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BMC Medicine Jun 2024Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive ages. Our previous study has implicated a possible link between RNA...
BACKGROUND
Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive ages. Our previous study has implicated a possible link between RNA editing and PCOS, yet the actual role of RNA editing, its association with clinical features, and the underlying mechanisms remain unclear.
METHODS
Ten RNA-Seq datasets containing 269 samples of multiple tissue types, including granulosa cells, T helper cells, placenta, oocyte, endometrial stromal cells, endometrium, and adipose tissues, were retrieved from public databases. Peripheral blood samples were collected from twelve PCOS and ten controls and subjected to RNA-Seq. Transcriptome-wide RNA-Seq data analysis was conducted to identify differential RNA editing (DRE) between PCOS and controls. The functional significance of DRE was evaluated by luciferase reporter assays and overexpression in human HEK293T cells. Dehydroepiandrosterone and lipopolysaccharide were used to stimulate human KGN granulosa cells to evaluate gene expression.
RESULTS
RNA editing dysregulations across multiple tissues were found to be associated with PCOS in public datasets. Peripheral blood transcriptome analysis revealed 798 DRE events associated with PCOS. Through weighted gene co-expression network analysis, our results revealed a set of hub DRE events in PCOS blood. A DRE event in the eukaryotic translation initiation factor 2-alpha kinase 2 (EIF2AK2:chr2:37,100,559) was associated with PCOS clinical features such as luteinizing hormone (LH) and the ratio of LH over follicle-stimulating hormone. Luciferase assays, overexpression, and knockout of RNA editing enzyme adenosine deaminase RNA specific (ADAR) showed that the ADAR-mediated editing cis-regulated EIF2AK2 expression. EIAF2AK2 showed a higher expression after dehydroepiandrosterone and lipopolysaccharide stimulation, triggering changes in the downstrean MAPK pathway.
CONCLUSIONS
Our study presented the first evidence of cross-tissue RNA editing dysregulation in PCOS and its clinical associations. The dysregulation of RNA editing mediated by ADAR and the disrupted target EIF2AK2 may contribute to PCOS development via the MPAK pathway, underlining such epigenetic mechanisms in the disease.
Topics: Humans; Polycystic Ovary Syndrome; Female; RNA Editing; eIF-2 Kinase; Adult; HEK293 Cells; Gene Expression Profiling; Clinical Relevance
PubMed: 38853264
DOI: 10.1186/s12916-024-03434-8 -
Scientific Reports Jun 2024The aim of the study was to investigate the relation between thyroid autoimmunity (TAI), reflected as the presence of thyroid peroxidase antibodies (TPOAb), and...
The aim of the study was to investigate the relation between thyroid autoimmunity (TAI), reflected as the presence of thyroid peroxidase antibodies (TPOAb), and parameters of ovarian reserve in women with type 1 diabetes (T1DM) and polycystic ovary syndrome (PCOS). We studied 83 euthyroid women with T1DM (age - 26 ± 5 years, BMI - 24 ± 3 kg/m) - 12 with PCOS and positive TPOAb (PCOS + TPOAb), 29 with PCOS with negative TPOAb (PCOS + noTPOAb), 18 without PCOS with positive TPOAb (noPCOS + TPOAb), 24 without PCOS with negative TPOAb (noPCOS + noTPOAb). Serum concentrations of anti-Müllerian hormone (AMH), sex hormones, TSH, thyroid hormones and TPOAb were assessed. The prevalence of TAI was comparable between PCOS and noPCOS. We did not observe differences in hormonal profile or AMH concentration between two PCOS groups-PCOS + TPOAb and PCOS + noTPOAb (p > 0.05). Women with PCOS + TPOAb had lower FSH concentration and higher LH/FSH index than noPCOS + noTPOAb (p = 0.027; p = 0.019, respectively). Moreover, PCOS + TPOAb had lower oestradiol level than noPCOS + TPOAb (p = 0.041). AMH concentration was higher in both groups with PCOS, independent of TPOAb presence, than in noPCOS + noTPOAb (both p < 0.001). The presence of positive TPOAb titre was not related to the studied parameters of ovarian reserve - AMH and ovarian follicle number. In multiple linear regression analysis, the only significant predictor of AMH in the whole studied group with T1DM was total daily insulin dose U/kg (β = - 0.264; p = 0.022). The presence of TAI did not affect the hormonal profile or ovarian reserve in women with T1DM with and without PCOS.
