Apoptosis and apoptosis-related proteins (Fas, Fas ligand, Blc-2, p53) in lymphoid elements of human ovarian tumors

Different types of lymphocytes have different roles in tumor suppression. Thus, their expression of apoptosis-related proteins (ARP - Fas and Fas ligand, bcl-2, p53) in lymphocytes and their apoptosis were analyzed immunohistochemically in ovarian tumors of different grades. Ovaries without oncologic disorders had few lymphocytes, mainly T cells, and no ARP. Benign cysts presented features of weak immune reaction: small lymphoid infiltration and few lymphocytes. The ARP were present in 13.7% to 23.5% of the lymphocytes, and apoptosis was rare. In borderline tumors, expansion of lymphoid infiltrates and increased density of lymphocytes resulted in a tenfold rise in total lymphocytes, reflecting intensification of the immune response. Most lymphocytes were T cells (92%) predominated by CD8+ cells that were in direct contact with tumor epithelial cells. ARP species were found in 47% to 65% of the lymphocytes, and apoptosis in 2.2%. In carcinomas with ligh lymphoid infiltration, lymphocytes were 2.5 times more abundant, and the apoptotic index as well as the number of CD20+ and CD25+ lymphocytes rose sharply, whereas bcl-2 positive lymphocytes decreased to 8% of their number in borderline tumors. In carcinomas with low lymphoid infiltration, the total lymphocyte count decreased eightfold compared to carcinomas with high lymphoid infiltration, reflecting the deep subcompensation of the lymphoid system. Few p53-positive lymphocytes were found in the carcinomas. In conclusion, we found a positive correlation between apoptosis and the numbers of CD4+ or CD8+ lymphocytes in epithelial ovarian tumors. This correlation could reflect the antitumor activity of T cells. However, the high expression of ARP studied by immune cells at the vicinity of the tumor ARP reveals the lymphoid vulnerability to apoptosis, resulting in devastation of the lymphoid tissue, and consequently in tumor progression.     

卵巢早衰患者外周血CD4~+CD25~+Treg细胞的变化及意义

目的:探讨CD4+CD25+调节性T细胞(即CD4+CD25+Treg细胞)在卵巢早衰发病机制中的作用。方法:流式细胞仪定量检测卵巢早衰(premature ovarian failure,POF)患者、卵巢储备功能下降(diminished ovarian reserve,DOR)患者及健康对照组外周血CD4+T、CD8+T细胞及CD4+CD25+Treg细胞数量,应用3H-thymidine掺入法测定POF患者及对照组外周血CD4+CD25+Treg细胞对效应性T细胞的增殖抑制功能。结果:与对照组相比,POF患者及DOR患者CD4+CD25+Treg细胞比例降低(P<0.01)、POF患者CD4+T/CD8+T细胞比值增高(P<0.05),DOR患者CD4+T/CD8+T细胞比值无明显变化(P>0.05);POF患者免疫抑制功能无明显降低(P>0.05)。结论:CD4+CD25+Treg细胞比例降低与T细胞亚群失衡可能是POF的发病机制。     

脱氢表雄酮在卵巢储备功能低下高龄患者体外受精/卵胞质内单精子注射-胚胎移植中的应用研究

目的探讨口服脱氢表雄酮(DHEA)辅助治疗在卵巢储备功能低下(DOR)高龄患者体外受精/卵胞质内单精子显微注射-胚胎移植(IVF/ICSI-ET)中的临床疗效。方法选取行IVF/ICSI助孕治疗的DOR患者152例,所有患者均行2次及以上助孕周期,前一周期为未加用药周期(治疗前组),本次为用药周期(治疗后组),进行自身用药前后对照分析。比较口服DHEA后卵巢储备功能的变化情况,同时比较是否加用DEHA患者IVF/ICSI-ET的临床治疗参数、实验室参数及临床结局。结果 (1)口服DHEA后患者血清抗苗勒管激素(AMH)、硫酸脱氢表雄酮(DHEA-s)、睾酮(T)及窦卵泡计数(AFC)较用药前升高,卵泡刺激素(FSH)较前下降,差异有统计学意义(P0.05);(2)治疗后组h CG注射日E2及孕酮(P)水平、获卵数、受精率、可移植胚胎数、胚胎种植率及临床妊娠率高于治疗前组,Gn总用量、Gn使用时间、周期取消率低于治疗前组,差异有统计学意义(P0.05)。结论 DOR的高龄患者在进入IVF/ICSI周期前口服DHEA可改善其卵巢储备功能及助孕结局。     

