BACKGROUND Large-cell neuroendocrine carcinoma(NEC)is an uncommon type of tumor that can occur in the endometrium.This aggressive cancer requires definitive management.Here,we describe the clinical characteristics and...BACKGROUND Large-cell neuroendocrine carcinoma(NEC)is an uncommon type of tumor that can occur in the endometrium.This aggressive cancer requires definitive management.Here,we describe the clinical characteristics and treatment of a postmenopausal woman with large cell NEC of the endometrium.CASE SUMMARY A 55-year-old Asian female presented with a 1-year history of postmenopausal vaginal bleeding.Transvaginal ultrasound revealed a thickened endometrium(30.2 mm)and a hypervascular tumor.Computed tomography revealed that the tumor had invaded more than half of the myometrium and spread to the pelvic lymph nodes.The tumor marker,carcinoembryonic antigen,was elevated(3.65 ng/mL).Endocervical biopsy revealed high-grade endometrial carcinoma.She underwent radical hysterectomy,bilateral salpingo-oophorectomy,omentectomy,and bilateral pelvic and para-aortic lymph node dissection.Pathological examination revealed mixed neuroendocrine and endometrioid adenocarcinoma,pT2N0M0,grade 3,and International Federation of Gynecology and Obstetrics stage 2.Immunohistochemistry showed moderate estrogen and progesterone receptor expressions(20%and 1%,respectively),focal CD56 expression(NEC marker),positive staining for vimentin,p53(wild type),and ki67(90%),and loss of expression of PMS2(Lynch syndrome marker).The patient received five cycles of cisplatin and etoposide after surgery.No recurrence was noted after 5 mo.CONCLUSION We report the characteristics and successful management of a rare case of large cell endometrial NEC concomitant with Lynch syndrome.展开更多
Background: Recent studies have revealed that noncoding RNAs play important regulatory roles in the formation of endometrial receptivity.Circular RNAs(circRNAs) are a universally expressed noncoding RNA species that h...Background: Recent studies have revealed that noncoding RNAs play important regulatory roles in the formation of endometrial receptivity.Circular RNAs(circRNAs) are a universally expressed noncoding RNA species that have been recently proposed to act as miRNA sponges that directly regulate expression of target genes or parental genes.Results: We used Illumina Solexa technology to analyze the expression profiles of circRNAs in the endometrium from three goats at gestational day 5(pre-receptive endometrium,PE) and three goats at gestational day 15(receptive endometrium,RE).Overall,21,813 circRNAs were identified,of which 5,925 circRNAs were specific to the RE and 9,078 were specific to the PE,which suggested high stage-specificity.Further analysis found 334 differentially expressed circRNAs in the RE compared with PE(P < 0.05).The analysis of the circRNA-miRNA interaction network further supported the idea that circRNAs act as miRNA sponges to regulate gene expression.Moreover,some circRNAs were regulated by estrogen(E2)/progesterone(P4) in endometrial epithelium cell lines(EECs) and endometrial stromal cell line(ESCs),and each circRNA molecule exhibited unique regulation characteristics with respect to E2 and P4.Conclusions: These data provide an endometrium circRNA expression atlas corresponding to the biology of the goat receptive endometrium during embryo implantation.展开更多
Endometrial development is a complicated process involving numerous regulatory factors.Circular RNAs(circRNAs)have been known as a member of the naturally occurring non-coding RNA family,and are reportedly crucial for...Endometrial development is a complicated process involving numerous regulatory factors.Circular RNAs(circRNAs)have been known as a member of the naturally occurring non-coding RNA family,and are reportedly crucial for a variety of physiological processes.This study investigated the circRNA landscape of non-pregnant endometrium of dairy goats during estrus.Non-pregnant endometrial samples of goats at estrus day 5(Ed5)and estrus day 15(Ed15)were used to methodically analyze the circRNA landscape using strand-specific Ribo-Zero RNA-Seq.A total of 2331 differentially expressed(P<0.05)circRNAs(DEciRs)between Ed5 and Ed15 were discovered in the goat endometrium.It was found that Nipped-B-like(NIPBL)and calcium responsive transcription factor(CARF)may participate in the development of the endometrium by decreasing(P<0.05)the levels of their circRNA-transcript forms.Furthermore,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses of DEciR host genes(hgDEciRs)revealed that tight junctions and GTPases may be involved in endometrial development during the estrus cycle.A total of 2331 DEciRs were discovered in the endometrium at Ed5 and Ed15.Based on GO and KEGG enrichment analyses,it could be inferred that tight junctions and GTPases are likely to play an important role in the development of goat endometrium during the estrus cycle.This circRNA study greatly enhances our knowledge of global trends in the development of non-pregnant endometrium during the estrus cycle in goats;these results help us to better understand the molecular regulation of endometrial development in dairy goats.展开更多
