消炎痛抑制兔排卵的最适时间

早已知道消炎痛可抑制哺乳类动物的排卵,为了研究给与消炎痛抑制排卵的最适时间进行以下实验.用绒毛膜促性腺激素(HCG)50IU/kg使免排卵,在排卵前10小时到排卵后9小时内间隔一定时间给消炎痛,剂量从1.25～40mg/kg.实验动物在给HCG以后的20～24小时内(即正常排卵后的10～14小时)剖腹,取出卵巢在解剖显微镜下检查并记录破裂的卵泡数.在100只兔中随机取样,平均每     

含消炎痛IUD对家兔子宫内膜影响的酶组织化学观察

本文采用酶组织化学方法观察了含消炎痛IUD对家兔子宫内膜几种酶的影响,并与全铜、硅胶及铜加消炎痛IUD进行了比较.结果表明:(1)含消炎痛IUD组子宫内膜NSE、SDII和ATPase三种酶活性增强;全铜IUD组则上述三种酶活性明显下降;加消炎痛的含铜IUD组子宫内膜酶活性低于含消炎痛IUD组,但高于硅胶对照组.(2)全铜IUD组子宫内膜损伤较明显.由此可见,含消炎痛IUD对子宫内膜上皮功能及结构的损害均小于含铜IUD.     

在卵泡破裂中前列腺素的双重调节机理

关于前列腺素在排卵中作用,虽然已得到实验证明,但在卵泡破裂中的作用尚未弄清。为了明确前列腺素在卵泡破裂中的作用机理,应用前列腺素合成抑制剂消炎痛(indomethacin),研究各种条件下对幼鼠诱发排卵反应的影响。对22日龄的幼鼠先皮下注射孕马血清促性腺激素5 U,56小时后静脉注射人绒毛膜促性腺激素10U。在18小时后计算输卵管内的卵子数,以平均排卵数来评价排卵反应。结果如下: (1)各种剂量的消炎痛与人绒毛膜促性腺激素同时给予时,平均排卵数随用量增加而减少,消炎痛给予90μg以上时排卵反应完全抑制。 (2)以上法得知消炎痛最小有效量为90μg,     

去甲肾上腺素诱发离体的大鼠下丘脑LHRH和垂体LH的释放

1947年Sawyer等首先指出α-肾上腺素能受体阻断剂dibenamine能抑制兔排卵,并提出去甲肾上腺素(NE)与黄体生成素(LH)释放有关。随后有许多研究者报告过α-肾上腺素能受体阻断剂或去甲肾上腺素合成抑制剂也能抑制大鼠排卵和/或LH峰的出现。近来有人更进一步证明在大鼠第三脑室注射NE可诱发排卵和促性腺激素的释放。1970至1971年Kamberi等曾设想NE引起促性腺激素释放的效应可能并非直接作用于垂体前叶,而是通过丘脑下部释放的LHRH间接作用来实现。作者在本文中采用离体序列双室灌流系统检测了NE对丘脑下部中央基底部黄体生成素释放激素(LHRH)的释放和黄体生成素(LH)由垂体释放的影响。     

前列腺素与排卵

1972年报道消炎痛等前列腺素(PGs)合成阻断剂抑制大白鼠排卵之后才知道PGs参与排卵机构。其后报道许多实验结果,PGs对排卵过程所起的作用,特别是以卵泡破裂为中心。兹就LH波峰出现起至卵泡破裂过程中PGs怎样参与排卵作一综述。一、促性腺激素分泌与PGs和白三烯(LTs) Kaur等将消炎痛向大白鼠中枢神经系     