Significant differences of lymphocytes isolated from ascites of patients with ovarian cancer compared to blood and tumor lymphocytes. Association of CD3+CD56+ cells with platinum resistance

OBJECTIVES: Tumor infiltrating lymphocytes (TILs) and T regulatory cells (Tregs) have been associated with prognosis in ovarian cancer, but their prognostic significance in ascites has not been studied. We performed a prospective study of T lymphocytes isolated from ascites from patients with ovarian carcinoma and we compared them with the respective populations in blood and tumors. METHODS: Mononuclear cells from ascites (n=71) and blood were isolated by Ficoll, while tumor lymphocytes (n=20) were obtained upon mechanical dissociation. Phenotypic analysis was performed with flow cytometry. Ascites from 10 patients with cirrhosis was used as control. RESULTS: Tregs containing CD4(+)CD25(+) cells, NK-T containing CD3(+)CD56(+) cells and CD69 and HLADR expression of CD4 and CD8 lymphocytes were significantly increased in tumor ascites compared to blood and control ascites. A selective accumulation of these populations in the ascites of cancer patients, was suggested by the significantly higher ascites/blood (A/B) ratios in cancer patients but not controls. Cancer cell content in ascites was correlated with CD4(+)CD25(+), CD4(+)CD69(+), CD4(+)HLADR(+) and CD8(+)CD69(+) cells. There was no correlation of lymphocyte populations between ascites and samples from peritoneal metastases. Higher tumor grade was associated with increased A/B CD4(+)CD25(+) ratio and reduced CD3(+)CD56(+) cells, while platinum resistance was associated with reduced A/B CD3(+)CD56(+) ratio. CONCLUSIONS: There are significant differences of CD3(+)CD56(+) and CD25(+)CD4(+) lymphocytes and increase in lymphocyte activation between blood, ascites and peritoneal metastases from patients with ovarian cancer. The selective accumulation of CD3(+)CD56(+) population in ascites may be a predictive factor for platinum resistance.     

Induction of ovarian tumor-specific CD8+ cytotoxic T lymphocytes by acid-eluted peptide-pulsed autologous dendritic cells

OBJECTIVE: To evaluate the potential of dendritic cells pulsed with acid-eluted peptides derived from autologous ovarian cancer cells for eliciting a tumor-specific cytotoxic T cell response in women with advanced ovarian cancer. METHODS: CD8+ T lymphocytes derived from peripheral blood mononuclear cells stimulated in vitro with autologous ovarian tumor peptide-pulsed dendritic cells were tested for their ability to induce an HLA class I-restricted cytotoxic T lymphocyte response against autologous tumor cells. To correlate cytotoxic activity by cytotoxic T lymphocytes with T cell phenotype, we used two-color flow cytometric analysis of surface markers and intracellular cytokine expression (interferon-gamma versus interleukin-4). RESULTS: CD8+ cytotoxic T lymphocyte responses against autologous ovarian tumor cells were elicited in three consecutive women who had advanced ovarian cancer. Although cytotoxic T lymphocyte populations from all women expressed strong cytolytic activity against autologous tumor cells, they did not lyse autologous lymphoblasts or Epstein-Barr virus-transformed cell lines, and they showed negligible cytotoxicity against the natural killer-sensitive cell line K-562. Cytotoxicity against the autologous tumor cells was significantly inhibited by anti-HLA class I (W6/32) and anti-HLA-A2 (BB7-2) monoclonal antibodies. CD8+ cytotoxic T lymphocytes expressed variable levels of CD56 and preferentially expressed interferon-gamma rather than interleukin-4. CONCLUSIONS: Peptide-pulsed dendritic cells induced specific CD8+ cytotoxic T lymphocytes that killed autologous tumor cells from women with advanced ovarian cancer. This finding might contribute to the development of active or adoptive immunotherapy for residual or resistant ovarian cancer after standard surgery and cytotoxic treatment.     