The activity of matrix metalloproteinases (MMPs) in the uterine flushing and endometrial tissue of normal adult women wearing FCu IUD (fixed Cu IUD) or FICu IUD (indomethacin releasing FCu IUD) was observed by using z...The activity of matrix metalloproteinases (MMPs) in the uterine flushing and endometrial tissue of normal adult women wearing FCu IUD (fixed Cu IUD) or FICu IUD (indomethacin releasing FCu IUD) was observed by using zymography on SDS PAGE containing gelatin. The results showed that the activity and kinds of MMPs in FCu IUD group were increased significantly as compared with themselves before being inserted FCu IUD. However, compared with the FCu IUD group, the activity of some kinds of MMPs in the FICu IUD group was decreased significantly. These data suggest that IUD can enhance the activity of MMPs in human endometrium, intermediated by prostaglandins, and MMPs may have relation to IUD induced menorrhagia and indomethacin reduces IUD induced menorrhagia by partly inhibiting MMPs synthesis.展开更多
Background:Endometriosis can lead to infertility.Since there is no definitive treat-ment for endometriosis,animal modelling seems necessary to examine the possible treatments.Mouse endometrium cannot be separated for ...Background:Endometriosis can lead to infertility.Since there is no definitive treat-ment for endometriosis,animal modelling seems necessary to examine the possible treatments.Mouse endometrium cannot be separated for endometriosis induc-tion.In addition,transplantation of uterus into the abdominal viscera to induce endometriosis causes organ damage.In this study,we defined a new model of en-dometriosis leading to separability of endometrium and a safe anatomical region for transplantation.Methods:Forty female mice were allocated to 5 groups:1,sham;2,allograft uterus transplantation of mice to anterior abdominal wall of mice;3,allograft uterus trans-plantation of mice to mesentery of mice;4,xenograft endometrial transplantation of rat to anterior abdominal wall of mice;5,xenograft endometrial transplantation of rat to mesentery of mice.Adult female rats with a previous pregnancy experience were selected and placed in the vicinity of male rats for 2 weeks to induce estrogen secre-tion and increase endometrial thickness.Results:In the 4th group of animals,compared to sham,the peritoneal concentrations of VEGF-A,TNF-α,NO,MDA,and serum levels of CA-125 and IL-37 were increased and total body weight was decreased,while weight and size of endometrial lesions were increased significantly(P<.05).Genes expression of HOXA10 and HOXA11 were decreased significantly(P<.05)in groups 2 and 4 compared to sham.Conclusions:Xenograft transplantation of endometrium from rat to anterior abdomi-nal wall of mice can potentially mimic human endometriosis morphologically,histo-logically,and genetically.展开更多
Objective:The aim of this study was to determine the expression of Hoxa 10 in endometrium during the menstrual cycle and their response to sex steroids and HB-EGF.Methods:Forty endometrial samples from regularly cycli...Objective:The aim of this study was to determine the expression of Hoxa 10 in endometrium during the menstrual cycle and their response to sex steroids and HB-EGF.Methods:Forty endometrial samples from regularly cycling women were studied.The endometrial epithelial(EEC)and stromal(ESC)cells isolated by collagenase Ⅰ digestion and mechanical dissociation was cultured from every sample.The endometrial stromal cells(ESC)were incubated with 17-beta estradiol(10-8mol/L),medroxyprogesterone acetate(MPA)(10-6mol/L),RU486(10-8mol/L)or HB-EGF(10ng/ml)for 48 hours respectively.The expression of Hoxa10 mRNA was demonstrated by reverse transcription-polymerase chain reaction(RT-PCR).Result:Hoxa10 showed a regulated cycle phase-dependent expression pattern in stromal cells and epithelial cells.Hoxa10 expression dramatically increased during the midsecretory phase of the menstrual cycle,at the time of implantation.The expression of Hoxa10 in cultured endometrial stromal cells was stimulated by estrogen,progesterone and HB-EGF.Conclusion:The cycle phase-specific expression of Hoxa10 and up-regulated by sex steroids and HB-EGF suggests a tight regulation and establishing conditions necessary for implantation.展开更多