应用腹腔内窥术观察甲地孕酮对非人炅长类排卵的影响

甲地孕酮抗生育的作用有人认为主要是由于对宫颈粘液和内膜的局部作用而引起的,也有人认为对精子获能、受精和配子的运行有作用。本文描述了应用腹腔镜观察两种非人灵长类经皮下注射或埋植甲地孕酮后的卵巢,证明了这一技术在避孕机理研究中的价值。作者选用了35只雌松鼠猴和7只猕猴,麻醉下进行腹腔镜观察。发现松鼠猴皮下注射甲地孕酮50微克/天无抑制排卵作用,500微克/天完全阻止排卵,猕猴注射500微克/天不能有效地抑制排卵。松鼠猴皮下埋植甲地孕酮后其排卵率与埋植时间成反比,在给FSH前11天埋植其排卵率为63%,相反在给FSH前29天埋植其排卵率为33%。测定了20个埋植物的体内释放率为平均56.2±2.8微克/天。10个埋植物的体外释放率平均12.6±1.7微克/天。~3H标记的埋植物在体内保持5周后测其在组织中的分布,药物浓度在输卵管和卵巢内含量最高,     

消炎痛缓释系统的释放特性与子宫相容性的初步研究

将消炎痛参入加温硫化型硅胶橡,制成均质型消炎痛释放系统,其消炎痛释放维持时间与消炎痛参入量有关。含6.4%与16%消炎痛的释放维持时间分别约为140天与378天。将含6.4%与16%消炎痛及空白释放装置植入大鼠子宫内30天或45天后,子宫组织学检查未见明显的损伤性变化。     

促性腺素释放素拮抗剂在体外受精-胚胎移植中的LH峰抑制

目的:探讨促性腺素释放素拮抗剂(GnRHA)在体外受精-胚胎移植(IVF-ET)中应用的效果。方法:回顾性分析使用GnRHA方案的306个IVF-ET周期(实验组)和使用常规促性腺素释放素激动剂(GnRHa)长方案266个IVF-ET周期(对照组)。结果:实验组Gn用量少于对照组,但无显著性差异;GnRHA用药时间明显少于GnRHa;实验组平均获卵数、中、重度OHSS发生率明显低于对照组;优质胚胎移植率明显高于对照组。而二组受精率、卵裂率、优质胚胎移植率、胚胎冷冻率、种植率、妊娠率均无统计学差异。二组均无LH峰提早出现。结论:GnRHA为我们提供了一种安全的控制性超排卵方案,并可有效抑制LH峰过早出现。     

甾体避孕药对某些疾病的治疗作用

口服避孕药问世40多年来，临床科技人员对其进行了大量的观察与研究。这些研究证明，口服避孕药除具有确切的避孕效果外，还具有对某些疾病的治疗作用，这与避孕药抑制排卵和调整周期有关。事实上，口服避孕药已经对功能失调性子宫出血、痛经、高雄激素血症性相关性疾病、子宫内膜异位症等疾病进行了治疗，对某些妇科疾病有较好的疗效。     

消炎痛抑制狨猴的排卵

在啮齿类动物中已研究证明,消炎痛可抑制前列腺素的合成,从而阻断了黄体生成激素的诱发排卵作用。本文研究目的是确定在灵长类狨猴中消炎痛对排卵、黄体形成和黄体酮产生的影响。以35只成年雌狨作为研究对象,实验前隔离3～4周。对照组19只狨用人类绝经期促性腺激素(HMG)50国际单位肌肉注射,连续6天,于第7天用人类绒毛膜促性腺激素(HCG)500国际单位肌肉注射以诱发排卵,于第8(3只),9(12只),10天(4只)分别杀死,抽心血用放射免疫法测定黄体酮水平,取卵巢做病理检查。治疗组16只狨猴用消炎痛10毫克肌肉注射1次/日,从用HMG第三天起持续到实验     

Significance of fibrinolysis in ovulation

To elucidate the significance of fibrinolytic enzymes in ovulation, the changes in the levels of plasminogen activator, plasminogen and plasmin activity were examined using prepubertal rats and sows treated with PMS and hCG. The following results were obtained. 1) The superovulation in rats was blocked with antifibrinolytic agents. 2) Plasminogen and plasminogen activator in the supernatant of rat ovarian homogenates increased toward ovulation. But plasmin activity did not show the significant change. 3) When the superovulation of the rats was blocked with indomethacin, plasminogen remained constant, but plasminogen activator was almost affected. 4) In the supernatant of follicle wall homogenates and the follicular fluid of sows, plasminogen decreased, but plasmin activity increased toward ovulation. 5) Plasminogen activator was produced by rat ovarian granulosa cells, but hCG, gonadotropins, prostaglandins and indomethacin did not activate the production of plasminogen activator in the granulosa cells.     