Update on the use of dehydroepiandrosterone supplementation among women with diminished ovarian function

Objective We assessed the role of DHEA supplementation on pregnancy rates in women with diminished ovarian function. Design This is a case control study of 190 women with diminished ovarian function. The study group includes 89 patients who used supplementation with 75 mg daily of oral, micronized DHEA for up to 4 months prior to entry into in vitro fertilization (IVF). The control group is composed of 101 couples who received infertility treatment, but did not use DHEA. The primary outcome was clinical pregnancy after the patient’s initial visit. We developed a Cox proportional hazards model to compare the proportional hazards of pregnancy among women using DHEA with the controls group. Results Cumulative clinical pregnancy rates were significantly higher in the study group (25 pregnancies; 28.4% vs. 11 pregnancies; 11.9%; relative hazard of pregnancy in study group (HR 3.8; 95% CI 1.2–11.8; p < 0.05). Conclusions DHEA treatment resulted in significantly higher cumulative pregnancy rates. These data support a beneficial effect of DHEA supplementation among women with diminished ovarian function. DB and NG are signatories on a pending patent application which claims a beneficial benefit for dehydroepiandrosterone supplementation on ovarian function.     

Immunologic studies in patients with premature ovarian failure

Tests for a range of autoantibodies, and counts of lymphocytes, B cells, T cells, and T cell subsets were performed in 45 Chinese patients with premature ovarian failure and 45 age-matched normal control subjects. Eight patients (18%) were positive for at least one autoantibody. Only one patient was positive for antiovarian antibody. Patients with autoantibodies had a significantly higher percentage of circulating B cells. The lymphocyte, T cell, CD4+, and CD8+ counts in patients with premature ovarian failure were significantly higher than those in the control group, but the CD4:CD8 ratio was significantly lower in women with premature ovarian failure. There was a significant negative correlation between plasma estradiol levels and CD8+ counts, and a significant positive correlation between plasma estradiol levels and CD4:CD8 ratios. The changes in lymphocytes and lymphocyte subpopulations in premature ovarian failure may be due to estrogen deficiency.     

Ovarian cysts in women with inflammatory bowel disease

The frequency of ovarian cysts in patients with Crohn's disease (CD) or ulcerative colitis (UC) is believed to be higher than in the normal population, but this aspect has not been studied hitherto. The prevalence of ovarian cysts in the normal population is unknown. By ultrasonic scanning, we studied the frequency of ovarian cysts in 61 patients with CD, 64 with UC, and in 100 controls. The findings were positive in 3 out of 61 with CD, 5 of 64 with UC, and in 2 of 100 controls. There is a tendency to a higher frequency of ovarian cysts in patients with inflammatory bowel diseases than in the normal population, but no statistically significant difference.     