BACKGROUND Postmenopausal bleeding and an endometrial thickness≥5 mm on sonograms of menopausal women can indicate the presence of endometrial lesions.Diagnostic hysteroscopy is a powerful method for endometrial dise...BACKGROUND Postmenopausal bleeding and an endometrial thickness≥5 mm on sonograms of menopausal women can indicate the presence of endometrial lesions.Diagnostic hysteroscopy is a powerful method for endometrial diseases.AIM To investigate the pathological pattern of endometrial abnormalities in postmenopausal women with bleeding or asymptomatic thickened endometrium diagnosed by hysteroscopy.METHODS A total of 187 postmenopausal women with bleeding or asymptomatic thickened endometrium underwent diagnostic hysteroscopy.The women were subsequently divided into three groups:Postmenopausal bleeding(PMB)group(n=84),asymptomatic group(n=94),and additional group(n=9).Women in the additional group manifested abdominal pain and leukorrhagia.RESULTS Among the 187 patients examined,84(44.9%)were diagnosed with PMB and 94(50.3%)with asymptomatic thickened endometrium.Endometrial polyp was the most common endometrial abnormality,which was detected in 51.2%,76.6%and 77.8%of the PMB,asymptomatic,and additional groups,respectively.In the PMB group,7(8.3%)women had hyperplasia with atypia and 14(16.7%)had endometrial adenocarcinoma.Fewer malignant lesions were detected in the asymptomatic group.Endometrial hyperplasia without atypia was found in 8.3%of the PMB group and 7.4%of the asymptomatic group.CONCLUSION Endometrial polyp was the most common pathology in the PMB group.Diagnostic hysteroscopy is recommended for women with PMB and asymptomatic thickened endometrium.展开更多
Pathogenesis of the endometriosis is complex and the etiology is still unclear. The objective of this study was to examine that endometrial gene expression in late secretory phase endometrium differs between patients ...Pathogenesis of the endometriosis is complex and the etiology is still unclear. The objective of this study was to examine that endometrial gene expression in late secretory phase endometrium differs between patients with and without endometriosis. Five patients with proven advanced-stage endometriosis and 5 controls underwent endometrial biopsy in the late secretory phase. Analysis of eutopic endometrial gene expression was performed using Affymetrix gene arrays and differentially expressed genes were assigned to gene ontology groups based on overrepresented analysis using Database for Annotation, Visualization, and Integrated Discovery software. Four hundred sixty two genes were identified as up-regulated such as matrix metalloproteinase 10, cytochrome P450 family 24 subfamily A polypeptide 1, matrix metalloproteinase 3, chemokine (C-C motif) ligand 20, Rho family GTPase 1, interleukin 1-beta, and insulin-like growth factor binding protein 1. Six hundred forty three genes were down-regulated in all endometriotic samples. A lot of genes related with metabolic process, cellular ketone metabolic process and ncRNA metabolic processing were included. Expression patterns of selected five genes were validated by quantitative real time PCR. The results of this analysis support that the eutopic endometrium from patients with advanced-stage endometriosis has distinct gene expression profile from eutopic endometrium of control without endometriosis.展开更多
The role of the tumor necrosis factor (TNF) system in endometriosis is not completely clear and therefore was the focus of this study. In eutopic endometria obtained from women with (n = 41) and without (controls;n = ...The role of the tumor necrosis factor (TNF) system in endometriosis is not completely clear and therefore was the focus of this study. In eutopic endometria obtained from women with (n = 41) and without (controls;n = 34) endometriosis during laparoscopy, the subcellular location and the percentages for TNF, TNFR1, TNFR2 and CD45 positive-cells were determined (immunohistochemistry);the protein concentration (ELISA) of the soluble receptors (sTNFR1 and sTNFR2) were measured in 4h-explants culture media and the TNF concentration was performed in ex vivo endometrial homogenates. The TNF, TNFR1 