Elevated expressions of SHP2 and GAB2 correlated with VEGF in eutopic and ectopic endometrium of women with ovarian endometriosis

Abstract

Aims: Protein tyrosine phosphatase Src-homology-2-domain-containing phosphatase 2 (SHP2) and adaptor protein Grb2-associated binding protein 2 (GAB2) can bind to each other in various signal transduction. However, the expression of SHP2 and GAB2 have not been investigated in endometriosis. The aim of the study was to evaluate the expressions of SHP2 and GAB2, and explore the correlation with Ki67 and VEGF in ovarian endometriosis.

Materials and methods: The protein expressions and localizations were assessed immunohistochemically in ectopic, eutopic endometrium and normal endometrium from patients with (n?=?30) and without (n?=?30) ovarian endometriosis.

Results: SHP2 was mainly present in the endometrial glandular epithelium, with increased expression in eutopic endometrium and even higher expression in ectopic endometrium compared to control endometrium (p?<?.05). GAB2 was immunolocalized in endometrial epithelium and stroma, increasing its expression from control endometrium to eutopic and ectopic endometrium (p?<?.05). Positive correlation was found between SHP2 and GAB2 in endometrium (p?<?.01). SHP2 and GAB2 both positively correlated with VEGF (p?<?.05), but not Ki67 in endometrium.

Conclusions: We provide the first evidence that the protein expressions of SHP2 and GAB2 were elevated in ectopic and eutopic endometrium, suggesting GAB2-SHP2 axis regulating VEGF might contribute to the pathomechanism of endometriosis.     

Fibrinogen alpha chain is up-regulated and affects the pathogenesis of endometriosis

Research questionIn the group's previous study, fibrinogen alpha chain (FGA) was identified as an up-regulated differential protein that was highly expressed in women with endometriosis. The current study investigated the expression and effects of FGA in endometriosis. It also evaluated the effects of FGA on human endometrial stromal cells and studied the possible mechanism.DesignThis was a cross-sectional analysis of FGA expression in plasma and endometrial tissue of matched eutopic and ectopic samples from women with endometriosis undergoing laparoscopic surgery and samples from women without endometriosis. Forty-four patients with endometriosis and 32 healthy control subjects who donated plasma for FGA analysis, including 26 matched cases of eutopic and ectopic endometria from endometriosis patients and 22 endometria from healthy control subjects, were analysed. The effects of FGA were studied in a human endometrial stromal cell line after transfection with FGA short interfering RNA (siRNA).ResultsFGA concentrations in serum and expression in eutopic and ectopic endometrial tissue were significantly higher in women with endometriosis than controls (P < 0.05 and P < 0.01 respectively), whereas FGA expression was not significantly different in eutopic compared with ectopic endometrial tissues from the same patients. High FGA concentrations in serum were related to disease stage and ovarian involvement, but were not affected by age and menstrual cycle. The knockdown of FGA expression by FGA siRNA inhibited hEM15A cellular adhesion, migration and invasion, and attenuated matrix metalloproteinase-2 (MMP-2) expression.ConclusionsHigh FGA expression in endometriosis was closely related to disease severity and affected cell adhesion, migration and invasion, which might play an important role in the pathogenesis of endometriosis.     

The expression of cytokines IFN-γ, IL-4, IL-17A,and TGF-β1 in peripheral blood and follicular fluid of patients testing positive for anti-thyroid autoantibodies and its influence on in vitro fertilization and embryo transfer pregnancy outcomes