Inhibition of ovulation in marmoset monkeys by indomethacin.

The effect of indomethacin on human menopausal gonadotropin/human chorionic gonadotropin-induced ovulation was studied in marmoset monkeys. Indomethacin was effective in preventing follicular rupture and ovum extrusion when administered simultaneously with gonadotropin. The production of progesterone and luteinization of the granulosa cells were not affected by indomethacin treatment. Histologic examination of corpora lutea from indomethacin-treated animals revealed the presence of entrapped oocytes surrounded by luteal cells. These results suggest that prostaglandin synthesis is required for ovulation in this species, but not for luteinization and progesterone production.     

Collagenolytic enzyme activity in human ovary: an ovulatory enzyme system

Collagenolytic enzyme activities presumed to play an important role in ovulation were investigated in the human follicular apex, base, and granulosa cell layer throughout the ovarian cycle. Those analyzed were human ovarian collagenase, 2,4-dinitrophenyl-Pro-Gln-Gly-Ile-Ala-Gly-Gln-D-Arg-OH peptidase, N-carbobenzoxy-Gly-Pro-Gly-Gly-Pro-Ala peptidase, and alpha-N-benzoyl-DL-arginine beta-naphthylamide hydrolase. Collagenase activity was also measured in human granulosa cell cultures. The activities of all four enzymes showed a marked preovulatory decrease in the apex. The activities in the apex were slightly higher than those in the base throughout the ovarian cycle. However, the activities in the granulosa cell layer and collagenase activity in the granulosa cell cultures increased toward preovulation and decreased after ovulation. These findings suggest that collagenase is synthesized in the granulosa cells maximally at preovulation and is consumed in the follicular apex at the same time, resulting in collagen degradation and disruption of the follicular wall in collaboration with other collagenolytic enzymes investigated here.     

A histochemical study of the respiratory system in rabbit ovarian follicles during ovulation

Histochemical studies on the activities of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), succinate dehydrogenase (SDH) and cytochrome oxidase (CY-O) in rabbit ovarian follicles at various times after the administration of hCG were performed to investigate the relationship between the activities of steroid biosynthesis and the respiratory system. The activities of 3 beta-HSD and SDH were studied by using the tetrazolium salt and CY-O activities by the method of Seligman with prefixation. On the granulosa cell layer prior to the administration of hCG, no activities of 3 beta-HSD and CY-O were detectable, while slight activities of SDH were observed. These three enzymes showed intense activities on the granulosa cell layer 3 hours after the administration of hCG, which were maintained till the time of ovulation. The results indicated that increased activities of steroid biosynthesis in the granulosa cell layer after LH-surge were accompanied by the accelerated TCA cycle and respiratory chain. Energy from accelerated glycolysis may be utilized for steroid biosynthesis in preovulatory granulosa cells. Increased O2 consumption due to accelerated aerobic glycolysis is in accordance with hyperactivity of perifollicular capillaries, which finally leads to rapid follicular expansion and ovulation.     