and TNFR2 mRNAs were analyzed by real-time PCR. In control endometria, TNF, TNFR1 and sTNFR1 proteins increased during the late secretory phase. In endometriosis endometria, the protein highest level of TNFR1 was reached during the early and the mid secretory phases and of sTNFR1 concentration during the proliferative phase;however, during the late secretory phase, both TNFR1 and sTNFR1 protein levels were reduced compared to the control endometria (p sTNFR2 concentrations, and TNF and TNFR2 mRNAs were similar in control and endometriosis endometria. Although TNFR1 mRNA was highly expressed, no significant differences were found between control and endometriosis endometria. In summary, this study establishes that TNF and TNFR1 protein expressions and the sTNFR concentrations in eutopic endometria from women with and without endometriosis are dependent on the menstrual cycle. The differences on the TNFR1 and sTNFR1 protein pattern between both groups, mainly during the mid and late secretory phases may play a role in the lower implantation rates observed in women with endometriosis, and also could be related to the altered cell death, which favor the augmented cell viability facilitating the characteristic endometrial implantation and growth outside the uterus in this disease.展开更多
Objectives: We try to demonstrate the expression of vascular endothelial growthfactor (VEGF) and its receptors, flt-1 and KDR, in normal human emdometrium duringthe menstrual cycle.Methods: Immunohistochemical method ...Objectives: We try to demonstrate the expression of vascular endothelial growthfactor (VEGF) and its receptors, flt-1 and KDR, in normal human emdometrium duringthe menstrual cycle.Methods: Immunohistochemical method was used to observe the expression ofVEGF and its two receptors in emdometrium throughout the normal menstrual cyclemeanwhile the isoforms of VEGF were also detected by Western blot analysis. The en-dothelial cells of micro-vessels were marked with Ⅷ factor antibody.Results: VEGF and its receptors existed in endometrial glandular, stromal and vas-cular endothelial cells of human endometrium. Their expressions were higher in the mid-secretory phase of menstrual cycle and highest at menstruation. VEGF121 and VEGF165were the predominant isoforms in normal human endometrium.Conclusion: The expression of VEGF and its two receptors showed cycle-dependentin human endometrium, probably involved in embryonic implantation and endometrialproliferation and differentiation.展开更多
Objective: To investigate the effect of indomethacin-Cu-IUD on the endometrium. Methods: Four kinds of IUDs were inserted into the uteri of rats and rabbits through laparotomy. The animals were killed at 1,3,6 months ...Objective: To investigate the effect of indomethacin-Cu-IUD on the endometrium. Methods: Four kinds of IUDs were inserted into the uteri of rats and rabbits through laparotomy. The animals were killed at 1,3,6 months after treatment and their uteri were taken for histological examination with either microscopy and transmission electron microscopy. The rats and rabbits without IUD served as control. Results: There was no obvious pathological change in indomethacin-Cu-IUD group at 1-6 months after insertion of IUD, similar to the control. There were some mild edema and hyperplasia of fibrous tissues in endometrium in Cu-IUD group. There was a significantly change in the vessels of microcirculation. Most vessels were normal or contracted in the indomethacin--Cu--IUD group (75 % ) and control group(87% ), while most vessels were dilated in the Cu-IUD group(70% ) (P<0. 01 ). Conclusion: Indomethacin--Cu-IUD has no harmful effect on endometrium.展开更多
Objective: To evaluate the relationships between Bcl-X expression and apoptosis in normal endometrium (NE), endometrial hyperplasia (EH) and adenocarcinoma (EA). Methods: Immunohistochemical technique was used to exam...Objective: To evaluate the relationships between Bcl-X expression and apoptosis in normal endometrium (NE), endometrial hyperplasia (EH) and adenocarcinoma (EA). Methods: Immunohistochemical technique was used to examine the localization and expression of Bcl-X proteins in 55 cases of NE, 18 cases of EH and 13 cases of EA. The expression form of Bcl-X protein in normal or abnormal endometrium was further characterized by Western blot analysis. Results: As assessed by immunohistochemistry, Bcl-X proteins were predominantly localized in cytoplasm and nuclear membrane of glandular epithelial cells of the basal layer during the proliferative phase, and the