Abstract

The aim of this work was to study the expression of the cytokines IFN-γ, IL-4, IL-17?A, and TGF-β1 in peripheral blood and follicular fluid (FF) of patients positive for antithyroid autoantibodies (ATA⁺) with normal thyroid gland function and the influence of these autoantibodies on in vitro fertilization and embryo transfer (IVF-ET) pregnancy outcomes. Nineteen patients were in the ATA⁺ group, and 27 patients tested negative for anti-thyroid autoantibody (ATA^?). Blood samples were drawn from the two groups of patients on the oocyte retrieval day and the 5th and 14th days of transplantation; in addition, FF was extracted on the oocyte retrieval day from both groups of patients and tested through enzyme-linked immunosorbent assay (ELISA) for IFN-γ, IL-4, IL-17?A, and TGF-β1. For the ATA⁺ group, the concentration of IFN-γ increased whereas the concentration of TGF-β1 decreased in peripheral blood on the oocyte retrieval day (p?<?.05); the concentration of IL-4 decreased in peripheral blood on the 5th and 14th days of transplantation for the ATA⁺ group (p?<?.05); further, the concentration of IL-17?A increased whereas that of TGF-β1 decreased in FF (p?<?.05). The ratio of IL-17?A/TGF-β1 in the ATA⁺ group significantly increased in FF and peripheral blood on the oocyte retrieval day and the 14th day of transplantation (p?<?.05). The ratio of IL-17?A/TGF-β1 in FF of the pregnant patients was significantly lower than in the non-pregnant patients (p?<?.05). The findings suggested that the ratio between pro-inflammatory and anti-inflammatory cytokines was adversely affected; therefore, adverse pregnancy outcomes of patients with ATA⁺ undergoing IVF-ET treatment may be attributed to immunological mechanisms.     

The effects of α-zearalanol and estradiol benzoate on expression of c-myc,c-fos and epidermal growth factor receptor mRNAs in breast tissues implanted into nude mice

This study was designed to evaluate the effects of a novel phytoestrogen, α-zearalanol (α-ZAL), and estradiol benzoate (B-E₂), on c-myc, c-fos, and EGFR expression in normal human breast tissues implanted into nude mice. A xenograft-model, pieces of normal human breast tissue implanted subcutaneously into 9–10-week-old athymic nude mice, was established. The mice were divided into five groups subjected to the following treatments: normal saline (Controls); α-ZAL at 1 and 5?mg/kg; and estradiol benzoate (B-E₂) at 1 and 5?mg/kg. Treatment was given every other day, and human breast tissues were removed for experiments after treatment for 30 days. The expression of c-myc, c-fos, and EGFR mRNAs were determined by in situ hybridization. α-ZAL decreased expression of c-myc (p?<?0.05). About 1?mg/kg α-ZAL increased EGFR expression (p?<?0.05) and two dosage of α-ZAL increased c-fos expression (p?<?0.01) compared with control. B-E₂ significantly increased expression of c-myc, c-fos, and EGFR mRNAs expression compared with controls (p?<?0.01). The extents of the increases in EGFRmRNA expression induced by α-ZAL and in c-fos mRNA by 5?mg/kg α-ZAL were lower than those induced by B-E₂ (p?<?0.01). These data suggest that the phytoestrogen α-ZAL may be safer than estrogen on breast.     

Follicle-stimulating hormone associates with metabolic factors in postmenopausal women

Abstract

Current studies have focused more on the relationships among estrogen, androgen, and metabolic syndrome (MetS). The main aim of the study was to investigate whether the variation of FSH is associated with metabolic factors in postmenopausal women. A total of 561 postmenopausal women aged 39–69 years were selected. FSH, estradiol, fasting blood glucose, and lipid profiles were analyzed. Compared with women in the highest FSH quartile, women in the lowest quartile had higher body mass index (BMI), fast blood glucose (FBG), triglyceride (TG), blood pressure, and serum estradiol (E₂) but lower high-density lipoprotein (HDL) (all p?<?.05). Compared with women in the groups of normal levels of MetS biomarkers, women in the abnormal groups had lower FSH (all p?<?.01). Increased quartiles of FSH were associated with significantly decreased rates of abnormal levels of metabolic factors (all p?<?.05). High FSH levels had protective effects regarding SBP, DBP, and FBG, with odds ratios (ORs) of 0.84 (95% CI 0.76–0.92, p?<?.001), 0.85 (95% CI 0.78–0.94, p?<?.01), 0.90 (95% CI 0.83–0.98, p?<?.01), respectively. Low FSH appears to be a risk factor of all domains of MetS in postmenopausal women, which merits further study.     

