Impact of Progesterone on Inhibins during Controlled Ovarian Stimulation

Background:To explore the impact of progesterone on inhibins during controlled ovarian stimulation in women with normal ovarian reserve and to compare cycle characteristics and pregnancy outcomes in subsequently frozen-thawed embryo transfer(FET)cycles.Methods:A total of 93 patients were randomly divided into two groups,study group(human menopausal gonadotropin[hMG]+medroxyprogesterone acetate[MPA])and control group(short protocol).Serum hormones were detected on day 3 before ovarian and day 10-12,the trigger day,and the day after trigger(approximately 10 h after trigger).Viable embryos were cryopreserved for later transfer in both protocols.Results:In the study group,inhibins signifcantly increased during ovarian stimulation,and the average inhibins level on the trigger day was signifcantly higher than the basal levels.Inhibin A level increased significantly to 2046.7±1280.5 ng/L after trigger 10 h.Serum inhibin B level slightly decreased at the time of trigger 10 h later compared with the trigger time but did not reach a significant difference.The number of oocytes retrieved in study group was similar to that in control(10.5±4.5 vs.9.0±5.2,P<0.05).No statistically significant differences were found in the clinical pregnancy rate(47.4%vs.52.2%,P<0.05),implantation rate(36.5%vs.36%),and live birth rate(43.4%vs.39.1%,P<0.05)between the two groups.Conclusions:The high level of progesterone did not affect the secretion in granulosa cells during the controlled ovarian stimulation.Therefore,sufficient oocytes/embryos can be obtained by hMG and MPA co-treatment in women undergoing in vitro fertilization/intracytoplasmic sperm injection treatments,with optimal pregnancy outcomes in FET cycles.

Solid-Tubulocystic carcinoma:A new variant of intrahepatic cholangiocarcinoma

A new variant of intrahepatic cholangiocarcinoma(iCCA)has been recognized in recent years presenting predominantly as a large hepatic mass in young woman with the characteristic expression of inhibin by immunohistochemistry.This variant iCCA was originally termed as cholangioblastic variant of iCCA,and subsequently proposed to be renamed as inhibin-positive hepatic carcinoma or solid-tubulocystic variant of iCCA to better reflect its immunohistochemical profile or morphologic spectrum.The tumor histologically is composed of small to medium sized cells with scant to moderate amount of eosinophilic cytoplasm heterogeneously organized in solid,tubular,and cystic growth patterns.The tumor cells are positive for biliary markers,inhibin and albumin,and have a novel recurrent gene fusion,NIPBL::NACC1.Awareness of this new iCCA variant and its clinicopathologic features will aid in the diagnostic work-up and avoid confusion with other primary and metastatic hepatic neoplasms.

CA199、Inhibin A及Vimentin联合检测在卵巢癌鉴别诊断中的应用

目的探讨CA199、Inhibin A及Vimentin联合检测在卵巢癌鉴别诊断中的价值。方法选取123例疑似卵巢癌患者,其中经术后病理确诊为卵巢癌患者74例,卵巢良性病变患者49例。采用酶联免疫吸附法(ELISA)检测所有受试者血清中CA199表达水平,免疫组织化学法检测肿瘤组织中Inhibin A及Vimentin表达情况。以病理诊断结果为金标准,分析各指标单项以及联合诊断卵巢癌效能。结合Logistic回归分析,绘制ROC曲线并计算及比较曲线下面积(AUC)评价各指标单项及联合检测的诊断价值。结果卵巢癌患者血清中CA199水平较卵巢良性病变患者升高(P<0.05),组织中Inhibin A和vimentin阳性表达率较较卵巢良性病变患者升高(P<0.05)。三项联合诊断卵巢癌的灵敏度为93.24%,特异度为87.76%,准确度为91.06%。三项联合检测卵巢癌的灵敏度与准确度均显著高于各单项指标诊断,差异有统计学意义(P<0.05);特异度也均高于各单项指标诊断,但与Vimentin单项诊断相比差异无统计学意义(P>0.05)。CA199、Inhibin A和vimentin单项检测卵巢癌时ROC曲线下面积(AUC)分别为0.782、0.752、0.775,明显低于三者联合检测的ROC曲线下面积0.877(P<0.05)。Logistic回归分析结果显示,CA199、Inhibin A和vimentin均是卵巢癌的独立影响因素。结论联合检测CA199、Inhibin A及vimentin可提高卵巢癌诊断的敏感度及特异性,对卵巢癌诊断有较好的应用价值。