functional layer during the secretory phase. Level of Bcl-X protein was lower in proliferative phase and remarkably increased in the late secretory and the menstrual phase. By Western blotting, it was found the form of Bcl-X was mainly Bcl-XL in proliferative and secretory endometrium. Weak expression of Bcl-Xs was only found in secretory endometrium. Weak Bcl-X expression was also found in cytoplasm of glandular cells of nonatypical hyperplasia, but strong staining presented in atypical hyperplasia, and the only form detected by Western blotting was Bcl-XL. While in adenocarcinoma, both Bcl-XL. and Bcl-Xs existed but the amount of the long form was much higher than that of the short one. Conclusion: Our results suggest that the existance of Bcl-X, especially Bcl-XL plays a role in the regulation of apoptosis in the human endometrium, not only in cycling endometrium but also in endometrial hyperplasia and adenocarcinoma just like the other members of the Bcl-2 family.展开更多
Objective:To analyze mRNA and protein expression of osteopontin(OPN)in human endome-trium throughout menstrual cycle.Methods:Immunohistochemieal method was used to determine the level and the location ofOPN in normal ...Objective:To analyze mRNA and protein expression of osteopontin(OPN)in human endome-trium throughout menstrual cycle.Methods:Immunohistochemieal method was used to determine the level and the location ofOPN in normal cycling endometrium of 50 women.Western Blot analysis was also used to detectthe existence of OPN at proliferative and secretory phases in six samples.The levels of OPNmRNA in 18 samples were measured by RT-PCR.Results:The OPN mainly expressed in human endometrial glandular epithelium but not instromal cells.The expression was highest at mid and late secretory phases and menstruous phaseas well.No expression was found in early and mid proliferative endometria.Two subtypes ofOPN proteins(40 kDa-75 kDa)were detected by Western blot analysis in homogenized endome-tria at secretory phase.The level of OPN mRNA in secretory phase endometrium was significantlyhigher than that in proliferative phase.Conclusions:OPN was only found in endometrial glandular epithelial cells,and the OPN andits mRNA showed a pronounced cycle-dependent expression in human endometrium,higher ex-pression at mid and late secretory phases and menstruous phase.It's probably involved in embry-onic implantation and endometrial shedding.展开更多
Objective In order to gain further information about the mechanism of emergency contraception, during the peri-implantation period the effect of single and low dose of Mifepristone on the expression of integrin level ...Objective In order to gain further information about the mechanism of emergency contraception, during the peri-implantation period the effect of single and low dose of Mifepristone on the expression of integrin level in endometrium of healthy women were observed Materials ＆ Methods Eleven healthy women, proven fertility, were randomly divided into two groups: group LH-2 (n = 5) and LH+ 2 (n = 6). During the control and treatment cycle, placebo or 10 mg Mifepristone were given orally to group LH- 2 on cycle day LH- 2 or to group LH + 2 on cycle day LH - 2, respectively. One endometrial tissue specimen was obtained in both the control and the treatment cycle on cycle day LH+ 7.In this study, the endometrial specimens were assessed by immunohistochemistry analysis to measure the change of integrin α1, α4 and β3 subunits expression on the endometrium after using Mifepristone.Results Mifepristone increased the expression of α1 and α4 subunit in glandular epithelium only in group LH- 2. The expression of β3 integrin subunit remain the same in our experiments.Conclusion Treatment with Mifepristone interferes with integrin distribution during the implantation period, which may imply that the contraceptive effect of Mi fepristone is primarily due to impaired endometrial receptivity.展开更多
