辅助生殖患者宫腔粘连术后应用人工周期促内膜修复的疗效及对生育结局的影响

目的评价17-β雌二醇用于辅助生殖患者宫腔粘连术后促子宫内膜修复的效果及对生育结局的影响。方法 429例拟行体外受精-胚胎移植(IVF-ET)患者,因宫腔粘连经宫腔镜下行宫腔粘连分离术和放置宫内节育器术,215例术后应用17-β雌二醇+地屈孕酮行周期治疗(雌二醇2mg bid)2周期(实验组),214例不行周期治疗(对照组)。所有病例定期随诊,治疗结束后再行宫腔镜检查探查宫腔情况并取出宫内节育器,再行胚胎移植,随访治疗疗效及妊娠结局。结果实验组的宫腔镜治疗治愈率明显较对照组高,X2=-3.16,p=0.002,实验组术后胚胎移植临床妊娠率也明显较对照组高X2=-2.75,p=0.006。结论宫腔粘连术后采用17-β雌二醇周期治疗,不但有利于宫腔形态的恢复及内膜的修复,而且可以提高内膜的容受性,明显改善妊娠结局。     

Comparison between oral and vaginal estrogen usage in inadequate endometrial patients for frozen-thawed blastocysts transfer

Endometrial preparation with exogenous estrogen is a common practice in frozen-thawed embryo transfer (FET) cycles. The objective of this study was to compare the clinical outcomes of two endometrial preparation groups, oral estradiol valerate tablets (OEV) group versus vaginal estradiol (VE) tablets group, in inadequate endometrium patients. This retrospective, single-center, cohort study of patients undergoing FET treatment between Jan. 2012 and Jun. 2013, at an academic IVF center, included 247 patients (cycles) with endometrial thickness < 8 mm on day 13 of the hormone replacement cycle: OEV group included 69 patients (cycles) who received continuous OEV from day 1 onwards up to the day of progesterone supplement, while VE group included 178 patients (cycles) who taken OEV from day 1 to day 12, and used VE tablets from day 13 till the day of progesterone supplement. Patients in VE group required more days and higher dosage of estradiol, but had thinner endometrium on the day of transfer. However, the increase of endometrial thickness was more, when compared to OEV-treated patients. The implantation rate and pregnancy rate were, though not significantly, higher in VE group. Conclusions: Longer time of administration and higher dosage of estradiol usage did not have adverse effects on the clinical pregnancy rate. VE tablets may promote endometrial development and pregnancy success in FET cycles could not verify. Further study is needed to confirm the vaginal estradiol action on frozen-thawed embryo transfer cycles.     

8-Br-cAMP和血小板衍生生长因子对多囊卵巢综合征患者颗粒细胞E2生成的影响

目的:探讨8-溴-环磷酸腺苷(8-Br-cAMP)和血小板衍生生长因子(PDGF)对多囊卵巢综合征(PCOS)患者离体卵巢黄素化颗粒细胞雌二醇(E2)生成的影响.方法:收集体外授精-胚胎移植(IVF-ET)时PCOS患者(n=6)和正常对照(n=8)的黄素化颗粒细胞进行体外原代培养,在其培养的不同时间(0 h、48 h、120 h)以睾酮(10-7mol/L)作为底物,分别添加8-Br-cAMP(2 mmol/L)和(或)PDGF(10μg/L)于无血清培养液(TCM199)中,共培养3h后收集培养上清、细胞.用放射免疫法测定颗粒细胞分泌E2量;用考马斯亮蓝G250/BSA测颗粒细胞蛋白含量,以校正E2含量.结果:与对照组比较,8-Br-cAMP和PDGF在0 h、48 h和120 h均显著刺激PCOS组颗粒细胞分泌E2(P＜0.05);8-Br-cAMP和PDGF联合作用在48 h、120 h显著刺激PCOS组颗粒细胞分泌E2(P＜0.05).结论:8-Br-cAMP和PDGF均可加速PCOS患者卵巢颗粒细胞内雄激素向雌激素的转化;8-Br-cAMP和PDGF对颗粒细胞芳香化酶活性的调节作用是一致的.     

