författare)
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Androgens Modulate the Immune Profile in a Mouse Model of Polycystic Ovary Syndrome
- 2024
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Ingår i: Advanced Science. - : John Wiley & Sons. - 2198-3844. ; 11:28
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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