应用组织芯片技术研究A103和Inhibinα在肾上腺皮质腺瘤中的表达

目的 研究 A10 3及 Inhibinα在肾上腺皮质腺瘤中的潜在诊断价值并探讨组织芯片技术应用的可行性。方法 制备肾上腺组织芯片 ,含 79例样本 ,其中正常肾上腺 3例 ,肾上腺皮质腺瘤 66例 ,肾上腺转移癌 5例 ,嗜铬细胞瘤 5例。用免疫组织化学 Envision法检测 A10 3及 Inhibinα的表达。结果 免疫组织化学染色 A10 3阳性率分别为正常肾上腺皮质 10 0 % ( 3 / 3 ) ,肾上腺皮质腺瘤 90 .2 % ( 5 5 / 61) ,肾上腺转移癌 0 % ( 0 / 4) ,嗜铬细胞瘤0 % ( 0 / 4) ;Inhibinα在正常肾上腺皮质中 10 0 %表达 ,阳性部位主要在网状带与束状带内层 ,肾上腺皮质腺瘤阳性率 83 .6% ( 5 1/ 61) ,肾上腺转移癌 0 % ( 0 / 4) ,嗜铬细胞瘤 0 % ( 0 / 4)。结论 A10 3及

Effects of Downregulation of Inhibin α Gene Expression on Apoptosis and Proliferation of Goose Granulosa Cells

Inhibin a is one of the candidate genes that control the ovulation in poultry. To study the genetic effects of inhibin a on apoptosis and proliferation of goose granulosa cells cultured in vitro, two RNA interference （RNAi） expression vectors, psiRNA-INHal and psiRNA-INHα2, were constructed to knock down inhibin α gene expression. After 48 h of transfection, the efficiency of these two RNAi expression vectors was examined by fluorescence microscopy. Meanwhile, inhibin protein expression levels, apoptosis indexes （AI） and proliferation indexes （PI） of granulosa cells were analyzed by flow cytometry. In addition, the supernatants were collected to assay the concentrations of estrogen （E2） and progesterone （P） by radioimmunoassay. The results showed that the expression level of inhibin a in the RNAi group were decreased 30%--40% than those in the control groups （P 〈0.05） and the apoptosis indexes and proliferation indexes in the RNAi groups were significantly higher than those in the control groups （P 〈0.05）. However, the E2 concentrations in the RNAi groups were lower than those in the control groups （P 〈0.05）. These results indicate that inhibin a has antagonistic effect on granulosa cell apoptosis.

Syn、CgA、melan A和inhibin α在肾上腺皮质腺瘤及嗜铬细胞瘤中的表达及意义

目的分析Syn、CgA、melan A和inhibinα在肾上腺皮质腺瘤及肾上腺嗜铬细胞瘤中的表达情况,探讨这组抗体对肾上腺皮质腺瘤及肾上腺嗜铬细胞瘤的诊断与鉴别诊断的意义。方法采用免疫组化方法检测70例肾上腺皮质腺瘤及57例肾上腺嗜铬细胞瘤中Syn、CgA、melan A和inhibinα的表达情况。结果 Syn、CgA、melan A和inhibinα在肾上腺皮质腺瘤中的阳性率分别为87.1%、8.6%、80%和91.4%,而在肾上腺嗜铬细胞瘤中的阳性率分别为91.2%、100%、0和0。结论 Syn、CgA、melan A和inhibinα联合检测对提高肾上腺皮质腺瘤及肾上腺嗜铬细胞瘤的诊断准确性有显著作用。

