Serum testosterone acts as a prognostic indicator in polycystic ovary syndrome-associated kidney injury.
ABSTRACT: Polycystic ovary syndrome (PCOS) is closely related with the onset and development of metabolic abnormalities. However, the correlation between PCOS and kidney injury has not been clarified, and the underlying mechanism remains unknown. Herein, we performed a prospective survey in 55 PCOS and 69 healthy participants. Furthermore, the correlation analyses between serum testosterone and renal functional manifestations of patients and healthy subjects, including urinary albumin to creatinine ratio (UACR), urinary κ-light chains (KapU), urinary λ-light chains (LamU), urinary α1-microglobulin (α1-MU), and urinary β2-microglobulin (β2-MU), were analyzed. Compared with that in normal subjects, the levels of serum testosterone and UACR were significantly higher in PCOS patients. Serum testosterone is significantly correlated with the disease severity of PCOS. Although urinary excretions of KapU, LamU, α1-MU, and β2-MU did not increase in PCOS patients, they had a significantly positive correlation with the extent of serum testosterone in PCOS patients. IN vitro, primary cultured human ovary granulosa cells (GCs) were isolated from the follicular fluid (FF) extracting from PCOS patients and controls. FF, especially which extracted from PCOS patients with a high expression of serum testosterone, significantly induced cell apoptosis and inflammation in human GCs. To examine the communication between PCOS and kidney injury, a human proximal tubular epithelial cell line (HKC-8) was cultured and administered FF. Interestingly, FF from PCOS patients with a higher level of serum testosterone induced fibrotic lesions in HKC-8 cells. These data suggest serum testosterone plays a critical role in PCOS and PCOS-associated kidney injury. Serum testosterone may serve as a promising indicator for kidney fibrotic injury outcomes in PCOS patients.
Project description:BACKGROUND:A retrospective case-control study was performed to evaluate whether PCOS-specific serum markers would change in women with polycystic ovary syndrome (PCOS) during the course of two consecutive cycles of clomiphene citrate (CC)-stimulation, which did not lead to a pregnancy. METHODS:Anovulatory PCOS patients who underwent two consecutive CC-cycles (n = 41) and anovulatory PCOS controls who chose an observational approach for two months (n = 24) were included in the study. The main outcome measures were levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), anti-Mullerian hormone (AMH), total testosterone, androstenedione, and sexual hormone binding globulin (SHBG). RESULTS:In the control group, PCOS-specific serum parameters did not change during two months (p > 0.05). In the CC-group, there were decreases in LH (11.8 ± 4.9 mU/mL vs. 10.9 ± 4.0 mU/mL; p = 0.029), the LH:FSH ratio (2.1 ± 0.8 mU/mL vs. 1.8 ± 0.5 mU/mL; p = 0.007), and AMH (8.08 ± 4.27 ng/mL vs. 7.17 ± 3.37 ng/mL; p = 0.011), as well as an increase in SHBG (46.0 ± 20.2 nmol/L vs. 51.2 ± 21.0 nmol/L; p < 0.001). A higher age and lower baseline total testosterone and AMH levels were predictive of an AMH decline (p < 0.05). CONCLUSION:Two cycles of CC-stimulation that did not lead to a pregnancy were accompanied by mean LH, AMH, and LH:FSH ratio declines and an SHBG increase. The clinical significance seems of minor relevance.
Project description:BACKGROUND:Fibroblast growth factor 13 (FGF13) is one of the most highly expressed FGF family members in adult mouse ovary. However, its precise roles in ovarian function remain largely unknown. We sought to evaluate the associations between FGF13 in follicular fluid and oocyte developmental competence in patients with polycystic ovary syndrome (PCOS). METHODS:A cross-sectional study was conducted on 43 patients with PCOS and 32 non-PCOS patients who underwent in vitro fertilization/intracytoplasmic sperm injection treatments. The highest quartiles of follicular fluid (FF)-FGF13 (?117.51 pg/mL) and FF-total testosterone (FF-TT) (?51.90 nmol/L) were defined as "elevated" FF-FGF13 levels and "elevated" FF-TT levels, respectively. RESULTS:The levels of FF-FGF13 were skewed, with a median of 82.97 pg/mL (59.79-117.51 pg/mL) in 75 patients. The prevalence of elevated FF-TT levels was significantly higher in the PCOS patients with elevated FF-FGF13 levels than in those without (64.3% vs. 35.7%, adjusted P?=?0.0096). FF-TT and increased ovarian volume (>?10 mL for one or both ovaries) were positively correlated with FF-FGF13 in PCOS patients (r?=?0.37, P?=?0.013; r?=?0.33, P?=?0.032). A negative association was evident between FF-FGF13 and the MII oocyte rate in the multiple linear regression analysis (??=?-?0.10, SE?=?0.045, adjusted P?=?0.027). However, the associations were not evident in the non-PCOS patients. CONCLUSIONS:Our study suggests the presence of intrafollicular FGF13 in PCOS patients and implies that FGF13 might be involved in the pathophysiological process of PCOS.