Topics: Humans; Female; Diabetes Mellitus, Type 1; Ovarian Reserve; Polycystic Ovary Syndrome; Adult; Autoimmunity; Thyroid Gland; Autoantibodies; Young Adult; Anti-Mullerian Hormone; Iodide Peroxidase
PubMed: 38851814
DOI: 10.1038/s41598-024-63741-1 -
Journal of Ovarian Research Jun 2024
PubMed: 38851746
DOI: 10.1186/s13048-024-01447-8 -
Archives of Dermatological Research Jun 2024Hidradenitis suppurativa (HS) is an inflammatory disorder of follicular biology; androgens are believed to be involved in its pathogenesis. Polycystic ovary syndrome...
Hidradenitis suppurativa (HS) is an inflammatory disorder of follicular biology; androgens are believed to be involved in its pathogenesis. Polycystic ovary syndrome (PCOS) is similarly characterized by hyperandrogenism. Previous studies have found a lasting association of HS and PCOS. Socioeconomic status (SES) has been described as a comorbidity for both HS and PCOS that has not been accounted for in prior studies; we sought to investigate this association while adjusting for this. We also analyzed the prevalence of PCOS among HS patients. Using the All of Us database, female HS patients were stratified by PCOS diagnosis and compared by age, race, and ethnicity. Female HS patients were also nearest-neighbor propensity-score matched to controls at a 4:1 ratio, selecting for race, ethnicity, age, ever smoker, alcohol use disorder, obesity, type II diabetes, Medicaid status, and community deprivation index. Univariable and multivariable logistic regression was conducted to estimate the effect of HS on the presence of PCOS. The distribution of race among HS patients with PCOS was significantly different than HS patients without PCOS. A total of 1,022 female HS patients and 4,088 matched female controls were included. Significantly more patients carried a diagnosis of PCOS compared to controls (8.8% versus 4.3%, p < .001). In multivariable logistic regression, PCOS was significantly associated with HS [OR 1.71 (95% CI 1.34-2.17)]. This is the first study investigating the association of HS and PCOS within the All of Us database. We found that females with HS had a 1.34- to 2.17-fold increased odds of having PCOS, which is consistent with previous analyses. However, our analysis, in addition to controlling for common medical co-morbidities found in both HS and PCOS, also accounts for markers of SES at an individual and community level, further strengthening the association of HS with PCOS.
Topics: Humans; Polycystic Ovary Syndrome; Female; Hidradenitis Suppurativa; Adult; Prevalence; United States; Young Adult; Middle Aged; Comorbidity; Adolescent; Social Class; Case-Control Studies
PubMed: 38850290
DOI: 10.1007/s00403-024-02971-9 -
Frontiers in Microbiology 2024Folliculogenesis and oligo/anovulation are common pathophysiological characteristics in polycystic ovary syndrome (PCOS) patients, and it is also accompanied by gut...
INTRODUCTION
Folliculogenesis and oligo/anovulation are common pathophysiological characteristics in polycystic ovary syndrome (PCOS) patients, and it is also accompanied by gut microbiota dysbiosis. It is known that physical activity has beneficial effects on improving metabolism and promoting ovulation and menstrual cycle disorder in PCOS patients, and it can also modulate the gastrointestinal microbiota in human beings. However, the mechanism remains vague. Irisin, a novel myokine, plays a positive role in the mediating effects of physical activity.
METHODS
Mice were randomly divided into the control group, PCOS group and PCOS+irisin group. PCOS model was induced by dehydroepiandrosterone (DHEA) and high-fat diet (HFD). The PCOS+irisin group was given irisin 400μg/kg intraperitoneal injection every other day for 21 days. The serum sex hormones were measured by radioimmunoassay. Hematoxylin and Eosin (H&E) Staining and immunohistochemistry (IHC) were conducted on ovarian tissue. The feces microbiota and metabolomic characteristics were collected by 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS).