Objective To study the role of p16 and cyclin D 1 in the genesis and development of endometrial carcinoma.Methods 12 cases of normal endometrium,22 cases of proliferative endometrium and 41 cases of endometrial carcin...Objective To study the role of p16 and cyclin D 1 in the genesis and development of endometrial carcinoma.Methods 12 cases of normal endometrium,22 cases of proliferative endometrium and 41 cases of endometrial carcinoma were detected for the expression of p16 and cyclin D 1 by means of immunohistochemical S P. Results In normal endometrium p16 was expressed while cyclin D 1 was almost negative in the proliferative phase,but both of them were negative in the secretory phase.Among the groups of the simple and compound hyperplasia, the atypical hyperplasia and the endometrial carcinoma,the expression of p16 showed a descending tendency, while the expression of cyclin D 1 showed an ascending tendency.In endometrial carcinomas the expression of p16 was significantly lower than that of normal endometrium and proliferative endometrium( P <0.01, P <0.05).However, the expression of cyclin D 1 in proliferate endometrium and endometrial carcinoma was significantly higher than that in normal endometrium ( P<0.05,P<0.01) .The overexpression of cyclin D 1 in the atypical hyperplasia group was obviously different from that in the simple and compound hyperplasia group ( P <0.01).In endometrial carcinoma,the expression of p16 was decreasing with the descending of cell differentiate degree, on the opposite, the expression of cyclin D 1 was increased and there existed a negative correlation between them.It was also observed that the overexpression of cyclin D 1 was significant different between G 1 and G 2,G 3(P<0.01).Conclusion p16 is a negative regulating factor of cell cycle in endometrial carcinoma, while cyclin D 1 is a positive one.Both of them are important in the genesis and development of endometrial carcinoma.The low expression of p16 and the overexpression of cyclin D 1 are related with the malicious biological behaviors of endometrial carcinoma and maybe play an important role in the judgement of prognosis.Overexpression of cyclin D 1 may be an earlier molecular event in the genesis of endometrial carcinoma.展开更多
Introduction: Abnormal uterine bleeding, either due to organic or be dysfunctional cause, is a common gynaecological problems. Methods: A retrospective, cross sectional, hospital-based study was done for a period of f...Introduction: Abnormal uterine bleeding, either due to organic or be dysfunctional cause, is a common gynaecological problems. Methods: A retrospective, cross sectional, hospital-based study was done for a period of five and a half years included 1884 samples which were taken by endosampling as well as by curetting for the evaluation of several gynaecological symptoms. Results: The age distribution ranges from 16 to 83 years. 12.8% of (242/1884) samples were inadequate for a comprehensive diagnosis. The functional cause was the predominant in 1263 samples and organic causes were found in 379 sample. The menorrhagia is the commonest one and it is followed by post-menopausal bleeding and polymenorrhoea. Endometrial polyp was the predominant organic (46.9%) cause followed by (26.1%) simple endometrial hyperplasia without atypia. Most of the simple hyperplasia without atypia (49/99) and complex hyperplasia (10/28) also occurred in the same age group. Total 29 (1.5%) cases of carcinoma of endometrium were found and it was common (13/29) in 50 - 59 years of age. It was noted that (5/29) carcinoma occurred in less than 39 years of age. Conclusion: This study shows that most of the patients fall in the age group of 40 - 49 years. As the organic causes mostly found in this age group, endometrial cavity evaluation should be done more than 40 years of age. Further endometrial hyperplasia and carcinoma of the endometrium also occurs in less than 40 years of age. Therefore, clinical risk factors should be assessed and need of endometrial cavity should be individualised for better outcome.展开更多
The functional significance of the endometrial hCG/ LH receptors has been related to a rapid release of prostaglandins. However, as compared to gonads and myometrium, in-endometrium mechanisms of transmembrane signall...The functional significance of the endometrial hCG/ LH receptors has been related to a rapid release of prostaglandins. However, as compared to gonads and myometrium, in-endometrium mechanisms of transmembrane signalling of the hCG/LH receptors are probably not conventional and remain unclear. Here we investigated, in vivo, the potential of hCG to interact with, and stimulate the membrane effector enzyme, adenylyl cyclase (AC), in human endometrium. Hormonal and nonhormonal activation of AC was tested in membrane fractions prepared from endometrial biopsies obtained from patients undergoing evaluation cycles for hormone replacement therapy (HRT) and controlled ovarian hyperstimulation (COH). AC activity was determined by the direct conversion of the substrate ATP into cAMP under unstimulated conditions and in the presence of the non-hormonal activators guanyl nucleotide and