Project description:The heterogeneous and multifactorial essence of polycystic ovary syndrome (PCOS) renders a remarkable significance to microRNAs (miRNAs). Normo-androgenic (NA) and hyperandrogenic (HA) PCOS patients were compared with matched healthy women. Expression of miRNAs and TGF? signaling genes was studied by qRT-PCR and western blotting. Effect of androgen on expression of miR-93 and miR-21 and involvement of androgen receptor were appraised. In granulosa cells (GCs), miR-93 and miR-21 showed significantly increased levels in HA patients compared to NA patients. On the contrary, follicular fluid (FF) levels of both miRNAs were significantly decreased in HA group compared to control women. No significant change in the expression of miRNAs in serum samples was detected. Furthermore, mRNA levels of SMAD7 and TGFBR2 were significantly downregulated in GCs of HA group compared to NA and control subjects. TGFBR2 protein level was significantly decreased in HA patients compared to controls. Free testosterone and free androgen index were positively correlated with expression of miR-93 and miR-21 in GCs of PCOS group. Our findings show distinct molecular signature of different subtypes of PCOS. Intermediary position of miRNAs as androgen responsive factors may play critical role in the pathogenesis of PCOS in hyperandrogenic condition.
Project description:Oxidative stress (OS) is associated with poor oocyte quality and in vitro fertilization and embryo transfer (IVF-ET) outcomes for patients with polycystic ovary syndrome (PCOS). Growth hormone (GH) can function to reduce OS in some types of cells. Therefore, this prospective randomized study investigated whether GH can significantly improve OS and oocyte quality in women with PCOS. This study enrolled 109 and 50 patients with and without PCOS (controls), respectively. The patients with PCOS were randomly assigned to receive treatment with GH (PCOS-T) or not (PCOS-C). The primary outcome included markers of OS in serum and FF, and secondary outcomes were mitochondrial function in granulosa cells (GCs) and IVF-ET outcomes. The PCOS groups showed higher basal serum total oxidant status (TOS) and OS index (OSI) levels. The follicle fluid (FF) TOS and OSI and GC apoptosis rate were significantly higher, whereas the GC mitochondrial membrane potential (MMP) was significantly lower in the PCOS-C group than in the PCOS-T and non-PCOS control groups (P?<?0.05). Significantly more oocytes were fertilised and cleavage stage embryos were produced in the PCOS-T group than in the PCOS-C group (P?<?0.05). GH also improved the rates of implantation and clinical pregnancy, but not significantly (P?>?0.05). This study showed that GH alleviated the TOS and OSI level in FF and improved GC mitochondrial dysfunction and oocyte quality in patients with PCOS.Clinical Trial Registration Number: This project was prospectively registered on the Chinese Clinical Trial Registry on October 20, 2018. (ChiCTR1800019437) ( https://www.chictr.org.cn/edit.aspx?pid=28663&htm=4 ).
Project description:Polycystic ovary syndrome (PCOS), a common female endocrinopathy, is a complex metabolic syndrome of enhanced weight gain. The goal of this pilot study was to evaluate metabolic differences between normal (n=10) and PCOS (n=10) women via breath carbon isotope ratio, urinary nitrogen and nuclear magnetic resonance (NMR)-determined serum metabolites. Breath carbon stable isotopes measured by cavity ring down spectroscopy (CRDS) indicated diminished (p<0.030) lipid use as a metabolic substrate during overnight fasting in PCOS compared to normal women. Accompanying urinary analyses showed a trending correlation (p<0.057) between overnight total nitrogen and circulating testosterone in PCOS women, alone. Serum analyzed by NMR spectroscopy following overnight, fast and at 2 h following an oral glucose tolerance test showed that a transient elevation in blood glucose levels decreased circulating levels of lipid, glucose and amino acid metabolic intermediates (acetone, 2-oxocaporate, 2-aminobutyrate, pyruvate, formate, and sarcosine) in PCOS women, whereas the 2 h glucose challenge led to increases in the same intermediates in normal women. These pilot data suggest that PCOS-related inflexibility in fasting-related switching between lipid and carbohydrate/protein utilization for carbon metabolism may contribute to enhanced weight gain.
