Metabolic profiles characterizing different phenotypes of polycystic ovary syndrome: plasma metabolomics analysis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder accompanied with an increased risk of developing type 2 diabetes mellitus and cardiovascular disease; despite being a common condition, the pathogenesis of PCOS remains unclear. Our aim was to investigate the potential metabolic profiles for different phenotypes of PCOS, as well as for the early prognosis of complications. METHODS: A total of 217 women with PCOS and 48 healthy women as normal controls were studied. Plasma samples of subjects were tested using two different analytical platforms of metabolomics: 1H nuclear magnetic resonance (NMR) and gas chromatography/time-of-flight mass spectrometry (GC/TOF-MS). RESULTS: Our results showed that carbohydrate, lipid and amino acid metabolisms were influenced in PCOS. The levels of lactate, long-chain fatty acids, triglyceride and very low-density lipoprotein were elevated, while glucose, phosphatidylcholine and high-density lipoprotein (HDL) concentrations were reduced in PCOS patients as compared with controls. Additionally, the levels of alanine, valine, serine, threonine, ornithine, phenylalanine, tyrosine and tryptophan were generally increased, whereas the levels of glycine and proline were significantly reduced in PCOS samples compared to controls. Furthermore, the ratio of branched-chain amino acid to aromatic amino acid concentrations (BCAA/AAA) in PCOS plasma was significantly reduced in PCOS patients and was insusceptible to obesity and insulin sensitivity. CONCLUSIONS: Our results suggested that the enhanced glycolysis and inhibited tricarboxylic acid cycle (TAC) in women with PCOS. Decrease of BCAA/AAA ratio was directly correlated with the development of PCOS. Ovulatory dysfunction of PCOS patients was associated with raised production of serine, threonine, phenylalanine, tyrosine and ornithine. Elevated levels of valine and leucine, and decreased concentrations of glycine in PCOS plasma could contribute to insulin sensitivity and could be considered as the potential biomarkers for long-term risk assessment of diabetes mellitus.

ER-α36, a novel variant of estrogen receptor α, is involved in EGFR-related carcinogenesis in endometrial cancer.

OBJECTIVE: To explore the role of estrogen receptor-α36 (ER-α36) in epidermal growth factor receptor (EGFR)-related carcinogenesis in endometrial cancer. STUDY DESIGN: The expression of ER-α36, EGFR, and phospho-extracellular signal-regulated kinase was analyzed using immunohistochemistry in endometrial cancer samples. The cellular localization of ER-α36 and EGFR was determined using immunofluorescence in the endometrial cancer Hec1A cells. The level of phospho-extracellular signal-regulated kinase of Hec1A cells was determined using Western blotting after treatment with epidermal growth factor. RESULTS: Positive rate of ER-α36 was increased in high-stage (P = .03) and high-grade (P = .224) endometrial cancer; expression of ER-α36 and EGFR exhibited a significant positive correlation (r = 0.334, P = .025) and they showed substantial colocalization on the plasma membrane of glandular cells; phospho-extracellular signal-regulated kinase positive rate in ER-α36 positive group and EGFR positive group was higher than that of ER-α36 negative group (P = .014) and EGFR negative group (P = .016); finally, ER-α36 mediated epidermal growth factor-stimulated extracellular signal-regulated kinase activation in Hec1A cells. CONCLUSION: ER-α36 mediates EGFR-related extracellular signal-regulated kinase activation in endometrial cancer.

Review of the genus Taiwanomyrme Tsuneki, 1993 (Hymenoptera, Mutillidae, Mutillinae), with description of two new species from China.

Five species of Taiwanomyrme Tsuneki, 1993 are reviewed; two of them, T. latisquamula Tu, Lelej et Chen, sp. nov. (China: Guizhou) and T. impressoides Tu, Lelej et Chen, sp. nov. (China: Zhejiang, Fujian, Hunan), are described and illustrated. Smicromyrme taiwanus Tsuneki, 1993 is proposed as a new synonym for Taiwanomyrme friekae (Zavattari, 1913). A key to males and females of Taiwanomyrme and additions to the key of females of Oriental genera of the tribes Petersenidiini and Trogaspidiini are given. New ranges are given for T. basirufus (Chen, 1957) and T. impressus (Chen, 1957), specifically within China.

Review of the genus Cystomutilla André, 1896 (Hymenoptera: Mutillidae: Sphaeropthalminae: Sphaeropthalmini), with description of the new genus Hemutilla gen. nov. and four new species from China.