The different dosages of estrogen affect endometrial fibrosis and receptivity,but not SDF-1/CXCR4 axis in the treatment of intrauterine adhesions

Objective: The study was to evaluate whether fibrotic markers, endometrial receptivity markers and SDF-1/CXCR4 had been changed in the treatment of intrauterine adhesions (IUAs) by different dosages of estrogen.

Study design: A total of 39 patients with IUAs were treated with EV 4?mg or 9?mg randomly post-surgery. TGF-β1/MMP-9, VEGF/αvβ3 and SDF-1/CXCR4 were detected in endometrial tissue before and after treatment by real-time PCR and Western blot.

Results: TGF-β1 and MMP-9 expression significantly decreased after treatment for 3?months than before (p?p?p?p?p?>?.05). SDF-1 presented an upward tendency at early phase, and it came back to the level of pre-surgery. But there were no significant difference between treatment with 4?mg and 9?mg in the rate of menstrual restoration and pregnancy follow-up 3?months after the treatment.

Conclusions: Endometrium fibrosis may be inhibited and endometrium receptivity may be improved by estrogen with moderate dosage therapy. Compared to the large one, it seems to be advantageous.     

Inducible nitric oxide inhibitor aminoguanidine,ameliorated oxidative stress,interleukin-6 concentration and improved brain-derived neurotrophic factor in the brain tissues of neonates born from titanium dioxide nanoparticles exposed rats

Abstract

Introduction: An interaction between oxidative stress, neuroinflammation, and nitric oxide (NO) has been suggested to have a role neurotoxicity. The aim of current research was to investigate the effect of aminoguanidine (AG) as an inducible NO synthase (iNOS) inhibitor, on brain-derived neurotrophic factor (BDNF), oxidative stress, and interleukin-6 (IL-6) concentrations in the brain tissues of neonates born from the rats exposed to titanium dioxide nanoparticles (TiO2 NPs) during gestation.

Methods: The pregnant rats were grouped into three and received: (1) saline, (2) TiO2 (200?mg/kg, gavage), and (3) TiO2-AG [200?mg/kg intraperitoneal (IP)]. The treatment was started since the second gestation day up to the delivery time. The neonates born from the rats were deeply anesthetized, sacrificed, and the brains were collected for biochemical evaluations.

Results: The neonates born from the rats exposed to TiO₂ showed a lower BDNF (p?<?.001) but a higher IL-6 (p?<?.01) concentrations in their hippocampal tissue. TiO₂ exposure also increased malondialdehyde (MDA) (p?<?.001) and NO metabolites (p?<?.001), while diminished thiol (p?<?.001), superoxide (SOD) (p?<?.001), and catalase (CAT) (p?<?.001) in all hippocampal, cortical, and cerebellar tissues. Administration of AG improved BDNF (p?<?.01) but attenuated IL-6 (p?<?.01) concentrations in the hippocampal tissue. AG also decreased MDA (p?<?.001) and NO metabolites (p?<?.01–p?<?.001), while increased thiol (p?<?.01–p?<?.001), SOD (p?<?.001), and CAT (p?<?.05–p?<?.001) in all cerebellar, hippocampal, cortical, and tissues.

Conclusion: The results of the current research revealed that iNOS inhibitor AG, ameliorated oxidative stress, IL-6 concentration, and improved BDNF in the brain tissues of neonates born from TiO₂ NPs exposed rats.     

The effects of hypoxia on growth cones in the ovine fetal brain

Objective: This study was designed to investigate the effects of hypoxia on neural process proliferation by studying its effects on growth cone tubulin and insulin-like growth factor (IGF)-I receptor content.