RESULTS
In this study, we demonstrated that irisin supplementation alleviated reproductive endocrine disorders of PCOS mice, including estrous cycle disturbance, ovarian polycystic degeneration, and hyperandrogenemia. Irisin also improved the PCOS follicles dysplasia and ovulation disorders, while it had no significant effect on the quality of oocytes. Moreover, irisin could mitigate the decreased bacteria of Odoribacter and the increased bacteria of Eisenbergiella and Dubosiella in PCOS mice model. Moreover, irisin could alleviate the increased fecal metabolites: Methallenestril and PS (22:5(4Z,7Z,10Z,13Z,16Z)/ LTE4).
CONCLUSION
These results suggest that irisin may alleviate the status of PCOS mice model by modulating androgen-induced gut microbiota dysbiosis and fecal metabolites. Hence, our study provided evidence that irisin may be considered as a promising strategy for the treatment of PCOS.
PubMed: 38846566
DOI: 10.3389/fmicb.2024.1373077 -
Trials Jun 2024Women with polycystic ovary syndrome (PCOS) are usually selected to undergo an ovulation induction regimen or a programmed regimen for endometrial preparation in the...
BACKGROUND
Women with polycystic ovary syndrome (PCOS) are usually selected to undergo an ovulation induction regimen or a programmed regimen for endometrial preparation in the frozen-thawed embryo transfer (FET) during their IVF/ICSI treatment. The programmed regimen permits flexible scheduling of embryo transfer but requires long-term usage of exogenous estrogen and higher dosages of luteal support while the letrozole ovulation regimen needs lower dosages of luteal support only. Recently, multiple studies have shown that the letrozole ovulation regimen can improve pregnancy outcomes of FET in women with PCOS compared with the programmed regimen. However, most of these studies are retrospective, and prospective studies are urgently needed the evidence from the perspective study is insufficient.
METHODS/DESIGN
We are undertaking a multicentre, randomized, controlled clinical trial of an endometrial preparation regimen for FET in women with PCOS. The eligible women are randomly assigned to either the letrozole ovulation regimen or the programmed regimen for endometrial preparation. The primary outcome is the clinical pregnancy rate.
DISCUSSION
The results of this study will provide evidence for whether the letrozole ovulation regimen for endometrial preparation could improve pregnancy outcomes in PCOS women undergoing FET.
TRIAL REGISTRATION
Chinese Clinical Trial Registry ChiCTR2200062244. Registered on 31 July 2022.
Topics: Humans; Polycystic Ovary Syndrome; Female; Letrozole; Pregnancy; Embryo Transfer; Ovulation Induction; Randomized Controlled Trials as Topic; Multicenter Studies as Topic; Pregnancy Rate; Cryopreservation; Treatment Outcome; Fertility Agents, Female; Ovulation; China; Adult; Infertility, Female
PubMed: 38845035
DOI: 10.1186/s13063-024-08164-z -
Frontiers in Endocrinology 2024Previous observational studies have identified a correlation between elevated plasma homocysteine (Hcy) levels and polycystic ovary syndrome (PCOS). This study aimed to...
OBJECTIVE
Previous observational studies have identified a correlation between elevated plasma homocysteine (Hcy) levels and polycystic ovary syndrome (PCOS). This study aimed to determine whether a causal relationship exists between Hcy and PCOS at the genetic level.
METHODS
A two-sample Mendelian Randomization (TSMR) study was implemented to assess the genetic impact of plasma levels of Hcy, folate, vitamin B12, and vitamin B6 on PCOS in individuals of European ancestry. Independent single nucleotide polymorphisms (SNPs) associated with Hcy (n=12), folate (n=2), vitamin B12 (n=10), and vitamin B6 (n=1) at genome-wide significance levels (<5×10) were selected as instrumental variables (IVs). Data concerning PCOS were obtained from the Apollo database. The primary method of causal estimation was inverse variance weighting (IVW), complemented by sensitivity analyses to validate the results.