Preliminary study of hormone determinations during aminoglutethimide therapy for advanced breast cancer

The aim of this study is to report on Aminoglutethimide-induced hormonal modifications in advanced breast cancer. Estradiol (E2), Testosterone (T), Dehydroepiandrosterone sulphate (DHEA(s] and Aldosterone (A) were determined before, and once every two weeks during treatment with Aminoglutethimide plus Hydrocortisone in 13 menopausal women with advanced breast cancer. The patients were selected either for their E2 and P4-receptor-positive in the original tumor or in metastases or by presenting objective clinical improvement to prior endocrine treatment. On the basis of the response to treatment the patients may be classified in two groups: 1) responders (n = 7) and 2) non-responders. No significant modifications of T concentrations were obtained in group 1 until after the first 8 months of treatment. One spontaneous menopausal patient with a T basal value of 0.80 ng/ml was evaluated during 12 months of treatment. From month 8, T diminished to values below 0.30 ng/ml, indicating a direct action of Aminoglutethimide, hydrocortisone or both drugs on ovarian steroidogenesis. The results obtained from the remaining hormonal parameters, evaluated in all the cases beginning from the second week of treatment, remained unchanged throughout the entire period of study. They were as follows: 1) E2 diminished with respect to basal values between 36 and 60%, thus confirming Aminoglutethimide inhibitory effect upon peripheral aromatization; 2) DHEA(s) diminished between 80 and 90%, indicating an adrenal inhibition due to the combined effect of both drugs, and 3) Aldosterone diminished to values between 80 and 110 pg/ml, these values being within the normal lower range.(ABSTRACT TRUNCATED AT 250 WORDS)     

Response of a mucinous ovarian tumor of borderline malignancy to human chorionic gonadotropin

Plasma and urinary steroid hormones were measured before and after an injection of human chorionic gonadotropin (hCG) to a postmenopausal woman with a mucinous ovarian tumor of borderline malignancy. Hormones were also measured in blood from a vein draining the tumor, and circulating gonadotropins and plasma and urinary steroids were measured before and after tumor removal. Baseline levels of plasma progesterone (P), androstenedione (delta 4 A), and estradiol (E2), and urinary estrogens and pregnanediol were high; they increased dramatically in response to hCG and fell after tumor removal. A less striking increase in testosterone, dihydrotestosterone, dehydroepiandrosterone (DHEA), and DHEA sulfate was noted after hCG injection. A gradient existed between tumor vein and peripheral vein levels of P, 17 alpha-hydroxyprogesterone, delta 4 A, E2, DHEA, and cortisol. Plasma follicle-stimulating and luteinizing hormones initially low but rose to the postmenopausal range after surgery. These results indicate the presence of delta 4 and delta 5 androstene pathways within the tumor. The responsiveness of the tumor to hCG provides further evidence that hCG may be the endogenous stimulus to steroid hormone production by epithelial ovarian tumors.     

脱氢表雄酮(DHEA)预治疗在体外受精-胚胎移植周期中的应用

目的:探讨脱氢表雄酮(DHEA)预治疗在卵巢储备低下妇女的体外受精/卵胞质内单精子注射-胚胎移植(IVF/ICSI-ET)周期治疗中的作用。方法:对173例卵巢储备功能低下进行IVF/ICSI-ET的患者进行随机对照研究。DHEA预治疗组(n=81)患者口服DHEA,连用3个月,对照组为未服用DHEA预治疗者(n=92)。观察患者的一般情况、超促排卵情况及胚胎发育和妊娠结局。结果:患者一般情况、hCG注射日子宫内膜厚度及E2水平、Gn使用量和Gn使用天数组间均无统计学差异(P>0.05)。DHEA组IVF受精率、优质胚胎率及临床妊娠率均高于对照组(P<0.05)。但在胚胎种植率、早期流产率、周期取消率组间差异无统计学意义(P>0.05)。结论:DHEA预治疗可以改善卵巢储备功能低下妇女的IVF结局。     

Significance of matrix metalloproteinases in the pathophysiology of the ovary and uterus