Project description:Context: Polycystic ovarian syndrome (PCOS), the most common endocrine disorder of reproductive- aged women, is associated with systemic low-grade inflammation. Objective: We propose that increased or altered intrafollicular inflammatory reactions also occur in periovulatory follicles of PCOS patients. Design: Gene profiling and quantitative PCR (qPCR) analyses in granulosa-lutein cells (GCs) collected from PCOS and non-PCOS women undergoing in vitro fertilization were compared with serum and follicular fluid (FF) levels of cytokines and chemokines. Setting: This was a university-based study. Patients: Twenty-one PCOS and 45 control patients were recruited: demographic, hormone, body mass index, and pregnancy outcomes were abstracted from patient data files. Interventions:GCcytokine/chemokinemRNAswere identified and analyzed by gene-chip microarrays/ qPCR before and after culture withhumanchorionic gonadotropin, DHT, IL-6, or IL-8; serum/FF cytokine levels were also analyzed. Main Outcome Measures: Relative serum/FF cytokine levels and GC cytokine expression before and after culture were compared and related to body mass index. Results: The following results were found: 1) PCOS GCs express elevated transcripts encoding cytokines, chemokines, and immune cell markers, 2) based on gene profiling and qPCR analyses, obese PCOS patients define a distinct PCOS disease subtype with the most dramatic increases in proinflammatory and immune-related factors, and 3) human chorionic gonadotropin and DHT increased cytokine production in cultured GCs, whereas cytokines augmented cytokine and vascular genes, indicating that hyperandrogenism/elevated LH and obesity in PCOS women augment intrafollicular cytokine production. Conclusions: Intrafollicular androgens and cytokines likely comprise a local regulatory loop that impacts GC expression of cytokines and chemokines and the presence of immune cells; this loop is further enhanced in the obese PCOS subtype. Overall design: A direct comparison of human granulosa cells from six different pooled sample groups that were distinct for PCOS status, BMI, and cytokine profile.
Project description:Background: Recent reports have highlighted the role of monosaccharide biosynthesis in the pathogenesis of polycystic ovary syndrome (PCOS), suggesting that these processes may serve as a biomarker in PCOS. Mannose is the main monosaccharide for protein glycosylation in mammals; however, the correlation between mannose and PCOS remains largely unknown. Materials and Methods: A total of 132 Chinese Han women were recruited at Shengjing Hospital of China Medical University. Mannose levels were measured in serum samples collected from 71 patients with PCOS (29 lean, 42 obese) and 61 control subjects (28 lean, 33 obese). Receiver operating characteristics (ROC) curves were prepared to compare the diagnostic performance of mannose and hormonal parameters, individually or in combination. Multivariate logistic regression analysis was used to assess whether serum mannose levels were associated with PCOS after adjusting for other co-variables. Results: We showed that serum mannose levels were significantly increased in PCOS patients compared with control subjects regardless of obese status, and hyperandrogenic PCOS patients had higher serum mannose levels than normo-androgenic PCOS and control subjects. In addition, serum mannose levels were significantly correlated with serum androgen levels. Mannose had an area under the curve (AUC) of 73% at a cutoff value of 225.79 ng/mL with a sensitivity of 66.2% and specificity of 73.8% for predicting PCOS. There were no differences between mannose, total testosterone, free testosterone, or dehydroepiandrosterone sulfate in the reliability of predicting PCOS using the method outlined by Hanley and McNeil. Combining mannose and total testosterone resulted in a higher AUC of 83.3%, and had moderate sensitivity (78.9%) and specificity (77%) for predicting PCOS. The positive and negative predictive values were 80% and 75.8%, respectively. Multivariate logistic regression revealed that higher serum mannose levels were strongly associated with an increased risk of PCOS (P = 0.016; odds ratio, 5.623; 95% confidence interval, 1.371-23.070). Conclusion: Taken together, substantially elevated serum mannose levels are significantly associated with PCOS, highlighting the importance of further research into the role of mannose in the pathogenesis of PCOS.