RESULTS
The study found no genetic evidence to suggest a causal association between plasma levels of Hcy, folate, vitamin B12, vitamin B6, and PCOS. The effect sizes, determined through random-effect IVW, were as follows: Hcy per standard deviation increase, OR = 1.117, 95%CI: (0.842, 1.483), = 0.442; folate per standard deviation increase, OR = 1.008, CI: (0.546, 1.860), = 0.981; vitamin B12 per standard deviation increase, OR = 0.978, CI: (0.808, 1.185), = 0.823; and vitamin B6 per standard deviation increase, OR = 0.967, CI: (0.925, 1.012), = 0.145. The fixed-effect IVW results for each nutrient exposure and PCOS were consistent with the random-effect IVW findings, with additional sensitivity analyses reinforcing these outcomes.
CONCLUSION
Our findings indicate no causal link between Hcy, folate, vitamin B12, vitamin B6 levels, and PCOS.
Topics: Humans; Polycystic Ovary Syndrome; Female; Mendelian Randomization Analysis; Homocysteine; Polymorphism, Single Nucleotide; Vitamin B Complex; Folic Acid; Vitamin B 12; Genome-Wide Association Study; Vitamin B 6; Adult
PubMed: 38841299
DOI: 10.3389/fendo.2024.1393847 -
Journal of Ovarian Research Jun 2024Polycystic Ovary Syndrome (PCOS) is a widespread endocrine disorder among women, characterized by symptoms like ovarian cysts, hormonal imbalance, and metabolic issues....
Enhancing angiogenesis and inhibiting apoptosis: evaluating the therapeutic efficacy of bone marrow mesenchymal stem cell-derived exosomes in a DHEA-induced PCOS mouse model.
BACKGROUND
Polycystic Ovary Syndrome (PCOS) is a widespread endocrine disorder among women, characterized by symptoms like ovarian cysts, hormonal imbalance, and metabolic issues. This research evaluates the therapeutic potential of Bone Marrow Mesenchymal Stem Cell-derived exosomes (BMSC-Exo) in treating PCOS symptoms within a mouse model.
METHODS
BMSC-Exo were isolated from NMRI mice, characterized using Transmission Electron Microscopy (TEM) and Nanoparticle Tracking Analysis (NTA), and administered to a PCOS mouse model induced by dehydroepiandrosterone (DHEA). The efficacy of BMSC-Exo was assessed in three groups of mice: a control group, a PCOS group, and a PCOS group treated with intravenous BMSC-Exo. Morphological changes in ovarian tissue were examined by Hematoxylin and Eosin (H&E) staining, apoptosis was determined using the TUNEL assay, and CD31 expression was analyzed through immunofluorescent staining to assess angiogenic activity.
RESULTS
The existence of BMSCs-Exo was confirmed via TEM and NTA, revealing their distinct cup-shaped morphology and a size range of 30 to 150 nanometers. H&E staining revealed that BMSCs-Exo treatment improved ovarian morphology in PCOS models, increasing corpora lutea and revitalizing granulosa cell layers, suggesting a reversal of PCOS-induced damage. TUNEL assays showed that BMSCs-Exo treatment significantly reduced apoptosis in PCOS-affected ovarian cells to levels comparable with the control group, highlighting its role in mitigating PCOS-induced cellular apoptosis. Immunofluorescence for CD31 indicated that BMSCs-Exo treatment normalized endothelial marker expression and angiogenic activity in PCOS models, suggesting its effectiveness in modulating the vascular irregularities of PCOS. Collectively, these findings demonstrate the therapeutic potential of BMSCs-Exo in addressing ovarian dysfunction, cellular apoptosis, and aberrant angiogenesis associated with PCOS.
CONCLUSION
The study substantiates the role of BMSC-Exo in mitigating the deleterious effects of PCOS on ovarian tissue, with implications for enhanced follicular development and reduced cellular stress. The modulation of CD31 by BMSC-Exo further highlights their potential in normalizing PCOS-induced vascular anomalies. These findings propel the need for clinical investigations to explore BMSC-Exo as a promising therapeutic avenue for PCOS management.