产后抑郁症患者雌、孕激素及催乳素变化的研究

目的:研究产后3d与42d雌二醇(E2)、孕酮(P)、催乳素(PRL)水平变化与产后抑郁症的关系。方法:采用Ed in-burgh(EPDS)抑郁量表评定152例产妇产后抑郁情况,比较产后3d及42d的抑郁症发病率,并对比其产后3d与42d的E2、P、PRL水平的差异。结果:抑郁症产后42d发病率明显低于产后3d(P<0.01);抑郁组产后3d、42d血清E2均低于正常组(P<0.05或P<0.01),产后42d血清P水平高于正常组(P<0.05);抑郁组产后3d、42d血清E2水平与EPDS量表分呈负相关性,产后42d血清P水平与EPDS量表分呈正相关性;PRL变化不恒定(P>0.05)。结论:产后体内雌孕激素变化可能是产后抑郁症的诱因之一。     

性激素对3T3-L1前脂肪细胞和脂肪细胞胰岛素敏感性的影响

目的观察不同浓度雌、雄激素对3T3-L1前脂肪细胞葡萄糖转运的影响,探讨性激素在胰岛素抵抗形成中的意义。方法体外培养3T3-L1前脂肪细胞,并诱导其分化成熟,利用2-脱氧-[3H]-D-葡萄糖掺入法,研究不同浓度的17β雌二醇、睾酮对胰岛素刺激的前脂肪细胞和脂肪细胞葡萄糖摄取能力的影响。结果10-8mol/L的17β雌二醇即能够抑制3T3-L1前脂肪细胞胰岛素刺激状态下的葡萄糖转运,且呈现明显的浓度依赖性抑制;而睾酮为10-8mol/L时3T3-L1前脂肪细胞胰岛素刺激状态下的葡萄糖转运并无明显影响,在浓度达到10-7mol/L开始出现抑制效应,浓度越高抑制效应越明显。结论性激素可以调节3T3-L1前脂肪细胞的胰岛素敏感性。     

Distribution of aromatase in the brain of the African cichlid fish Astatotilapia burtoni: Aromatase expression,but not estrogen receptors,varies with female reproductive-state

Estrogen synthesis and signaling in the brains of vertebrates has pleotropic effects ranging from neurogenesis to modulation of behaviors. The majority of studies on brain-derived estrogens focus on males, but estrogenic signaling in females likely plays important roles in regulation of reproductive cycling and social behaviors. We used females of the mouth brooding African cichlid fish, Astatotilapia burtoni, to test for reproductive state-dependent changes in estrogenic signaling capacity within microdissected brain nuclei that are important for social behaviors. Expression levels of the rate-limiting enzyme aromatase, but not estrogen receptors, measured by qPCR changes across the reproductive cycle. Gravid females that are close to spawning had higher aromatase levels in all brain regions compared to females with lower reproductive potential. This brain aromatase expression was positively correlated with circulating estradiol levels and ovarian readiness. Using chromogenic in situ hybridization we localized aromatase-expressing cells to ependymal regions bordering the ventricles from the forebrain to the hindbrain, and observed more abundant staining in gravid compared to mouth brooding females in most regions. Staining was most prominent in subpallial telencephalic regions, and diencephalic regions of the preoptic area, thalamus, and hypothalamus, but was also observed in sensory and sensorimotor areas of the midbrain and hindbrain. Aromatase expression was observed in radial glial cells, revealed by co-localization with the glial marker GFAP and absence of co-localization with the neuronal marker HuC/D. Collectively these results support the idea that brain-derived estradiol in females may serve important functions in reproductive state-dependent physiological and behavioral processes across vertebrates.     

Adiposity and estrogen receptor-positive,postmenopausal breast cancer risk: Quantification of the mediating effects of fasting insulin and free estradiol

Adiposity increases estrogen receptor (ER)-positive postmenopausal breast cancer risk. While mechanisms underlying this relationship are uncertain, dysregulated sex-steroid hormone production and insulin signaling are likely pathways. Our aim was to quantify mediating effects of fasting insulin and free estradiol in the adiposity and ER-positive postmenopausal breast cancer association. We used data from a case–cohort study of sex hormones and insulin signaling nested within the Melbourne Collaborative Cohort Study. Eligible women, at baseline, were not diagnosed with cancer, were postmenopausal, did not use hormone therapy and had no history of diabetes or diabetes medication use. Women with ER-negative disease or breast cancer diagnosis within the first follow-up year were excluded. We analyzed the study as a cumulative sampling case–control study with 149 cases and 1,029 controls. Missing values for insulin and free estradiol were multiply imputed with chained equations. Interventional direct (IDE) and indirect (IIE) effects were estimated using regression-based multiple-mediator approach. For women with body mass index (BMI) >30 kg/m² compared to women with BMI 18.5–25 kg/m², the risk ratio (RR) of breast cancer was 1.75 (95% confidence interval [CI] 1.05–2.91). The estimated IDE (RR) not through the mediators was 1.03 (95% CI 0.43–2.48). Percentage mediated effect through free estradiol was 72% (IIE-RR 1.56; 95% CI 1.11–2.19). There was no evidence for an indirect effect through insulin (IIE-RR 1.12; 95% CI 0.68–1.84; 28% mediated). Our results suggest that circulating free estradiol plays an important mediating role in the adiposity–breast cancer relationship but does not explain all of the association.     