Matrix metalloproteinases (MMP) are capable of degrading a variety of extracellular matrix (ECM) proteins and are also involved in the processing of a number of bioactive molecules. Our findings indicate that the functions of MMP in the ovary and uterus are organ-specific and time-dependently vary during the reproductive cycle. Prolactin induces structural luteolysis indicated by loss of luteal weight, protein and DNA within 36 h after pretreatment with ergot alkaloid. MMP activation appears crucial for the selective depletion of protein during luteal involution, which entails loss of ECM accompanied by apoptosis. During GnRHagonist-induced luteolysis, this response was also associated with marked increases in MMP-2, which degraded collagen type IV, and MT1-MMP, which in addition to activating MMP-2 also degrades collagen type I, III and V. We also found that the level of MT1-MMP and MMP-2 expression in the human CL is greater during the late luteal phase than during either the early mid luteal phases or during gestation, respectively. That dehydroepiandrosterone (DHEA) treatment caused the formation of cysts from antral follicles in the ovaries of immature rats while depressing MMP-2 collagenolytic activity and enhancing lysyl oxidase expression highlights the importance of collagen degradation in the process of ovulation and suggests that changes in the activities of these enzymes play a key role in ovarian cystogenesis in polycystic ovary syndrome patients. Furthermore, immunohistochemical analyses showed that MT1-MMP and FasL co-localize with TdT-mediated dUTP-biotin nick endlabeling (TUNEL)-positive apoptotic granulosa cells in rats treated with DHEA, that the Fas/FasL/Caspase-8 (death receptor-dependent) pathway is pivotal for follicular atresia and that increased levels of MT1-MMP likely play an important role in tissue remodeling during follicular atresia. After parturition, the uterus undergoes involution, a conspicuous feature characterized by a rapid reduction in the collagen content mediated by degradation of extracellular collagen bundles. Our findings strongly suggest that MT1-MMP, MMP-2 and MMP-9 are each time-dependently regulated and play important roles in tissue remodeling during postpartum uterine involution.     

卵巢癌患者自体细胞因子诱导杀伤细胞治疗前后免疫功能的检测与分析

目的观察卵巢癌患者自体细胞因子诱导杀伤细胞治疗前后患者外周血淋巴细胞亚群的变化,为综合评价临床应用CIK细胞疗法治疗卵巢癌的效果提供依据。方法2004-2005采集中国医科大学附属第一医院5例卵巢癌患者的外周血单个核细胞,经多种细胞因子诱导制成CIK细胞,回输前及回输后取患者外周血,流式细胞仪测定外周血淋巴细胞亚群的变化。结果诱导培养后,CD3+/CD56+效应细胞的比例明显升高;CIK细胞回输后患者外周血CD3+、CD3+/CD8+、CD3+/CD56+阳性淋巴细胞亚群的比例明显升高。结论CIK细胞疗法可以提高卵巢癌患者的细胞免疫功能,提高对肿瘤细胞的杀伤作用。     

复发性流产患者外周血T淋巴细胞亚群及CD4^＋辅助性T淋巴细胞亚型的变化

】     

6B11ScFv-mHSP70融合蛋白诱导抗卵巢癌免疫应答的体外实验研究

目的 既往研究证实,6B11抗独特型单链抗体（6B11ScFv）具有模拟卵巢癌相关抗原OC166-9的作用。本文研究6B11ScFv与小鼠热休克蛋白70（mHSP70）构建而成的融合蛋白（6B11ScFv-mHSP70）在体外抗卵巢癌免疫应答,探讨其作为卵巢癌疫苗的可能性。方法 以大肠杆菌表达6B11ScFv-mHSP70融合蛋白,经变性复性后纯度达95%。采用ELISA检测其免疫学活性。采集HLA-A2阳性的女性健康志愿者的外周血单个核细胞,用6B11ScFv-mHSP70刺激并培养。采用CCK-8法、LDH释放法分别观察淋巴细胞增殖情况和对卵巢癌细胞系的细胞毒作用,流式细胞术检测6B11ScFv-mHSP70刺激前后淋巴细胞表型的改变。结果 6B11ScFv-mHSP70具有特异性结合卵巢癌单抗COC166-9及抗小鼠-HSP70抗体的双重免疫学活性;可以刺激人外周血淋巴细胞的增殖;并对HLA-A2阳性、OC166-9表达阳性的卵巢癌细胞系有细胞毒作用;经6B11ScFv-mHSP70刺激后,实验组的淋巴细胞表型与未经蛋白刺激的对照组相比：CD4＋T细胞明显增加,CD8＋T细胞略有增加。CD4＋/CD8＋的比率明显增加,CD4＋CD25＋T细胞占CD4＋T细胞的比率明显下降,差异有统计学意义。结论 6B11ScFv-mHSP70融合蛋白在体外可诱导特异性抗卵巢癌的细胞免疫反应,有可能作为抗独特型疫苗用于卵巢癌的主动免疫。     

