scholarly journals The Role of Microglia in the Polycystic Ovary Syndrome (PCOS)-Like Brain

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A556-A556
Author(s):  
Aisha Sati ◽  
Melanie Prescott ◽  
Christine Louise Jasoni ◽  
Elodie Desroziers ◽  
Rebecca Elaine Campbell

Abstract Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility, affecting roughly 1 in 8 women of reproductive age. Accumulating evidence from animal models suggests that the brain plays a key role in the development and maintenance of PCOS. In a well-characterised prenatally androgenised (PNA) mouse model of PCOS, aberrant neuronal wiring associated with PCOS deficits in adulthood are detected as early as postnatal day (P) 25, prior to disease onset. However, the mechanisms by which prenatal androgen exposure alters brain wiring remains unknown. Microglia, the immune cells of the brain, are active sculptors of neuronal wiring across development, mediating both the formation and removal of neuronal inputs. Therefore, microglia may play an important role in driving the abnormal neuronal wiring that leads to PCOS-like features in the PNA brain. Here, to assess whether microglia are altered in the brain of PNA mice, microglia number and morphology-associated activation states were quantified in two hypothalamic regions implicated in fertility regulation. Microglia were identified by immunolabelling for the microglia-specific marker, Iba-1, across developmental timepoints, including embryonic day 17.5, P0, P25, P40 and P60 (n = 7–14/group). At P0, PNA mice had significantly fewer “activated” amoeboid microglia compared to controls (P < 0.05). Later in development at P25, PNA mice exhibited significantly fewer “sculpting” microglia (P < 0.001), whereas at P60, PNA mice possessed a greater number of “activated” amoeboid microglia relative to controls (P < 0.01). This study demonstrates time-specific changes in the number and morphology of microglia in a mouse model of PCOS and suggests a role for microglia in driving the brain wiring abnormalities associated with PCOS. These findings support the need for future functional experiments to determine the relative importance of microglia function in shaping the PCOS-like brain and associated reproductive dysfunction.

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Madeleine J Cox ◽  
Melissa C Edwards ◽  
Ali Aflatounian ◽  
Valentina Rodriguez Paris ◽  
William L Ledger ◽  
...  

Abstract Polycystic ovary syndrome (PCOS) is a complex disorder characterised by endocrine, reproductive and metabolic abnormalities. Despite PCOS being the most common endocrinopathy affecting women of reproductive age, its etiology is poorly understood so there is no cure and symptom-oriented treatment is suboptimal. Elucidation of the underlying mechanisms involved in the pathogenesis of PCOS would pave the way for the development of new interventions for PCOS. Hyperandrogenism is the most consistent feature observed in PCOS patients, and recently aberrant neuroendocrine signalling and adipose tissue function have been proposed as playing a pathogenic role in the development of experimental PCOS. To investigate the role of adipose tissue and the brain as potential key sites for androgen receptor (AR)-mediated development of PCOS, we combined an adipocyte and brain-specific ARKO knockout (AdBARKO) mouse model with a dihydrotestosterone (DHT)-induced mouse model of PCOS. Wildtype (WT) and AdBARKO prepubertal mice were implanted with a blank or DHT implant and examined after 12 weeks. In WT control females, DHT exposure induced the PCOS reproductive traits of cycle irregularity, ovulatory dysfunction and reduced follicle health. In contrast, these reproductive features of PCOS were absent in DHT-treated AdBARKO females. The PCOS metabolic characteristics of increased adiposity, adipocyte hypertrophy and hepatic steatosis were induced by DHT in WT females. Despite DHT treatment, AdBARKO females displayed normal white adipose tissue weight, and adipocyte hypertrophy and hepatic steatosis were not evident. However, as with WT mice, DHT treatment induced increased fasting glucose levels in AdBARKO females. These results demonstrate that adipose tissue and the brain are key loci for androgen-mediated actions involved in the developmental origins of PCOS. These findings support targeting adipocyte and neuroendocrine AR-driven pathways in the future development of novel therapeutic strategies for PCOS.


2020 ◽  
Vol 16 ◽  
Author(s):  
Antonio Schiattarella ◽  
Gaetano Riemma ◽  
Marco La Verde ◽  
Gianluigi Franci ◽  
Annalisa Chianese ◽  
...  