磷脂酰肌醇3激酶抑制剂对17β-雌二醇作用下Ishikawa、HEC-1A细胞增殖和凋亡的影响

目的:观察磷脂酰肌醇3激酶(PI3K)抑制剂LY294002 对17β-雌二醇(E2)作用下子宫内膜癌细胞增殖、凋亡和细胞周期的影响,初步探讨阻断PI3K/Akt通路治疗子宫内膜癌的可能性. 方法:应用MTT法(10-10 mol/L、10-8 mol/L、10-6 mol/L、10-4 mol/L的E2或10-6 mol/L E2及0.1 μmol/L、1 μmol/L、10 μmol/L、50 μmol/L的LY294002)、流式细胞技术(0 mol/L、10-8 mol/L、10-6 mol/L E2或10-6 mol/L E2及0 μmol/L、1 μmol/L、50 μmol/L LY294002)观察LY294002对E2作用下子宫内膜癌细胞Ishikawa、HEC-1A增殖、凋亡和细胞周期的影响.结果:随着E2浓度的增加,Ishikawa细胞A(570 nm)值逐渐升高并呈时间依赖性(F=3.915,P=0.043),G0-G1期比例下降(F=50.926,P≤0.001),S期比例升高(F=17.836,P=0.001);而HEC-1A细胞周期各期比例无变化(P＞0.05).随着 LY294002浓度的增加,2种细胞A(570 nm)值逐渐下降并呈现时间依赖性(F=10.398,P=0.001;F=5.542,P=0.043),而且G0-G1期比例(F=32.024, P≤0.005;F=14.725,P≤0.017)升高,S期(F=30.132, P≤0.001;F=24.72,P≤0.01)比例下降.50 μmol/L和100 μmol/L LY294002作用2种细胞48 h后,凋亡细胞百分比均增加(P＜0.001).结论:LY294002可以抑制E2对子宫内膜癌细胞的增殖,促使其发生凋亡,抑制细胞周期进展,使细胞周期停滞在G1期.PI3K/Akt信号传导通路可作为治疗子宫内膜癌的新靶点.     

Contribution of estrogen receptor subtypes,ERα, ERβ, and GPER1 in rapid estradiol‐mediated enhancement of hippocampal synaptic transmission in mice

Estradiol rapidly modulates hippocampal synaptic plasticity and synaptic transmission; however, the contribution of the various estrogen receptors to rapid changes in synaptic function is unclear. This study examined the effect of estrogen receptor selective agonists on hippocampal synaptic transmission in slices obtained from 3–5‐month‐old wild type (WT), estrogen receptor alpha (ERαKO), and beta (ERβKO) knockout female ovariectomized mice. Hippocampal slices were prepared 10–16 days following ovariectomy and extracellular excitatory postsynaptic field potentials were recorded from CA3‐CA1 synaptic contacts before and following application of 17β‐estradiol‐3‐benzoate (EB, 100 pM), the G‐protein estrogen receptor 1 (GPER1) agonist G1 (100 nM), the ERα selective agonist propyl pyrazole triol (PPT, 100 nM), or the ERβ selective agonist diarylpropionitrile (DPN, 1 µM). Across all groups, EB and G1 increased the synaptic response to a similar extent. Furthermore, prior G1 application occluded the EB‐mediated enhancement of the synaptic response and the GPER1 antagonist, G15 (100 nM), inhibited the enhancement of the synaptic response induced by EB application. We confirmed that the ERα and ERβ selective agonists (PPT and DPN) had effects on synaptic responses specific to animals that expressed the relevant receptor; however, PPT and DPN produced only a small increase in synaptic transmission relative to EB or the GPER1 agonist. We demonstrate that the increase in synaptic transmission is blocked by inhibition of extracellular signal‐regulated kinase (ERK) activity. Furthermore, EB was able to increase ERK activity regardless of genotype. These results suggest that ERK activation and enhancement of synaptic transmission by EB involves multiple estrogen receptor subtypes. © 2015 Wiley Periodicals, Inc.