Topics: Animals; Female; Polycystic Ovary Syndrome; Exosomes; Apoptosis; Dehydroepiandrosterone; Mice; Disease Models, Animal; Mesenchymal Stem Cells; Neovascularization, Physiologic; Ovary; Angiogenesis
PubMed: 38840218
DOI: 10.1186/s13048-024-01445-w -
Gynecological Endocrinology : the... Dec 2024Polycystic ovary syndrome (PCOS) and subclinical hypothyroidism (SCH) are prevalent gynecological conditions. However, the interrelationship between the two remains...
OBJECTIVES
Polycystic ovary syndrome (PCOS) and subclinical hypothyroidism (SCH) are prevalent gynecological conditions. However, the interrelationship between the two remains elusive. This study aims to elucidate the association between these conditions and determine the potential impact of SCH on the physiological and metabolic characteristics of patients with PCOS.
METHODS
This cross-sectional study enrolled 133 patients with PCOS from our Hospital. Participants were categorized into two groups: those with PCOS + SCH ( = 58) and those with PCOS ( = 75). Serum hormonal levels, metabolic markers, ovarian volume, and follicle count were compared between the groups.
RESULTS
There was a significant difference in BMI between the two groups, with a higher prevalence of obesity in the PCOS + SCH group ( = .014). Compared to the PCOS group, patients with PCOS + SCH had significantly higher levels of TSH ( < .001), triglycerides ( = .025), and HOMA-IR ( < .001), while LH levels were significantly lower ( = .048). However, multivariate linear regression analysis revealed that TSH, triglycerides, LH, and HOMA-IR were not determinants for the occurrence of SCH in patients with PCOS. Additionally, there was a notable reduction in follicle count in the left ovary for the PCOS + SCH group compared to the PCOS group ( = .003), and the overall follicle diameter of the PCOS + SCH group was also smaller ( = .010).
CONCLUSION
SCH may exert effects on the physiological and metabolic profiles of patients with PCOS. Further investigation into the relationship between these disorders is warranted to delineate their clinical implications.
Topics: Humans; Polycystic Ovary Syndrome; Female; Hypothyroidism; Cross-Sectional Studies; Adult; Ovary; Young Adult; Thyrotropin; Insulin Resistance; Luteinizing Hormone; Body Mass Index; Triglycerides; Ovarian Follicle
PubMed: 38835150
DOI: 10.1080/09513590.2024.2358219 -
PeerJ 2024To investigate the effect of GnRH agonist (GnRH-a) down-regulation prior to hormone replacement treatment (HRT) to prepare the endometrium in frozen embryo transfer...
Effect of GnRH agonist down-regulation combined with hormone replacement treatment on reproductive outcomes of frozen blastocyst transfer cycles in women of different ages.
OBJECTIVE
To investigate the effect of GnRH agonist (GnRH-a) down-regulation prior to hormone replacement treatment (HRT) to prepare the endometrium in frozen embryo transfer (FET) cycles in women of different ages.
METHODS
This was a retrospective study, and after excluding patients with adenomyosis, endometriosis, severe endometrial adhesions, polycystic ovary syndrome (PCOS), and repeated embryo implantation failures, a total of 4,091 HRT cycles were collected. Patients were divided into group A (<35 years old) and group B (≥35 years old), and each group was further divided into HRT and GnRHa-HRT groups. The clinical outcomes were compared between groups.
RESULTS
There was no statistically significant difference in clinical outcomes between the HRT and GnRHa-HRT groups among women aged <35 years. In women of advanced age, higher rates of clinical pregnancy and live birth were seen in the GnRHa-HRT group. Logistic regression analysis showed that female age and number of embryos transferred influenced the live birth rate in FET cycles, and in women aged ≥ 35 years, the use of GnRH-a down-regulation prior to HRT improved pregnancy outcomes.
CONCLUSIONS
In elderly woman without adenomyosis, endometriosis, PCOS, severe uterine adhesions, and RIF, hormone replacement treatment with GnRH agonist for pituitary suppression can improve the live birth rate of FET cycles.
Topics: Humans; Female; Embryo Transfer; Retrospective Studies; Adult; Gonadotropin-Releasing Hormone; Pregnancy; Down-Regulation; Hormone Replacement Therapy; Age Factors; Pregnancy Outcome; Pregnancy Rate; Embryo Implantation
PubMed: 38832029
DOI: 10.7717/peerj.17447