肾上腺肿瘤中A103、Inhibin α和c-erbB-2的表达

目的 研究A10 3、Inhibinα和c erbB 2在肾上腺肿瘤中的鉴别诊断价值。方法 应用免疫组织化学PowerVisionSys tem法检测 4 8例肾上腺肿瘤A10 3、Inhibinα和c erbB 2的表达。结果 A10 3免疫组化染色阳性率分别为肾上腺皮质腺瘤76 5 % (13/ 17) ,肾上腺皮质腺癌 5 0 0 % (4 / 8)。Inhibinα免疫组化染色阳性率分别为肾上腺皮质腺瘤 82 4 % (14 / 17) ,肾上腺皮质腺癌 75 0 % (6 / 8)。A10 3在肾上腺皮质肿瘤中呈胞质颗粒状阳性 ,主要见于肿瘤的透明细胞区域。Inhibinα呈胞质或胞膜阳性 ,可见于肿瘤的透明细胞和颗粒细胞区域。A10 3和Inhibinα两种抗体在肾上腺皮质腺瘤表达率 94 1% (16 / 17) ,在肾上腺皮质腺癌表达率为 87 5 % (7/ 8)。A10 3和Inhibinα在肾上腺嗜铬细胞瘤均呈阴性表达。c erbB 2表达率 :肾上腺皮质肿瘤为 6 4 0 % (16 / 2 5 ) ,肾上腺嗜铬细胞瘤为 17 4 % (4 / 2 3)。c erbB 2呈胞质颗粒状或弥漫阳性。在所有肿瘤中未观察到特异性的胞膜阳性反应。结论 A10

Melan-A和Inhibin α在肾上腺肿瘤鉴别诊断中的作用

目的 研究Melan A和Inhibinα在肾上腺肿瘤鉴别诊断中的作用。方法 78例肿瘤组织标本 ,包括 5例正常或瘤旁肾上腺组织、17例肾上腺皮质腺瘤、8例肾上腺皮质腺癌、2 3例肾上腺嗜铬细胞瘤、13例肝细胞癌和 12例肾细胞癌。应用PowerVisionTMSystem法检测Melan A和Inhibinα的表达。结果 Melan A在正常或瘤旁肾上腺组织表达阳性率 10 0 % ,肾上腺皮质腺瘤 76 5 % ,肾上腺皮质腺癌 5 0 %。在肝细胞癌和肾细胞癌中均呈阴性表达。In hibinα在正常或瘤旁肾上腺组织表达阳性率 10 0 % ,肾上腺皮质腺瘤 82 4 % ,肾上腺皮质腺癌 75 0 %。Inhibinα在肝细胞癌表达率 2 3 1% ,肾细胞癌 16 7% ,肾上腺嗜铬细胞瘤呈阴性表达。结论 Melan

孕中期检测血清AFP、Free-β-hCG和inhibin-A产前筛查的临床价值

目的探讨孕中期血清标记物甲胎蛋白（AFP）、游离β-人绒毛膜促性腺激素（Free—β—hCG）和抑制素A（inhibin—A）在产前筛查的实用价值。方法对3728例孕14～20周的孕妇分别采用化学发光法和酶联免疫方法检测血清AFP、Free—β—hCG和inhibin—A浓度，通过训‘算机软件计算危险系数，对高风险率孕妇进行遗传咨询，在知情同意的情况下进行羊水细胞染色体的产前检查。结果在3728例孕妇中筛查出唐氏综合征、β-三体及神经管缺损高危孕妇163例，占筛查总数的4．37％。91例进一步确诊，共检出先天缺陷7例，检出率为7．69％。结论孕中期血清中AFP、Free—β—hCG和inhibin—A用于产前筛查能早期发现和诊断胎儿先天缺陷，对降低其出生率是有效的，可以应用于临床大范围人群的产前筛查。

肾上腺皮质腺瘤组织中Calretinin、Melan-A和Inhibin α的表达及意义

目的探讨Calretinin、Melan-A和Inhibinα在肾上腺皮质腺瘤(ACA)组织中的表达及意义。方法采用免疫组化Max Vision两步法检测30例ACA、4例肾上腺皮质结节状增生、30例肾上腺良性嗜铬细胞瘤(ABP)、8例正常肾上腺组织中Calretinin、Melan-A和Inhibinα的表达。结果 Calretinin阳性率:ACA70.0%、肾上腺皮质结节状增生100.0%、ABP 13.4%、正常肾上腺皮质75.0%、正常肾上腺髓质0.0%;Melan-A阳性率:ACA 53.3%、肾上腺皮质结节状增生50.0%、ABP 3.3%、正常肾上腺皮质25.0%、正常肾上腺髓质0.0%;Inhibinα阳性率:ACA 83.3%、肾上腺皮质结节状增生100.0%、ABP 6.7%、正常肾上腺皮质100.0%、正常肾上腺髓质0.0%。Calretinin、Melan-A和Inhibinα在ACA组织中的表达显著高于ABP,差异有统计学意义(0.05)。三者或两两联合检测敏感性最高的是Calretinin与Inhibinα(76.7%)、特异性最高的是Melan-A与Inhibinα(95.0%)、准确性最高的是Calretinin与Inhibinα(83.3%)。结论 Calretinin、Melan-A和Inhibinα联合检测在ACA的诊断及其与ABP的鉴别诊断中具有重要价值。