Project description:The purpose of the study was to investigate changes in adiponectin system expression in granulosa cells (GCs) and high molecular weight adiponectin levels in serum and follicular fluid (FF) of 40 women with polycystic ovary syndrome (PCOS) compared to those in 40 women with normal ovary function.Adiponectin (Adipo), adiponectin receptor 1 (AdipoR1), and adiponectin receptor 2 (AdipoR2) messenger RNA (mRNA) expression levels were measured using quantitative real-time polymerase chain reaction (qRT-PCR). High molecular weight (HMW) adiponectin protein concentration was evaluated by ELISA method. Data were analyzed using Student's t test and one-way ANOVA in SPSS 21 software. At oocyte retrieval, FF was aspirated and GCs were obtained from a pooled collection of FF per each patient.PCR results showed expression of adiponectin, AdipoR1, AdipoR2, follicle-stimulating hormone receptor (FSHR), and luteinizing hormone receptor (LHR) in GCs. After controlling body mass index (BMI) values, qRT-PCR demonstrated a decreased expression of adiponectin system in GCs of PCOS patients compared to those in controls (p?=?0.001). There was a strong positive correlation among AdipoR1 and AdipoR2 expression and also among FSH and LH receptor expression. (Both r?=?0.8, p?=?0.001). There were low levels of high molecular weight adiponectin in the serum of PCOS patients with controlled ovarian hyperstimulation (30.19?±?4.3 ng/ml) compared to the controls (48.47?±?5.9 ng/ml) and in the FF of PCOS patients with controlled ovarian hyperstimulation (7.86?±?1.44 ng/ml) compared to the controls (14.22?±?2.01 ng/ml; p?=?0.02).Lower expression of adiponectin and its receptors in GCs might be an important manifestation in gonadotropin-stimulated PCOS patients which could influence the physiologic adiponectin roles such as interaction with insulin and LH in induction of GC gene expression.
Project description:Patients diagnosed with polycystic ovary syndrome (PCOS) are at high risk of developing a myriad of endocrinologic and metabolic derailments. Moreover, PCOS is a leading cause of habitual abortion, also known as recurrent pregnancy loss (RPL). Meteorin-like protein (Metrnl) is a newly discovered adipokine with the potential to counteract the metaflammation. This study aimed at determining the associations of serum Metrnl levels with homocysteine, hs-CRP, and some components of metabolic syndrome in PCOS-RPL and infertile PCOS patients.This case-control study was conducted in 120 PCOS patients (60 PCOS-RPL and 60 infertile) and 60 control. Serum hs-CRP and homocysteine were assessed using commercial kits, while adiponectin, Metrnl, FSH, LH, free testosterone and insulin levels were analyzed using ELISA technique. Serum Metrnl levels were found to be lower in PCOS patients when compared to controls (67.98 ± 26.66 vs. 96.47 ± 28.72 pg/mL, P <0.001)). Furthermore, serum adiponectin levels were lower, while free testosterone, fasting insulin, HOMA-IR, homocysteine, and hs-CRP were significantly higher in PCOS group compared to controls. Moreover, serum Metrnl correlated with BMI, adiponectin, and homocysteine in controls, and inversely correlated with FBG, fasting insulin, and HOMA-IR in PCOS group and subgroups. Besides, it inversely correlated with hs-CRP in control, and PCOS group and subgroups. These findings revealed a possible role of Metrnl in the pathogenesis of PCOS and RPL. Nevertheless, there is a necessity for future studies to prove this concept.
Project description:Polycystic ovary syndrome (PCOS) remains one of the most common endocrine disorder in premenopausal women with an unfavorable metabolic risk profile. Here, we investigate whether biochemical hyperandrogenism, represented by elevated serum free testosterone, resulted in an aberrant circulating microRNA (miRNAs) expression profile and whether miRNAs can identify those PCOS women with metabolic syndrome (MetS). Accordingly, we measured serum levels of miRNAs as well as biochemical markers related to MetS in a case-control study of 42 PCOS patients and 20 Controls. Patients were diagnosed based on the Rotterdam consensus criteria and stratified based on serum free testosterone levels (?0.034 nmol/l) into either a normoandrogenic (<i>n</i> = 23) or hyperandrogenic (<i>n</i> = 19) PCOS group. Overall, hyperandrogenic PCOS women were more insulin resistant compared to normoandrogenic PCOS women and had a higher prevalence of MetS. A total of 750 different miRNAs were analyzed using TaqMan Low-Density Arrays. Altered levels of seven miRNAs (miR-485-3p, -1290, -21-3p, -139-3p, -361-5p, -572, and -143-3p) were observed in PCOS patients when compared with healthy Controls. Stratification of PCOS women revealed that 20 miRNAs were differentially expressed between the three groups. Elevated serum free testosterone levels, adjusted for age and BMI, were significantly associated with five miRNAs (miR-1290, -20a-5p, -139-3p, -433-3p, and -361-5p). Using binary logistic regression and receiver operating characteristic curves (ROC), a combination panel of three miRNAs (miR-361-5p, -1225-3p, and -34-3p) could correctly identify all of the MetS cases within the PCOS group. This study is the first to report comprehensive miRNA profiling in different subgroups of PCOS women with respect to MetS and suggests that circulating miRNAs might be useful as diagnostic biomarkers of MetS for a different subset of PCOS.