forskolin. Also AC activity was tested in the presence of hCG under conditions allowing maximal enzyme stimulation. Isoproterenol and prostaglandin E2 (PGE2) were included for comparison. Immunoblot analyses demonstrated the presence of hCG/LH receptors and Gsα protein and other members of the G protein family in the membrane fractions. Endometrial membranes also exhibited high levels of AC activity compared to luteal membranes used as control. Stimulation by GMP-P(NH)P alone was 196 ± 63 (n = 8) (pmol/mg/ min ± SD). Neither hCG nor isoproterenol showed stimulation of endometrial AC (210 ± 65, and 197 ± 53, respectively;n = 66 assays). But PGE2 stimulated the enzyme system significantly (264 ± 63, p < 0.05;n = 66 assays). These data show that membrane fractions from human endometrium express all the AC system components, namely, hCG/LH receptors, Gsα protein and AC;however, hCG does not stimulate the endometrial AC system. Our data indicate that, in great contrast to gonadal receptors, endometrial hCG/ LH receptors are not coupled to the transmembrane AC effector. The well known release of eicosanoids in response to hCG suggests that these receptors are functional in human endometrium but throughout a signalling system different from AC. This enzyme is certainly coupled to and directly activated by eicosanoids and other embryonic signals.展开更多
The endometrial condition is a significant factor for successful pregnancy. To regulate endometrial function in fertility treatment, prednisolone (PSL) is administered for suppression of increased natural killer cells...The endometrial condition is a significant factor for successful pregnancy. To regulate endometrial function in fertility treatment, prednisolone (PSL) is administered for suppression of increased natural killer cells and stimulation of endometrium embryo transfer (SEET) to enhance communication between embryo and maternal tissues. We attempted to improve the endometrial condition by PSL administration and SEET during frozen–thawed blastocyst transfer (FBT). Patients took PSL (5 mg) 3 times daily for 3 days after ovulation during the FBT cycle. To analyse effects of PSL combined with SEET, we determined rates of chemical pregnancy, clinical pregnancy, foetal heart movement (FHM) and live birth. Rates of chemical pregnancy, clinical pregnancy and FHM were significantly higher in the PSL(+)/SEET(+) (57.7%, 50.0% and 46.2%, respectively) and PSL(+)/SEET(-) (53.3%, 46.7% and 46.7%, respectively) groups than in the PSL(-)/SEET(+) (30.3%, 18.2% and 18.2%, respectively) and PSL(-)/SEET(-) (22.4%, 22.4% and 18.4%;P = 0.0043, 0.0081 and 0.0055, respectively) groups. The live birth rate was significantly higher in the PSL(+)/SEET(+) group than in the PSL(+)/SEET(-), PSL(-)/SEET(+) and PSL(-)/SEET(-) groups (42.3%, 26.7%, 18.2% and 12.2%, respectively;P = 0.0237). PSL combined with SEET may be a useful adjunct to assisted reproductive technology in women who repeatedly fail to conceive by infertility treatment.展开更多
Objective: The presence of nerve fibers in human endometrium remains unsettled but recent immunocytochemical studies have shown that there was increased innervation in the endometrium from women with endometriosis and...Objective: The presence of nerve fibers in human endometrium remains unsettled but recent immunocytochemical studies have shown that there was increased innervation in the endometrium from women with endometriosis and some nerve fibers in the normally cycling human endometrium. In the current study, we used uterine tissue cryosections from normal cycling women, which previously provided better immunocytochemical staining for lymphatic vessels than in paraffin sections. Materials and Methods: A total of 16 cases from normally cycling women were included representing menstrual, early proliferative, early to late secretary phase. Neurofilament and CD 56 were used as immunocytochemical markers for nerve fibers with cryosections. Results: There were consistent presence of nerve fibers in myometrium and basalis. Few small nerve fibers were identified in early proliferative endometrium and more nerve fibers were present in lower-half functionalis from mid-secretary phase. Late-secretary functionalis showed less nerve fibers in the upper-half than the lower-half functionalis, implying growing nerve fibers from lower functionalis to upper functionalis in late-secretary phase. Conclusion: Nerve fibers appeared to cyclically grow from basalis to lower functionalis and then from lower functionalis to upper functionalis concomitantly with blood vessels in normally cycling human endometrium. These cycling endometrial nerve fibers consisted mostly of nonmyelinated small nerve fibers, which may transmit pelvic pain in the normally cycling women.展开更多