Roles of epidermal growth factor (EGF)-like factor in the ovulation process

Luteinizing hormone (LH) surge stimulates preovulatory follicles to induce the ovulation process, including oocyte maturation, cumulus expansion, and granulosa cell luteinization. The matured oocytes surrounded by an expanded cumulus cell layer are released from follicles to the oviduct. However, LH receptors are dominantly expressed in granulosa cells, but less in cumulus cells and are not expressed in oocytes, indicating that the secondary factors expressed and secreted from LH-stimulated granulosa cells are required for the induction of the ovulation process. Prostaglandin and progesterone are well-known factors that are produced in granulosa cells and then stimulate in both granulosa and cumulus cells. The mutant mice of prostaglandin synthase (Ptgs2KO mice) or progesterone receptor (PRKO mice) revealed that the functions were essential to accomplish the ovulation process, but not to induce the ovulation process. To identify the factors initiating the transfer of the stimuli of LH surge from granulosa cells to cumulus cells, M. Conti’s lab and our group performed microarray analysis of granulosa cells and identified the epidermal growth factor (EGF)-like factor, amphiregulin (AREG), epiregulin (EREG), and β-cellulin (BTC) that act on EGF receptor (EGFR) and then induce the ERK1/2 and Ca²⁺-PLC pathways in cumulus cells. When each of the pathways was down-regulated using a pharmacological approach or gene targeting study, the induction of cumulus expansion and oocyte maturation were dramatically suppressed, indicating that both pathways are inducers of the ovulation process. However, an in vitro culture study also revealed that the EGFR-induced unphysiological activation of PKC in cumulus cells accelerated oocyte maturation with low cytostatic activity. Thus, the matured oocytes are not arrested at the metaphase II (MII) stage and then spontaneously form pronuclei. The expression of another type of EGF-like factor, neuregulin 1 (NRG1), that does not act on EGFR, but selectively binds to ErbB3 is observed in granulosa cells after the LH surge. NRG1 supports EGFR-induced ERK1/2 phosphorylation, but reduces PKC activity to physiological level in the cumulus cells, which delays the timing of meiotic maturation of oocytes to adjust the timing of ovulation. Thus, both types of EGF-like factor are rapidly induced by LH surge and then stimulate cumulus cells to control ERK1/2 and PKC pathways, which results in the release of matured oocytes with a fertilization competence.     

Human ovarian surface epithelial cells are capable of physically restructuring extracellular matrix.

OBJECTIVE: After ovulation the human ovarian surface epithelium proliferates at the wound edges, migrates over the ovulatory defect, and contributes to its repair primarily by the action of proteolytic enzymes and by the deposition of new matrix material. We examined the potential for human ovarian surface epithelial cells to physically remodel extracellular matrix in culture, similar to collagen gel lattice contraction by fibroblasts, a well-known culture model for wound repair, as an additional role of human ovarian surface epithelium in wound repair. STUDY DESIGN: Human ovarian surface epithelium cells from ovarian biopsies of 11 patients were grown in culture and plated onto a combination of collagen gel and rat ovarian surface epithelial-derived extracellular matrix. The degree of matrix contraction was measured as the percentage of the original culture diameter. RESULTS: Human ovarian surface epithelial cells surrounded and contracted the combination of matrices into a dense matrix organoid. The degree of organoid contraction was related to the number of human ovarian surface epithelial cells plated per organoid and to the inclusion of fibroblasts within the collagen gel but was not affected either by adding epidermal growth factor and hydrocortisone to the culture medium or by reducing the serum component of the medium. CONCLUSION: Human ovarian surface epithelial organoids may be useful for the study of normal and abnormal ovarian events such as ovulatory wound repair and cyst formation.     

Laminin and fibronectin concentrations of the follicular fluid correlate with granulosa cell luteinization and oocyte quality