Ovarian and adrenal contributions to peripheral steroid levels in postmenopausal women.

Serum levels of cortisol (F), pregnenolone (delta5-P), 17-hydroxypregnenolone (17-delta5-P), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), progesterone (P), 17-hydroxyprogesterone (17-P), androstenedione (A), testosterone (T), dihydrotestosterone (DHT), androst-5-ene-3beta, 17beta-diol (delta5-diol), estrone (E1), and estradiol-17beta (E2) were measured in 10 postmenopausal and 5 premenopausal women before (control) and after 7 days of Dexamethasone (post-dex). Control and post-dex levels of delta5-P, P, DHT, T, and F were not different (P greater than 0.05) in premenopausal versus postmenopausal women, while the control levels of 17-P, DHEA, DHEA-S, A, delta5-diol, and E2 were lower in the postmenopausal women (P less than 0.05). Assuming post-dex levels equal ovarian contribution, the ovarian contribution of 17-delta5-P, 17-P, DHEA, delta5-diol, A, E1, and E2 and the adrenal contribution (control-post-dex) to DHEA, DHEA-S, 17-P, A, and delta5-diol was significantly lower (P less than 0.05) in postmenopausal subjects.     

Dehydroepiandrosterone supplementation improves predictive markers for diminished ovarian reserve: serum AMH,inhibin B and antral follicle count

Objective

To evaluate the effect of dehydroepiandrosterone (DHEA) supplementation on ovarian reserve by measuring markers such as antral follicle count, serum anti-Müllerian hormone (AMH) and inhibin B in patients with diminished ovarian reserve.

Study design

This prospective study was undertaken at Dr. Zekai Tahir Burak Women's Health Research and Education Hospital, Ankara, Turkey. Forty-one patients with diminished ovarian reserve were included in the study and received supplementation with DHEA 25 mg, t.i.d., for at least 6 weeks. Serum AMH, inhibin B, follicle-stimulating hormone (FSH) and oestradiol, and antral follicle count were determined before and after DHEA supplementation. Baseline ovarian reserve parameters such as antral follicle count, FSH, oestradiol, AMH, inhibin B, clinical and laboratory IVF outcomes, and pregnancy rates were studied.

Results

There were significant differences in day 3 FSH, oestradiol, antral follicle count, AMH and inhibin B levels before and after DHEA supplementation in all patients (p = 0.001, 0.001, 0.002, 0.001 and 0.001, respectively). The study population was divided into two age groups (<35 and ≥35 years) to determine whether there was a difference in the effect of DHEA supplementation between younger and older patients with diminished ovarian reserve. Significant differences were found in all of the parameters in both study groups (p < 0.05).

Conclusions

DHEA supplementation is an effective option for patients with diminished ovarian reserve. Prior to assisted reproductive technology, patients with diminished ovarian reserve should be offered DHEA supplementation as an alternative to oocyte donation.     