: Polycystic ovary syndrome (PCOS) is a condition that affects about 15% of women of reproductive age and is correlated with infertility, insulin resistance, and obesity. The etiology of PCOS is multifactorial and genetic, endocrine, and metabolic causes were involved. New evidence suggests a link between microorganisms residing in the digestive tracts of humans and the development of PCOS. Moreover, an imbalance in the gut microbial community could be a possible factor for the onset of insulin resistance and obesity. Hyperandrogenism, a key feature of PCOS, could also play a critical role in shaping the microbiome community. Probiotics could modify the gut microbiota and serve as a potential treatment for PCOS. Here we disclose the association between PCOS and intestinal microbiota and the possible role of probiotics as a new treatment approach.


Author(s):  
Carrie Riestenberg ◽  
Anika Jagasia ◽  
Daniela Markovic ◽  
Richard P Buyalos ◽  
Ricardo Azziz

Abstract Context Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of reproductive-aged women, affecting approximately 5-20% of women of reproductive age. A previous estimate noted that the economic burden of PCOS approximates $3.7 billion annually in 2020 USD when considering only the costs of the initial diagnosis and of reproductive endocrine morbidities, not considering the costs of pregnancy-related and long-term morbidities. Objective To estimate the excess prevalence and economic burden of pregnancy-related and long-term health morbidities attributable to PCOS. Data Sources PubMed, EmBase and Cochrane Library. Study Selection Studies in which the diagnosis of PCOS was consistent with the Rotterdam, National Institutes of Health (NIH), or Androgen Excess & PCOS (AE-PCOS) Society criteria, or that used electronic medical record diagnosis codes, or diagnosis based on histopathologic sampling were eligible for inclusion. Studies that included an outcome of interest and a control group of non-PCOS patients who were matched or controlled for body mass index (BMI) were included. Data Extraction Two investigators working independently extracted data on study characteristics and outcomes. Data Synthesis Data was pooled using random-effects meta-analysis. The I 2statistic was used to assess inter-study heterogeneity. The quality of selected studies was assessed using the Newcastle-Ottawa Scale. Results The additional total healthcare-related economic burden due to pregnancy-related and long-term morbidities associated with PCOS in the United States is estimated to be $4.3 billion annually in 2020 USD. Conclusions Together with our prior analysis, the economic burden of PCOS is estimated at $8 billion annually in 2020 USD.


2021 ◽  
Author(s):  
Olga Glavnova ◽  
Ludmila Velikanova ◽  
Natalia Vorokhobina ◽  
raviliy Galakhova ◽  
Ekaterina Malevanania ◽  
...  

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Hassan Kahal ◽  
Stephen L. Atkin ◽  
Thozhukat Sathyapalan

Polycystic ovary syndrome (PCOS) is a common disorder affecting women of reproductive age and it is associated with increased cardiovascular risk. Obesity plays an important role in the pathogenesis of PCOS, and the majority of patients with PCOS are obese. Over the last 20 years, the prevalence of obesity has dramatically increased, with probable associated increase in PCOS. Weight reduction plays an integral part in the management of women with PCOS. In this paper, current available weight reduction therapies in the management of PCOS are discussed.


Author(s):  
Rooplekha Chauhan ◽  
Sonal Sahani ◽  
Ankita Garg

Background: Polycystic ovary syndrome (PCOS) is enigma faced by young females since the onset of urbanization. As on day, PCOS is the most common endocrine disorder in the women of reproductive age affecting 4-10%. This study done to measure serum vitamin D3 levels of PCOS patients and to identify its association with factors associated with various symptoms and signs in PCOS.Methods: Institutional based prospective observational study conducted on 70 patients of PCOS, both suspected and already diagnosed, attending gynecology OPD of Department of obstetrics and gynecology of NSCB Medical College Jabalpur from 1 March 2015 to 31 August 2016. Diagnosis of PCOS was made by Rotterdam 2003 criteria. A detailed assessment was done and preformed proforma was filled. Serum Vitamin D3 levels were estimated by standard lab technique ‘Liquid Chromatography Tandem Mass Spectrometry’ and categorized into vitamin D3 sufficient >30ng/dl, insufficient 20-29ng/dl and deficient <20ng/dl. Categorical data was coded numerically before the analysis. For comparison of frequency distribution chi square test or fisher’s exact test were applied as appropriate.Results: Prevalence of Vitamin D3 deficiency in patients of PCOS was found to be 84.3%.Conclusions: The present study concludes that there is correlation between vitamin D3 and PCOS, screening and correction of vitamin D3 deficiency may prevent PCOS and its manifestations. Hence, it is speculated that improvement of vitamin D3 levels at a younger age can contribute to prevention of PCOS.


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