颈部颗粒细胞瘤1例

颗粒细胞瘤（granular cell tumor,GCT）于1926年首先由Abrikossoff[1]描述,是一种少见的良性肿瘤,恶变率约占3%[2]。目前GCT病因尚不明确,可发生于全身任何部位,以舌部最为常见。其临床表现多为单发性无痛肿块,也有多发及家族易感性相关研究[3]。现将我科收治的颈部颗粒细胞瘤1例进行报道如下。

Cloning and Sequence Analysis of 5′ Flanking Region and Exon of Inhibin α Precursor Gene in Goats

[Objective] The aim of this study was to reveal the relationship between inihibin （INH） α precursor gene and seasonal reproduction of goats, and investigate the evolutionary conservation of INHα precursor gene. [ Method] Cloning and sequence analysis of 5＇ flanking region and exon of inihibinα （INHE） precursor gene in twenty ewes between non-seasonal estrous breed （Haimen goats） and seasonal estrous breed （Anhui white goats） was analyzed in this study. [ Result] Compared with Anhui white goats, INHα precursor gene in Haimen goats had three SNP but no amino acid change, while its nucleotide homology was 99.7% and amino acid homology was 100%. The nucleotide homology of INHα precursor gene in goat, cattle, pig, person, chicken, horse, rat and dog ranged from 12.7% to 96.5%. [ Conclusion] INHα precursor gene tends to be highly conserved in species, and any change of nucleotide and amino acid maybe directly influence the function of the whole gene coding and regulation.

抑制素在反刍动物繁殖中的应用研究

抑制素(inhibin,INH)主要是由卵巢颗粒细胞和睾丸支持细胞分泌的糖蛋白类激素,在生理状况下,对雌性动物可选择性地抑制垂体合成和促卵泡素(FSH)分泌,从而影响卵巢上卵泡的发育和成熟;对雄性动物的作用表现为抑制精子的发生,降低睾丸的生精能力,是调节家畜繁殖力的主要生殖激素之一。目前对哺乳动物INH的来源、分子结构及生理作用已有较深入的认识,INH也得到了更广泛的应用。

卵巢上皮性癌中inhibin及其受体β-glycan的表达

目的探讨α-inhibin及其受体β-glycan在恶性卵巢上皮性肿瘤中的表达,评估两种多肽信号对卵巢癌生长的调控作用,探讨卵巢癌的发病机制。方法应用EliVision方法检测30例正常卵巢组织、30例卵巢囊腺瘤和80例卵巢囊腺癌中α-in-hibin及其受体β-glycan的表达。结果α-inhibin在正常卵巢、卵巢囊腺瘤和卵巢囊腺癌中的总阳性表达率分别为93.3%、60.0%、36.3%,差异均有显著性(P<0.01);β-glycan在正常卵巢、卵巢囊腺瘤、卵巢囊腺癌的阳性表达率呈逐渐下降的趋势分别为100%、80.0%、75.0%,卵巢囊腺瘤、囊腺癌与正常卵巢组比较,差异有显著性(P<0.05),但卵巢囊腺瘤与囊腺癌比较,差异无显著性(P>0.05)。结论α-inhibin蛋白在卵巢囊腺癌中表达明显下降,而β-glycan在卵巢肿瘤中的表达仍然很高,提示β-glycan对增强α-inhibin抑制卵巢囊腺癌的形成可能起着一定的作用。

抑制素(Inhibin)基因免疫在提高动物繁殖力中的应用

抑制素(Inhibin)是一种由性腺器官分泌的糖蛋白激素,能抑制垂体促卵泡素(FSH)的分泌及卵泡发育。本文主要阐述抑制素基因免疫对动物繁殖力的影响及影响免疫效果的因素。