Background and Aims :  Progesterone production of human cultured luteinizing granulosa cells was reported to be modified by extracellular matrix, suggesting that extracellular matrix regulates luteinization of granulosa cells after ovulation. In the present study, the relationship among laminin, fibronectin, progesterone and estradiol in follicular fluid along with oocyte quality was analyzed to estimate the physiological role of extracellular matrix in follicular luteinization and oocyte quality during ovulation.
Methods and Results :  Follicular fluid was collected at oocyte pick-up from the patients undergoing in vitro fertilization treatment and intracytoplasmic sperm injection. The concentrations of laminin, fibronectin, progesterone and estradiol in the follicular fluid were measured by enzyme immunoassay and radioimmunoassay. The morphology of oocytes were also assessed during the procedure of intracytoplasmic sperm injection and was classified into normal and abnormal groups. The fibronectin concentration was higher in the normal ooplasm group than in the abnormal group, but it did not correlate with estradiol or progesterone concentration. However, laminin concentration significantly correlated with that of progesterone, but not with cytoplasm morphology of oocytes. There was no difference in estradiol or progesterone concentration between the normal and abnormal groups.
Conclusion :  These findings suggest that extracellular matrix plays some roles in regulating human granulosa cell luteinization and oocyte quality during ovulation. (Reprod Med Biol 2004; 3 : 43–49)     

Surface ultrastructure of polycystic ovaries as viewed by electron microscopy

Scanning electron microscopy was used to observe surface fine structure of germinal epithelium and granulosa cells of human ovaries from 24 patients with polycystic ovaries and primary infertility. Synthetic LH-RH was administered intravenously and serum LH was measured at frequent intervals before and after LH-RH injection. The PCO patients were arbitrarily classified into two groups on the basis of ovarian morphology: typical PCO (Type I) with greater LH response than the lower LH response of a typical PCO (Type II). The germinal epithelium which did not completely cover the surface of the normal ovary was characterized by patchy areas of cells with and without dense microvilli. In normal preovulatory follicles, most granulosa cells were polyhedral in shape with smooth surfaces, whereas those facing the follicular cavity were elongated and flattened and were covered with material having a filamentous/reticular texture. In PCO the germinal epithelium surrounding the whole surface possessed dense microvilli, solitary cilia, and blebs, resembling the fetal ovary. In normal ovaries, the follicular cells were uniform in size and shape with microvilli and evaginations. The PCO cells have irregular size and shape with few microvilli.     

Extracellular matrix of the cumulus-oocyte complex

The mammalian oocyte is surrounded by several layers of cumulus granulosa cells that nurture the oocyte during its development and actively participate in the process of ovulation. After the ovulatory luteinizing hormone surge, a distinctive program of extracellular matrix production is initiated in the cumulus-oocyte complex. This process known as cumulus expansion or mucification involves synthesis of a backbone of long hyaluronan oligosaccharide chains that are cross-linked by a complex of hyaluronan binding cell surface and extracellular matrix proteins and proteoglycans. Active components of the cumulus matrix are synthesized directly by cumulus cells under the control of endocrine- and oocyte-derived factors, secreted by mural granulosa cells, or enter the follicle in blood plasma. Appropriate composition and assembly of the cumulus matrix is essential for ovulation, efficient passage of the oocyte through the oviduct, and for fertilization. This review describes the critical components and their functional roles in the cumulus matrix, as well as the molecular regulation of cumulus matrix gene expression.     

Effects of ovulation induction agents on ovarian surface epithelium in rats

The aim of this study was to examine the effects of ovulation induction agents on the ovarian surface epithelium in rats. Sixty adult females were randomly divided into six groups, each containing 10 rats. In four of these groups ovulation induction was applied with six cycles of clomiphene citrate, human menopausal gonadotrophin (HMG), recombinant FSH (rFSH) or human chorionic gonadotrophin (HCG), respectively, followed by unilateral oophorectomy, and another six cycles of the same treatment. After a total of 12 cycles of ovulation induction, the remaining ovary was taken out and the alterations in ovarian surface epithelium were examined. No malignancies were observed on the ovarian surface epithelium of the rats that were given clomiphene citrate, rFSH or HMG as ovulation induction agents, while identification rates of histopathological parameters constituting epithelial dysplasia were found to be significant (P < 0.05). There was no significant dysplasia in the epithelium of the group which was given HCG only, relative to control groups. The findings suggest that the ovulation induction agents except for HCG bring about dysplasia in the ovarian surface epithelium. It is not clear whether these dysplasias are precursory lesions of ovarian malignancies.