The species of the genus Cystomutilla André, 1896 are reviewed. A new genus Hemutilla Lelej, Tu et Chen, gen. nov. (type species Hemutilla granulata Tu, Lelej et Chen, sp. nov.) and four new species: H. tuberculata Tu, Lelej et Chen, sp. nov. (China: Henan, Shaanxi), H. ferrugineipes Tu, Lelej et Chen, sp. nov. (China: Hunan), H. granulata Tu, Lelej et Chen, sp. nov. (China: Zhejiang), and H. cheni Tu et Lelej, sp. nov. (China: Fujian) are described and illustrated. New combinations are proposed for Hemutilla hoozana (Zavattari, 1913), comb. nov. and H. bifurcata (Chen, 1957), comb. nov. A key to males and females of two species of Cystomutilla André and six species of Hemutilla gen. nov. is given.

Lower expression of ER-α36 is associated with the development of endometrial hyperplasia in PCOS patients.

OBJECTIVE: To explore the expression change of ER-α36 in endometria of PCOS patients. METHODS: Proliferative endometria were collected and divided into three groups: CE group (n=30), proliferative endometria from control women; PCOSE group (n=30), proliferative endometria from PCOS patients; HPCOSE group (n=15), hyperplastic endometria from PCOS patients. The cellular localization of ER-α36 and ER-α66 was analyzed by immunohistochemistry, and expression of ER-α36 and ER-α66 was determined by immunohistochemistry and Real-Time Quantitative PCR. The correlation between serum hormone concentration and expression of ER-α36 and ER-α66 was analyzed. RESULTS: ER-α36 was localized on the cell surface, cytoplasm and nucleus of glandular epithelial cells of both CE and PCOSE groups, mainly on the cell surface, and ER-α66 was localized on the nucleus. The protein and mRNA expression of ER-α36 was decreased from CE, PCOSE to HPCOSE group, while expression of ER-α66 showed no obvious difference among groups. The expression ratio of ER-α36 to ER-α66 of CE, PCOSE and HPCOSE group showed a decreasing tendency. The expression of ER-α36 and its expressive ratio to ER-α66 was negatively correlated with serum concentration of LH, LH/FSH, testosterone and androstenedione. CONCLUSIONS: Lower expression of ER-α66 is associated with the development of endometrial hyperplasia in PCOS patients.

Characteristics of abnormal menstrual cycle and polycystic ovary syndrome in community and hospital populations.

BACKGROUND: Polycystic ovary syndrome (PCOS) is considered to be the most common endocrine disorder in women of reproductive age. The involvement of an abnormal menstrual cycle in the etiology of PCOS remains unclear. We aimed to analyze the characteristics of abnormal menstrual cycles and their association with PCOS in community and hospital patient populations. METHODS: Women with PCOS identified from 2111 permanent female residents in the community of Beijing and 506 outpatients obtained from the reproductive clinic of Peking University Third Hospital were recruited for this study, comprising the PCOS community group and the PCOS hospital group, respectively. Each group was further divided into four subgroups according to the length of menstrual cycles: <21 days; 21-34 days; 35-60 days; and >60 days. Women in each group were interviewed using a questionnaire to assess factors including age, age of menarche, menstrual cycle history, related family history, and modified Ferriman-Gallwey (mF-G) score. All women received transvaginal ultrasound scan and had fasting blood samples taken for endocrine evaluation. A two-tailed P value of <0.05 was considered significant. RESULTS: In the community population, the prevalence of abnormal menstrual cycle was 27.19% (574/2111). The prevalence of PCOS in the community was 6.11% (129/2111) according to Rotterdam criteria. In the community group, the most common menstrual cycle length was 35-60 days, whereas for the hospital group, it was >60 days. In both the community and hospital groups, the most common phenotype of PCOS was that of Oligo/amenorrhea+PCO+ hyperandrogenism (HA) (O+P+H) (P=0.000). With increasing cycle length of 35-60 days to >60 days, the percentages of Oligo/amenorrhea+PCO (O+P) and O+P+H were found to significantly decrease in the community group and significantly increase in the hospital group (P=0.000 for each). In the hospital group, as the menstrual cycle length increased from 35-60 days to >60 days, the rate of spontaneous abortion increased significantly (P=0.000), meanwhile the rate of poorly-secreted endometrium and abnormal endometrial hyperplasia increased significantly (P=0.000). CONCLUSIONS: The prevalence of PCOS in the Beijing community of women was 6.11%. Oligo/amenorrhea was the most common type of abnormal menstrual cycle and may be an indicator for PCOS and endometrial lesions. Gynecologists should seek relevant medical information from women in the community to promptly diagnose PCOS and then follow up patients for potential development of subsequent complications.