Bisphenol A analogues and metabolic syndrome in women with polycystic ovary syndrome.

Bisphenols (BPs) have become a chemical group of special interest due to their ability to interfere with the endocrine system and their ubiquitous presence in the environment. As some of them possess mild estrogenic and anti-androgenic effects, they might be associated with the diagnosis of polycystic ovary syndrome (PCOS). Acting on multiple tissues, BPs exposure may lead to metabolic derangements characteristic for metabolic syndrome (MetS). Therefore, the aim of this study was to determine the potential relationship between exposure to some BPA analogues and features of the MetS in women with PCOS. Serum BPE, BPC, BPG, BPM, BPP, BPZ, BPFL, and BPBP concentrations did not differ significantly between the PCOS (n = 135) and the control subjects (n = 104). However, women whose serum BPM and BPP concentrations were in the highest tertile were more likely to be diagnosed with PCOS (adjusted OR; [95%CI] 0.43; [0.20; 0.89], P < 0.001 and 0.56; [0.27; 0.96], P = 0.049, consequently). Serum concentrations of BPs were not associated with the MetS diagnosis in the PCOS group. There was a negative correlation between the concentrations of serum BPBP and total serum cholesterol (r = - 0.153; P = 0.019), BPE and serum testosterone (r = - 0.160; P = 0.014) as well as BPC and HDL-cholesterol (r = - 0.138; P = 0.036). There was a positive correlation between the concentrations of BPP and serum triglycerides (r = 0.138; P = 0.036). Our results point to the potential association between exposure to BPM, BPP, and the diagnosis of PCOS, along with the impact of BPBP, BPE, BPC, and BPP on the metabolic features of the MetS.

Alteration of Branched-Chain and Aromatic Amino Acid Profile as a Novel Approach in Studying Polycystic Ovary Syndrome Pathogenesis.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects reproductive-age women and predisposes them to the development of metabolic disturbances. Recent research has shown that several metabolic factors may play a role in PCOS pathogenesis, and it has been suggested that an alteration in the amino acid profile might be a predictive sign of metabolic disorders. Metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) are concepts that have attracted scientific attention; however, a universal definition has not been established yet for these terms. Already existing definitions of MHO involve the coexistence of obesity with the absence or minimal presence of other metabolic syndrome parameters. A group of 326 women, 209 diagnosed with PCOS and 117 healthy individuals, participated in this study. Multiple parameters were assessed, including anthropometrical, biochemical, and hormonal ones, and gas-liquid chromatography, combined with tandem mass spectrometry, was used to investigate the amino acid profile. Statistical analysis revealed noticeably higher levels of all aromatic amino acids in PCOS women compared to the control group: phenylalanine 47.37 ± 7.0 vs. 45.4 ± 6.09 nmol/mL (p = 0.01), tyrosine 61.69 ± 9.56 vs. 58.08 ± 8.89 nmol/mL (p < 0.01), and tryptophan 53.66 ± 11.42 vs. 49.81 ± 11.18 nmol/mL (p < 0.01); however, there was no significant difference in the "tryptophan ratio" between the PCOS and control group (p = 0.88). A comparison of MHO and MUO PCOS women revealed that LAP, leucine, and isoleucine concentrations were significantly higher among the MUO subgroup: respectively, 101.98 ± 34.74 vs. 55.80 ± 24.33 (p < 0.001); 153.26 ± 22.26 vs. 137.25 ± 25.76 nmol/mL (p = 0.04); and 92.92 ± 16.09 vs. 82.60 ± 18.70 nmol/mL (p = 0.02). No significant differences in BMI, fasting glucose, and HOMA-IR between MHO and MUO were found: respectively, 35.0 ± 4.8 vs. 36.1 ± 4.6 kg/m2 (p = 0.59); 88.0 ± 6.0 vs. 87.73 ± 6.28 mg/dL (p = 0.67); and 3.36 ± 1.70 vs. 4.17 ± 1.77 (p = 0.1). The identification of altered amino acid profiles in PCOS holds potential clinical implications. Amino acids may serve as biomarkers for diagnosing and monitoring the metabolic status of individuals with PCOS. The alteration of BCAAs and AAAs may be involved in PCOS pathogenesis, but the underlying mechanism should be further investigated.

Searching for the primary metabolic alterations of polycystic ovary syndrome by application of the untargeted metabolomics approach.

Despite a large number of studies, the pathogenesis of polycystic ovary syndrome (PCOS) still remains unexplained. In light of ambiguous observations reported in metabolomics, there is a need to carry out studies focusing on confirming the discriminating power of the proposed metabolomics biomarkers. Our research aimed to perform a validation study of metabolites detected in our previous study from serum samples, on the new set of samples obtained from PCOS women and healthy controls to confirm previously selected compounds. Additionally, the second biological matrix - urine - was used to get a more comprehensive insight into metabolic alterations. We applied two analytical techniques - gas chromatography and liquid chromatography coupled with mass spectrometry to analyze both serum and urine samples obtained from 35 PCOS patients and 35 healthy women. Thank to our approach, we identified and described a comprehensive set of metabolites altered in PCOS patients. Results of our study indicate increased steroid hormone synthesis, alteration in sphingo- and phospholipids metabolism, and disturbed fatty acids metabolism. Moreover, the citric acid cycle, γ-glutamyl cycle, vitamin B metabolism, and a few primary amino acids like tryptophan, phenylalanine, histidine, and alanine are altered.