Can inhibin-B predict the outcome of microsurgical epididymal sperm aspiration in patients with suspected primary obstructive azoospermia？

Aim： To evaluate whether inhibin-B can predict the outcome of a microsurgical epidymal sperm aspiration （MESA） procedure in patients with suspected primary obstructive azoospermia （OA） and if inhibin-B can replace testicular biopsy in the diagnostic work-up of these patients. Methods： Inhibin-B levels and testicular biopsy scores were related to the outcome of MESA in 43 patients with suspected primary OA. MESA was considered to be successful when epididymal sperm could be identified during the procedure. Results： Spermatozoa were present in the epididymal aspirate in 28 out of the 43 patients （65%）. lnhibin-B values were not significantly different in patients with successful or unsuccessful MESA. The modified Johnsen score, however, was significantly lower in patients with unsuccessful MESA （P = 0.003）. A rete testis obstruction or epididymal malfunctioning was found in 15% of patients with suspected primary OA, reflected by unsuccessful MESA despite normal inhibin-B levels and normal testicular histology. Conclusion： Inhibin-B cannot replace testicular biopsy as a diagnostic tool in the work-up of patients with suspected primary OA. Testicular biopsy is useful in identifying patients with spermatogenic arrest, who might have normal inhibin-B values.

Effects of Immunization Against Inhibin on Egg-Laying Performance in Magang and Landaise Geese

This study aimed to improve egg-laying performance in incubating Magang geese of Guangdong origin and Landaise geese of French origin. In experiment 1, 50 adults, egg-laying Magang geese were inoculated intramuscularly （i.m.） on days 0, 22, and 45 with 1 mL of immunogen containing 1 mg of recombinant chicken inhibin fusion protein. Immunization significantly increased blood antibody titers against inhibin fusion protein, but did not affect the egg-laying performance within 10 days after the first inoculation. From day 15, the egg-laying rate in inhibin-immunized group increased and was significantly higher than the values of control geese from day 40 to 55. However, the reverse was true from day 55 to 75 when more immunized geese developed incubation. In the entire 120 days of the experiment, the immunized geese laid 17.3 eggs in contrast to 16.4 eggs laid by the control geese. From day 30 till the end of the experiment, weight of eggs in the control geese was significantly greater than that in inhibin-immunized birds. In experiment 2, 40 Landaise geese were immunized against inhibin, as described in experiment 1. These geese laid 9.0 eggs on average in contrast to 7.3 eggs laid by nonimmunized control geese over 90 days of egg laying. The above results demonstrated that immunization against recombinant chicken inhibin fusion protein improved egg-laying performance in geese, and the increment was higher in nonincubating geese.

Effect of Inhibinα(1-32)Gene Immunization on the Follicular Development and Reproductive Hormones in Rats

A total of 40 rats, aged in 30 days. were divided into 4 groups and immunized (intramuscularly injection) with 0 μg(control), 15μg (group 1), 25μg (group 2) or 40 μg (group 3) of inhibin α(1-32) re-combinant expression plasmid pcINH in combination with liposome. Booster was given without liposome on day 20 after primary immunization. The results showed that 50%(13/26) rats were detected in positive antibody against inhibin. However, the increase of immunization dosage and booster did not promote the ratio of antibody positive rats. The number of matured follicles above 0.8 mm in diameter in the antibody positive rats was 2.3 more than that in the negative rats (P>0. 05). The concentration of blood plasma FSH increased distinctively on day 10 after primary immunization (P<0. 05), but no increase was observed after booster immunization. The 17-β-estradiol levels in blood plasma of rats between the positive and the negative groups had no remarkable differences (P>0.05). These results suggested that recombinant inhibin expression plasmid could stimulate animal body to produce antibody against inhibin.