Butyrylcholinesterase activity and lymphocyte subpopulations in peripheral blood of Kuwaiti women experiencing recurrent spontaneous abortion

This study has evaluated the hypothesis that activity of the detoxifying enzyme butyrylcholinesterase (BuChE) correlates with levels of serum anti-cardiolipin antibodies (ACA) and T lymphocytes in peripheral blood of women experiencing recurrent spontaneous abortion (RSA). Peripheral venous blood from 16 non-pregnant, RSA-afflicted women and 8 healthy non-pregnant women was analyzed for frequency of T lymphocyte subpopulations by two-color flow cytometry and for serum BuChE using butyrylthiocholine iodide/spectrophotometry. RSA-afflicted women with high serum ACA, but not those with normal ACA levels, exhibited significantly increased percentages of CD4+CD25+ cells (p<0.01) and CD4+HLA-DR+ cells (p<0.05) relative to healthy women. CD4+CD25+(high) cells were significantly lower (p<0.05), while CD4+CD25+(low) cells were significantly higher (p<0.01), in women with elevated ACA compared to healthy women and to RSA women with normal ACA. Relative to healthy, non-pregnant subjects, serum BuChE activity in RSA patients was elevated, both for those with normal ACA (p<0.001) and elevated ACA levels (p<0.01). Among healthy controls, a significant positive correlation was observed between frequency of CD3+NK cells and BuChE activity (p<0.01), but not for RSA-afflicted subjects. A positive correlation between BuChE activity and frequency of CD4+CD25+ cells, as well as CD4+CD25+(high) cells, was observed in the RSA-afflicted subject group with elevated ACA (p<0.05), which may be related to induction of BuChE by toxic metabolites resulting from pathogenic T cell activity. It is concluded that, among RSA patients, high serum ACA correlates with elevated levels of activated T cells and reduced CD4+CD25+(high)/CD4+CD25+(low) cells in comparison to healthy women or those afflicted with RSA but with normal ACA. BuChE activity is observed to be elevated in RSA patients irrespective of serum ACA status.     

Activated (HLA-DR) T-Lymphocyte Subsets in Early Epithelial Ovarian Cancer and Malignant Ovarian Germ Cell Tumors

We examined peripheral blood T-lymphocyte subsets before initiation of therapy in 79 healthy controls, 3 patients with endometriosis, 95 patients with common epithelial tumors of the ovary, 15 patients with ovarian germ cell tumors, and 3 patients with ovarian sex cord-stromal tumors. In stage Ia/Ib patients with epithelial ovarian cancer, the percentages of activated CD4⁺ (CD4⁺HLA-DR⁺) T cells and activated CD4+ T cells in the CD4⁺ T-cell subsets were significantly higher than those of healthy controls and patients with benign or borderline epithelial tumors of the ovary. These immonologic parameters were subsequently decreased in patients in stage Ic and more advanced stages. In malignant ovarian germ cell tumors, a similar increase in the CD4⁺ T-cell subsets was observed. Moreover, the percentage of activated CD8⁺ T cells in the CD8⁺ T-cell subsets in stage Ia/Ib patients increased significantly compared with those in healthy controls and patients with benign tumors. Our findings indicate that activated T lymphocytes may play some roles in oncogenesis and progression of both epithelial ovarian cancer and malignant ovarian germ cell tumors.     

Effects of dehydroepiandrosterone supplementation on mice with diminished ovarian reserve

Dehydroepiandrosterone (DHEA) has been used to improve the pregnancy rate in women with diminished ovarian reserve(DOR) during in vitro fertilization. We aimed to validate the effects of DHEA and identify the possible mechanisms. We constructed a mice model with DOR and analyzed the hormone parameters and follicle counts. In vivo experiment, FSH and LH concentrations in the serum were significantly elevated in the DOR group. However, the FSH and LH concentrations were partially reversed in the DOR?+?DHEA group. The E2, AMH and INHB were down-regulated in the DOR group and reversed in the DOR?+?DHEA group. Our study supported evidences that DHEA might modulate the hormone receptors in the ovary and hormone secretions to the peripheral circulation to regulate the ovary reserve functions.