Methods: Six fetal lambs were catheterized in the brachial artery and vein. Maternal oxygenation was reduced in steps from a fractional inspired oxygen concentration (FiO₂) of 20% to 6% by addition of nitrogen to the inhaled gas mixture for a period of 4?h of reduced oxygen intake. Fetal arterial blood was sampled after the maternal FiO₂ and oxygen were stable for >?5?min at maternal FiO₂ of 20% to 6%. Controls were obtained from normoxic fetuses whose ewes had similar surgery and were kept at an FiO₂ of 20% throughout the experiment. Growth cones were isolated from the fetal cerebrum and cerebellum. α-Tubulin and IGF-I receptors were quantified by immunoblotting. Tubulin and IGF-I receptor mRNA expressions were quantified by real-time polymerase chain reaction.

Results: Maternal nitrogen breathing reduced fetal arterial pH from 7.32?±?0.06 to 6.99?±?0.02 (p?<?0.001). Hypoxia increased IGF-I receptors from 143?±?10 to 327?±?14 (p?<?0.001) and from 272?±?26 to 396?±?34 (p?<?0.001) fluorescence units/μg protein in the cerebrum and cerebellum, respectively. It also increased α-tubulin from 713?±?30 to 1873?±?126 (p?<?0.001) and from 780?±?34 to 2362?±?79 (p?<?0.001) fluorescence units/μg protein in the cerebrum and cerebellum, respectively. Expression of IGF-I receptor mRNA increased significantly in the hypoxic animals both in the cerebrum and the cerebellum, but there was no change in expression of α-tubulin mRNA.

Conclusions: This increase in IGF-I receptor expression and growth cone content may be an adaptive response to hypoxia to maintain neurite growth by facilitating binding of IGF-I. Hypoxia also increased the growth cone level of α-tubulin but did not increase its mRNA expression, which may indicate an inability to polymerize tubulin and build microtubules.     

Outcomes of random start versus clomiphene citrate and gonadotropin cycles in occult premature ovarian insufficiency patients,refusing oocyte donation: a retrospective cohort study

Abstract

The aim of this study is to present the clinical outcomes of a random start, a spontaneous folliculogenesis protocol versus Clomiphene Citrate and Gonadotropin treatment in women with occult premature ovarian insufficiency. Women underwent treatment between 1 February 2009, and 30 May 2016. 41 women were treated with the random start protocol while 48 cases received ovarian stimulation with clomiphene and gonadotropins. All included cases met the criteria of 4?months of oligo-ovulation, follicular-stimulating hormone levels over 30?IU/L and anti-Mullerian hormone levels below 0.30?ng/mL. The random start protocol involved following the subjects for up to 6?months until spontaneous folliculogenesis occurred. The mean number of oocytes collected, mature oocytes, fertilized oocytes, and grade II embryos were significantly higher in the random start protocol (p?<?.05). The doses of gonadotropin administration and hCG were significantly lower in the random start protocol (p?<?.05). The clinical pregnancy and live birth rates were significantly higher in the random start protocol (p?<?.05). Likely stimulation is of little benefit in women with occult premature ovarian insufficiency. Observation while waiting for spontaneous folliculogenesis results in better outcomes, and less oocyte collections.     

G protein-coupled estrogen receptor 1 (GPER 1) mediates estrogen-induced,proliferation of leiomyoma cells

Abstract

G protein-coupled estrogen receptor 1 (GPER-1, formerly known as GPR30) has been proposed as the receptor for estrogen-induced, growth of leiomyomas though its precise mechanisms of action are not clear. We obtained leiomyoma cells (LC) and normal smooth muscle cells from 28 women (n?=?28, median age 38 years, median parity 1.0). We incubated them with 17-β estradiol (E₂), after blocking, or upregulating, expression of GPER-1 with ICI182,780 (a GPER-1 agonist) and siGPR30, respectively. We evaluated the role of GPER-1 in the mitogen-activated protein kinase (MAPK) signaling pathway using Western blot analysis. We studied cell proliferation with 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide, and, mitotic activity with phosphohistone H3 (PPH3) expression in leiomyoma, and, matched, normal, smooth muscle tissues using standard immunohistochemistry. Downregulation of GPER-1 expression with siGPR30 partially attenuated the E₂-activated MAPK signaling pathway (p?<?0.01). Upregulation of GPER-1 with ICI182,780 enhanced the E₂-activated MAPK signaling pathway (p?<?0.01). ICI182,780 enhanced E₂-induced proliferation of LC (p?<?0.01), while knock down of the GPER-1 gene with GPER-1 small interfering RNA partially inhibited E₂-induced cell proliferation (p?<?0.01). There were no significant differences in PPH3 expression between LCs and normal smooth muscle tissues (p?>?0.05). Neither ICI182,780 nor siGPR30 increased mitosis in LCs (p?>?0.05). Our results indicate that GPER-1 mediates proliferation of estrogen-induced, LC by activating the MAPK pathway, and, not by promoting mitosis.     