Endocrine and ovarian responses in water buffalo cows immunized against inhibin and subjected to the Ovsynch protocol

The aim of this study was to investigate the feasibility of stimulating ovarian fol icle development in order to improve fertility in water buffalo cows by immunization against inhibin. The experiment was carried out in early summer (May) and included 24 multi-parity crossbred Murrah-Swamp buffaloes that were divided into immunized (n=11) and control (n=13) groups. Each immunized cow was administered with a 2-mL immunogen of mineral oil adjuvant containing 2 mg of recombinant inhibinα-subunit fusion protein. The controls were treated with the adjuvant only. Al animals received Ovsynch protocol treatment, starting on the day of the antigen administration, and they were artiifcial y inseminated upon behavioral estrus. As a result, al of the immunized buffaloes generated antibodies against inhibin during the experimental period and had higher plasma concentrations of fol icle-stimulating hormone (FSH), activin, and estradiol (E2) related to estrous expression. A higher proportion of immunized animals expressed estrus behavior than did the controls (72%vs. 30%, P<0.05). On aver-age, inhibin-immunized buffaloes had signiifcantly more large fol icles (≥9 mm in diameter) than the controls (mean±SEM;1.2±0.1 vs. 0.84±0.1, respectively;P<0.05) and a slightly higher mean total number of fol icles (≥2 mm;11.4±0.7 vs. 9.0±1.1, respectively;P=0.09) and smal (2–4 mm) fol icles (8.81±0.6 vs. 6.84±1.0, respectively;P=0.12). A higher percentage of cows ovulated in the immunized group than in the control group (91%(10/11) vs. 54%(7/13), respectively;P<0.05). Moreover, inhibin-immunized cows had slightly larger corpus luteum (CL) than the controls 9 days after ovulation and signiifcantly higher (P<0.01) post-ovulation peak plasma progesterone (P4) concentrations. Immunization against inhibin also mar-ginal y increased the conception rate 42 days after insemination (45.8%vs. 15.4%;P>0.05). These results demonstrate that immunization against inhibin, coupled with the treatment with the Ovsynch protocol, can constitute a new technique to increase fertility in water buffalo cows.

Clinical Value of Serum Anti-Mullerian Hormone and Inhibin B in Prediction of Ovarian Response in Patients with Polycystic Ovary Syndrome

The present study aimed to investigate the clinical value of serum anti-mullerian hormone（AMH） and inhibin B（INHB） in predicting the ovarian response of patients with polycystic ovary syndrome（PCOS）. A total of 120 PCOS patients were enrolled and divided into three groups in terms of the ovarian response： a low-response group（n=36）, a normal-response group（n=44）, and a high-response group（n=40）. The serum AMH and INHB levels were measured by enzyme-linked immunosorbent assay（ELISA）. The follicle stimulating hormone（FSH）, luteinizing hormone（LH）, and estradiol（E2） levels were determined by chemiluminescence microparticle immunoassay. The correlation of the serum AMH and INHB levels with other indicators was analyzed. A receiver operating characteristic（ROC） curve was established to analyze the prediction of ovarian response by AMH and INHB. The results showed that there were significant differences in age, body mass index（BMI）, FSH, total gonadotropin-releasing hormone（Gn RH）, LH, E2, and antral follicle counts（AFCs） between the groups（P〈0.05）. The serum AMH and INHB levels were increased significantly with the ovarian response of PCOS patients increasing（P〈0.05）. The serum AMH and INHB levels were negatively correlated with the age, BMI, FSH level, Gn, and E2 levels（P〈0.05）. They were positively correlated with the LH levels and AFCs（P〈0.05）. ROC curve analysis of serum AMH and INHB in prediction of a low ovarian response showed that the area under the ROC curve（AUC） value of the serum AMH level was 0.817, with a cut-off value of 1.29 ng/m L. The sensitivity and specificity were 71.2% and 79.6%, respectively. The AUC value of serum INHB was 0.674, with a cut-off value of 38.65 ng/m L, and the sensitivity and specificity were 50.7% and 74.5%, respectively. ROC curve analysis showed when the serum AMH and INHB levels were used to predict a high ovarian response, the AUC value of the serum AMH level was 0.742, with a cut-off value of 2.84 ng/m L, and the sensitivity and specificity were 72.7% and 65.9%, respectively; the AUC value of the serum INHB level was 0.551 with a cut-off of 45.76 ng/m L, and the sensitivity and specificity were 76.3% and 40.2%, respectively. It was suggested the serum AMH and INHB levels have high clinical value in predicting the ovarian response of PCOS patients.