Specific Alteration of Branched-Chain Amino Acid Profile in Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in reproductive age women; it is a complex health issue with numerous comorbidities. Attention has recently been drawn to amino acids as they are molecules essential to maintain homeostasis. The aim of the study was to investigate the branch chain amino acid (BCAA) profile in women with PCOS. A total of 326 women, 208 diagnosed with PCOS and 118 healthy controls, participated in the study; all the patients were between 18 and 40 years old. Anthropometrical, biochemical and hormonal parameters were assessed. Gas-liquid chromatography combined with tandem mass spectrometry was used to investigate BCAA levels. Statistical analysis showed significantly higher plasma levels of BCAAs (540.59 ± 97.23 nmol/mL vs. 501.09 ± 85.33 nmol/mL; p < 0.001) in women with PCOS. Significant correlations (p < 0.05) were found between BCAA and BMI, HOMA-IR, waist circumference and total testosterone levels. In the analysis of individuals with abdominal obesity, there were significant differences between PCOS and controls in BCAA (558.13 ± 100.51 vs. 514.22 ± 79.76 nmol/mL) and the concentrations of all the analyzed amino acids were higher in the PCOS patients. Hyperandrogenemia in PCOS patients was associated with significantly higher leucine, isoleucine and total BCAA levels. The increase of BCAA levels among PCOS patients in comparison to healthy controls might be an early sign of metabolic alteration and a predictive factor for other disturbances.

Serum bisphenol A analogues in women diagnosed with the polycystic ovary syndrome - is there an association?

Due to the endocrine disrupting effects of bisphenol A (BPA) several governmental authorities have banned its use and the manufacturers had to find alternative substances with similar chemical properties. This led to the increase in the use of so-called BPA analogues, which however also turn out to possess mild estrogenic and ani-androgenic properties and thus, may cause fertility problems and sex-hormone dependent endocrinopathies. The aim of this study was to evaluate the potential association between the exposure to BPA and its two analogues: BPS and BPF, with the diagnosis of the polycystic ovary syndrome (PCOS), which remains the most common female endocrinopathy. Serum concentrations of BPA, BPS and BPF were measured using high performance liquid chromatography method with tandem mass spectrometry (HPLC-MS/MS) among 199 women with PCOS and 158 control subjects. In women with PCOS serum BPS concentrations were significantly higher compared to the control subjects (geometric mean [95% CI]: 0.14 ng/mL [0.10; 1.17] vs. 0.08 ng/mL [0.06; 0.09], P = 0.023). Serum BPA and BPF concentrations did not differ between the studied groups. There was however a negative correlation between serum BPA and HOMA-IR (r = - 0.233, P = 0.001) and TST (r = - 0.203, P = 0.006) in women with PCOS. No correlations were found between the serum BPs and other metabolic parameters such as serum lipids, insulin, DHEA-S, androstenedione and FAI. When studying the association between serum BPA analogues and PCOS it turned out that women whose serum BPS concentrations were in the first tertile were more likely to be diagnosed with this endocrinopathy (OR [95% CI]: 1.21 [1.04; 3.46], P = 0.017). This association was also statistically significant when adjusted for age, education, BMI, smoking, income, and alcohol consumption (adjusted OR [95% CI]: 1.12 [1.03; 3.71], P = 0.029). These results point to the potential association between the exposure to BPS and the diagnosis of PCOS. The role of BPA is not clear and warrants further studies.

Advancement in Determination of Phthalate Metabolites by Gas Chromatography Eliminating Derivatization Step.

A gas chromatography-mass spectrometry (GC-MS) method to determine polar and thermally unstable phthalate metabolites [monomethyl phthalate-MMP, monoethyl phthalate-MEP, mono-n-butyl phthalate-MnBP, mono-(2-ethylhexyl) phthalate-MEHP] has been developed. This is the first report presenting the separation of monophthalates without derivatization step and any additional equipment or special injection port. Injection parameters (temperature, pressure, time, and volume of injection), chromatographic separation (retention gap, temperature program), and MS detection/identification (working parameters, ion selection) were investigated. Mechanisms and phenomena occurring under different conditions in the GC injector were evaluated and discussed. The limits of detection (LODs) of MMP, MEP, MnBP, MEHP in the protocol were 0.049, 0.036, 0.038, and 0.029 ng (per 2 µL of injection), respectively. The response of the monophthalates was found to be linear in the tested concentration range (for MMP: 0.15-100 ng, MEP and MnBP: 0.11-100 ng, MEHP: 0.087-100 ng per 2 µL) with the coefficient of determination higher than 0.9817 and inter-day precision in the range of 1.4-5.4%. The developed method is fast, easy and repeatable. Moreover, it allows for the elimination of derivatization agents, reduction of toxic waste production and simplification of analytical procedure.

Structural studies of copper(II) complexes with 2-(2-aminoethyl)pyridine derived Schiff bases and application as precursors of thin organic-inorganic layers.

Cu(ii) complexes with Schiff bases derived from 2-pyridin-2-ylethanamine were obtained and characterized by UV-Vis, fluorescence, and IR spectra. The X-ray crystal structures determined for [Cu(ii)(epy(di-t-Buba))Cl] × 0.042H2O and [Cu(ii)(epy(di-t-Buba))O2CCH3] revealed tetrahedral distortion of the Cu(ii) coordination sphere in the solid phase. For both molecules the Cu(ii) ions were found in tetragonal environments, as was confirmed by the values of EPR g-matrix diagonal components. The thermal properties of the complexes and the gas phase composition were studied by TG/IR techniques. Thin layers of the studied copper(ii) complexes were deposited on Si(111) by a spin coating method and characterized by scanning electron microscopy (SEM/EDS), atomic force microscopy (AFM) and fluorescence spectra. For copper(ii) layers the most intensive fluorescence band from intra-ligand transition was observed between 498 and 588 nm. The layers' fluorescence intensity was related to the rotation speed and deposition time.