Serum activities of dipeptidyl peptidase-4 and adenosine deaminase in polycystic ovary syndrome: association with obesity

Dipeptidyl peptidase-4 (DPP-4) plays a role in metabolic and inflammatory diseases. Increased adenosine deaminase (ADA) has been suggested to induce insulin resistance and inflammation. We measured serum DPP-4 and ADA activities. Serum ADA activity was significantly higher in PCOS group (p?=?.006), whereas there was no difference in serum DPP-4 activity between the groups (p?>?.05). When the study subjects were divided into four groups in terms of obesity; an increasing trend in serum ADA activity between the groups was observed and ADA activity was significantly higher in overweight and obese patients with PCOS than nonobese controls (p?=?.016), there were no significant differences between the other groups (p?>?.05). A positive correlation was found between ADA and BMI in the whole group (p?=?.022). Multivariate regression analyses revealed that significant determinants were diastolic blood pressure, ADA, and the presence of PCOS for DPP-4 (R²?=?0.344, F?=?9.079, p?<?.001); the presence of PCOS and DPP-4 for ADA (R²?=?0.123, F?=?6.302, p?=?.003). We demonstrated increased serum ADA activity as well as its association with obesity in PCOS, while there was no change in serum DPP-4 activity in women with PCOS.     

Alterations in Th1/Th2 cytokine concentrations in early neonatal life

Objective:?To determine postnatal changes in neonatal serum concentrations of interferon-γ (IFN-γ), interleukin-4 (IL-4) and its soluble receptor (sIL-4R). Methods:?Forty-five healthyterm neonates, 25 of the neonates' mothers and 27 healthyadults (controls) participated in the study. Cytokine concentrations were measured in blood samples from the umbilical cord, from the neonates on the 1st and 5th dayafter birth, from mothers and from controls. Results:?IFN-γ concentrations were significantlylower in the umbilical cord, compared to concentrations in the controls (p?<?0.04), and increased significantlyfrom the umbilical cord to levels in neonates on day5 (p?<?0.03). In mothers and the umbilical cord, IFN-γ concentrations were dependent on the mode of delivery, being higher after vaginal delivery than after elective Cesarean section (p?<?0.005; p?<?0.006, respectively). IL-4 concentrations in the umbilical cord for 1-day and 5-day neonates were significantlyelevated compared to those in mothers (p?<?0.001; p?<?0.0007; p?<?0.0001, respectively) and controls (p?<?0.05; p?<?0.01; p?<?0.006, respectively). sIL-4R concentrations in all neonatal samples were significantlyelevated compared to those in controls (p?<?0.0001), the highest being found in 1-day-old neonates. A strong negative correlation was found between IL-4 and sIL-4R concentrations in 1- and 5-day-old neonates (r?=??0.48, p?<?0.002; r?=??0.45, p?<?0.0065, respectively). Moreover, IFN-γ/IL-4 ratio increased significantly from the umbilical cord to 5 days of life (p?<?0.03). Conclusion:?Our findings indicate an earlier development of IL-4 than IFN-γ, which could be viewed as a developmental characteristic in the ontogeny of the immune system.     

Estrogen biosynthesis in breast adipose tissue during menstrual cycle in women with and without breast cancer

Abstract

Circulating estrogens fluctuate during the menstrual cycle but it is not known whether this fluctuation is related to local hormone levels in adipose tissue. We analyzed estrogen concentrations and gene expression of estrogen-regulating enzymes in breast subcutaneous adipose tissue in premenopausal women with (n?=?11) and without (n?=?17) estrogen receptor-positive breast cancer. Estrone (E₁) was the predominant estrogen in premenopausal breast adipose tissue, and E₁ and mRNA expression of CYP19A1 in adipose tissue correlated positively with BMI. Adipose tissue estradiol (E₂) concentrations fluctuated during the menstrual cycle, similarly to the serum concentrations. In women with breast cancer median adipose tissue E₁ (1519 vs. 3244, p?<?.05) and E₂ (404 vs. 889?pmol/kg, p?<?.05) levels were lower in the follicular than in the luteal phase whereas in control women no significant differences were observed. In the follicular phase, mRNA expressions of HSD17B1 (median 0.06; interquartile range 0.05–0.07 vs. 0.17; 0.03–0.2, p?=?.010) and CYP19A1 (0.08; 0.07–0.14 vs. 0.22; 0.09–0.54, p?=?.025) were lower in women with breast cancer than in controls. In conclusion, the changes in adipose tissue E₁ and E₂ concentrations and the estrogen-regulating CYP19A1 and HSD17B1 during the menstrual cycle may be related to dysfunctional local estrogen metabolism in women with breast cancer.     

The inhibition of reactive oxygen species (ROS) by antioxidants inhibits the release of an autophagy marker in ectopic endometrial cells

ObjectiveThe aim of this study was to evaluate the role of oxidative stress and reactive oxygen species (ROS) in the pathogenesis of endometriosis (EMs) and to investigate the role of antioxidant therapy on autophagy and the outcome of EMs.Materials and methodsExperimental rats were given an peritoneal perfusion of N-acetyl-l-cysteine (NAC, 200 mg/kg) or catalase (CAT, 2000 U/mL). Immunofluorescence was then used to detect microtubule-associated protein light chain 3 (LC3). Western blotting was used to determine the levels of Beclin-1 protein while enzyme-linked immunosorbent assays (ELISAs) were used to measure ROS levels after treatment.ResultsFluorescent in situ hybridization showed that NAC and CAT influenced the levels of LC3, an autophagy marker; there were significantly lower levels of LC3 fluorescence in the EMs group (surgical group) of rats compared with controls (p < 0.05). Western blot analysis revealed a downregulation of Beclin-1 protein in both the NAC and CAT groups (p < 0.05) while ELISA revealed significantly lower levels of ROS in the NAC and CAT groups (p < 0.05).ConclusionThe antioxidants NAC and CAT significantly reduced levels of the autophagy marker LC3 and caused levels of Beclin-1 to significantly decrease. Consequently, antioxidant therapy shows potential for the future treatment of EMs.     

Effects of CDKN2B-AS1 on cellular proliferation,invasion and AKT3 expression are attenuated by miR-424-5p in a model of ovarian endometriosis

Research questionEndometriosis is a common and complicated gynaecologic disease. Long non-coding RNA CDKN2B-AS1 plays a crucial role in the development and progression of several cancers. Whether CDKN2B-AS1 contributes to endometriosis, however, remains unknown.DesignCellular proliferation, invasion and DNA synthesis abilities were assessed by CCK8, transwell and 5-ethynyle-2’-deoxyuridine assays. The expression of epithelial–mesenchymal transition markers and three isoforms of AKT was detected using Western blot. Real-time polymerase chain reaction was used to determine the relative expression levels of CDKN2B-AS1 and candidate miRNAs in ectopic, eutopic endometria and normal endometrial tissues. The relationship between CDKN2B-AS1 and miRNA was determined by luciferase reporter assays.ResultsThe relative expression level of CDKN2B-AS1 was up-regulated in eutopic and ectopic endometria. In endometrial stromal cells and Ishikawa cells, CDKN2B-AS1 overexpression promoted cellular proliferation and invasion, and increased the protein expression of vimentin but decreased the expression of E-cadherin. miR-424-5p was confirmed the target of CDKN2B-AS1 through bioinformatics tools and luciferase reporter assays. In addition, the enhanced effect of cellular phenotype of CDKN2B-AS1 overexpression was significantly attenuated by miR-424-5p overexpression. Furthermore, miR-424-5p was able to directly target AKT3 through luciferase reporter assay. Mechanistically, CDKN2B-AS1 acts as a ceRNA by sponging miR-424-5p and targets AKT3.ConclusionsThe cellular mechanism of CDKN2B-AS1 in endometriosis was confirmed; CDKN2B-AS1 may be a potential target for ovarian endometriosis therapy.     

It’s not as bad as you think: menopausal representations are more positive in postmenopausal women

Introduction: The menopausal transition is associated with underlying hormonal changes that can contribute to a range of physical and emotional symptoms. Psycho-social factors including attitudes and internal representations play a central role in women’s experience of the menopause, but very little is known about how representations might differ across menopausal stages.

Methods: A sample of 387 women aged 40–60 completed a postal questionnaire that included the menopausal representations questionnaire, the emotional representation subscale adapted from the illness perception questionnaire, and data on menopausal status.

Results: Significant differences across menopausal stages were found for both cognitive [F(2, 381)?=?4.32, p?<?.05, η²?=?0.022], and emotional [F(2, 381)?=?9.70, p?<?.01, η²?=?0.048] menopausal representations. Postmenopausal women had a significantly more positive cognitive representations of the menopause relative to perimenopausal women (standardised mean difference?=?0.25, p?>?.05). Postmenopausal women held a significantly more positive emotional representation of the menopause than both premenopausal (standardised mean difference?=?0.56, p?<?.05) and perimenopausal (standardised mean difference?=?0.43, p?<?.05) women.

Discussion: Women’s emotional and cognitive representations of the menopause are more positive among postmenopausal women, compared to women in the late premenopausal stage. This is consistent with the affective forecasting theory, which proposes the tendency to overestimate the intensity and duration of emotional reactions to future events. Given the association between representations and bothersomeness of menopausal symptoms, clinicians should educate women about their expectations, and challenge their negative beliefs about the menopause.     

Paraoxonase 1 (PON1) Q192R and L55M polymorphisms,lipid profile,lipid peroxidation and lipoprotein-a levels in Turkish patients with pregnancy-related disorders

Abstract

The aim of this study was to investigate the role of PON1Q192R and L55M single nucleotide polymorphisms(SNPs) and its association with the maternal levels of lipid parameters in gestational diabetes mellitus(GDM) and preeclampsia(PE). Ninety-nine pregnant with GDM, 97 pregnant with PE and 98 healthy pregnant were included in the study. No statistically significant difference was observed in the alleles or in the genotypes frequencies of SNPs between groups. In GDM patients, total cholesterol was higher in MM genotype of L55M gene (p?<?.05); Lp(a) were lower in LM genotype of the gene compared to their respective control (p?<?.05). In PE, HDL-C levels were higher in LM genotype (p?<?.05); LDL-C levels were lower in MM genotype of the gene compared to their respective control (p?<?.05). In PE patients, malondialdehyde(MDA) were higher in QQ genotype compared to their respective control (p?<?.05). Triglyceride levels were higher in PE patients with QR genotype compared with GDM patients with QR genotype (p?<?.05). Our results indicated that lipid profiles, Lp(a) and MDA levels showed significant differences in GDM and PE pregnants. These findings support the importance of the lipid profile, oxidized lipid and Lp(a) in different genotypes of L55M and Q192R in Turkish pregnant women with PE/GDM suggesting their roles in etiopathogenesis in these pregnancy-related disorders.     

Trends in primeval β-hCG level increment after fresh and frozen-thawed IVF embryo transfer cycles

Mid-trimester beta-human chorionic gonadotropin (BHCG) levels are considerably higher in pregnancies resulting from frozen embryo transfer (FET) compared with fresh (FRET), leading to a higher false positive rate in aneuploidy screening tests. We aimed to investigate the dynamics of BHCG increment and its predictive value for cycle outcome. A retrospective analysis of FRET and FET cycles. BHCG values on days 14 and 16 post embryo transfer were compared and stratified according to the number of sacs demonstrated on US scan at six weeks gestation, and pregnancy outcome (biochemical pregnancy, ectopic pregnancy, spontaneous abortion, and a singleton or twin birth). A prediction model for live birth was built. A total of 430 treatment cycles were analyzed. The average BHCG levels were significantly higher in FET compared with FRET group in nonviable pregnancies on day 14, 450 vs. 183?IU/L, p?<?.05 and day 16, 348 vs. 735?IU/L, p?<?.05, respectively. The increment of BHCG was significantly steeper in the FET compared with FRET group in biochemical pregnancies (F?=?6.485, p?=?.012*). Optimal cutoff level for live birth prediction in the FRET group was 211?IU/L (sensitivity 84%, specificity 76.2%) for day 14 and 440?IU/L (sensitivity 86.0% and specificity 72.5%) for day 16. The increment in BHCG differed significantly between the FRET and FET cycles in nonviable pregnancies. Nevertheless, the difference in BHCG levels observed in the second trimester in pregnancies conceived after FRET and FET cycle may begin as early as the fourth week of pregnancy.     

Leptin promotes ossification through multiple ways of bone metabolism in osteoblast: a pilot study

Abstract

Leptin may be a potential option in preventing osteoporosis for menopausal women. The objective of this study is to explore the molecular mechanism of leptin on bone metabolism in osteoblast. Primary osteoblasts were isolated from parietal bone of adult female rats. mRNA level of OB-Rb in osteoblasts was inhibited by siRNA to block leptin signal transmission. The whole genome expression was tested by using gene chip to preliminarily explore the molecular mechanism of leptin in regulating osteoblast activity. The optimal concentration of siRNA was 25?nM, resulting in a maximal inhibition of OB-Rb mRNA. Ossification (p?<?0.05) and bone mineralization (p?=?0.0001) were downregulated by inhibiting leptin signal transmission, while bone resorption (p?=?0.007), osteoblast differentiation (p?=?0.026) and negative regulation of bone remodeling (p?=?0.004) were upregulated. The expressions of some genes were regulated by OB-Rb siRNA. The expressions of alkaline phosphatase (p?=?0.014) and osteocalcin (p?=?0.002) were reduced, while that of vascular endothelial growth factor A (p?=?0.0076) and IL-6 (p?=?0.021) were increased. In a model of osteoblast, leptin positively promotes ossification through multiple ways including bone mineralization, remodeling, resorption and osteoblast differentiation, but which way plays the most critical role is not discussed in this study and needs to be clarified in future.     

Detecting and investigating the significance of high-frequency LOH chromosome regions for endometriosis-related candidate genes

To detect the high-frequency loss of heterozygosity (LOH) chromosome regions for ectopic endometrium of ovarian endometriosis (EMs) and to investigate the significance of high-frequency LOH chromosome regions in EMs, we obtained ectopic endometrium by laser capture microdissection (LCM (22 samples)), manual capture microdissection (MCM (18 samples)), and routine dissection (14 samples), respectively. After restriction and circularization-aided rolling circle amplification (RCA-RCA), LOH was detected at 12 microsatellite (MS) loci. The frequency of LOH was 59.09% (13/22) in LCM group, 61.11% (11/18) in the MCM group and 21.43% (3/14) in the routine dissection group. The latter was significantly lower when compared with the former two (p < 0.05). In the LCM group, candidate chromosome regions 17q21.31 and 9p21.3 had LOH frequencies of 23.8 and 13.6%, respectively. The highest LOH frequency was detected at the locus AAAT2 on chromosome 17q21.31 (40%). The chromosome region with the highest frequency of LOH for ectopic endometrium was 17q21.31, especially at the AAAT2 locus, which prompted that down regulation of the candidate genes nearby the locus might be one of the mechanisms of EMs pathogenesis. LCM combined with RCA-RCA is a reliable technique for analyzing endometrial LOH at multiple MS loci. MCM combined with RCA-RCA, which provided similar results, was more cost-effective.