文摘BACKGROUND Large-cell neuroendocrine carcinoma(NEC)is an uncommon type of tumor that can occur in the endometrium.This aggressive cancer requires definitive management.Here,we describe the clinical characteristics and treatment of a postmenopausal woman with large cell NEC of the endometrium.CASE SUMMARY A 55-year-old Asian female presented with a 1-year history of postmenopausal vaginal bleeding.Transvaginal ultrasound revealed a thickened endometrium(30.2 mm)and a hypervascular tumor.Computed tomography revealed that the tumor had invaded more than half of the myometrium and spread to the pelvic lymph nodes.The tumor marker,carcinoembryonic antigen,was elevated(3.65 ng/mL).Endocervical biopsy revealed high-grade endometrial carcinoma.She underwent radical hysterectomy,bilateral salpingo-oophorectomy,omentectomy,and bilateral pelvic and para-aortic lymph node dissection.Pathological examination revealed mixed neuroendocrine and endometrioid adenocarcinoma,pT2N0M0,grade 3,and International Federation of Gynecology and Obstetrics stage 2.Immunohistochemistry showed moderate estrogen and progesterone receptor expressions(20%and 1%,respectively),focal CD56 expression(NEC marker),positive staining for vimentin,p53(wild type),and ki67(90%),and loss of expression of PMS2(Lynch syndrome marker).The patient received five cycles of cisplatin and etoposide after surgery.No recurrence was noted after 5 mo.CONCLUSION We report the characteristics and successful management of a rare case of large cell endometrial NEC concomitant with Lynch syndrome.
基金supported by PhD research startup foundation of Northwest A&F University(00400/Z109021811)National Key Research and Development Program of China(2016YFD0500508)Shaanxi Science and Technology Innovation Project Plan(2015KTCQ03–08)
文摘Background: Recent studies have revealed that noncoding RNAs play important regulatory roles in the formation of endometrial receptivity.Circular RNAs(circRNAs) are a universally expressed noncoding RNA species that have been recently proposed to act as miRNA sponges that directly regulate expression of target genes or parental genes.Results: We used Illumina Solexa technology to analyze the expression profiles of circRNAs in the endometrium from three goats at gestational day 5(pre-receptive endometrium,PE) and three goats at gestational day 15(receptive endometrium,RE).Overall,21,813 circRNAs were identified,of which 5,925 circRNAs were specific to the RE and 9,078 were specific to the PE,which suggested high stage-specificity.Further analysis found 334 differentially expressed circRNAs in the RE compared with PE(P < 0.05).The analysis of the circRNA-miRNA interaction network further supported the idea that circRNAs act as miRNA sponges to regulate gene expression.Moreover,some circRNAs were regulated by estrogen(E2)/progesterone(P4) in endometrial epithelium cell lines(EECs) and endometrial stromal cell line(ESCs),and each circRNA molecule exhibited unique regulation characteristics with respect to E2 and P4.Conclusions: These data provide an endometrium circRNA expression atlas corresponding to the biology of the goat receptive endometrium during embryo implantation.
基金the China Postdoctoral Science Foundation(2019M653776,2020M673516)the National Key Research and Development Program of China(2016YFD0500508)+1 种基金the Natural Science Foundation of Shaanxi Province,China(2020JQ-265)the PhD research startup foundation of Northwest A&F University,China(00400/Z109021811)。
文摘Endometrial development is a complicated process involving numerous regulatory factors.Circular RNAs(circRNAs)have been known as a member of the naturally occurring non-coding RNA family,and are reportedly crucial for a variety of physiological processes.This study investigated the circRNA landscape of non-pregnant endometrium of dairy goats during estrus.Non-pregnant endometrial samples of goats at estrus day 5(Ed5)and estrus day 15(Ed15)were used to methodically analyze the circRNA landscape using strand-specific Ribo-Zero RNA-Seq.A total of 2331 differentially expressed(P<0.05)circRNAs(DEciRs)between Ed5 and Ed15 were discovered in the goat endometrium.It was found that Nipped-B-like(NIPBL)and calcium responsive transcription factor(CARF)may participate in the development of the endometrium by decreasing(P<0.05)the levels of their circRNA-transcript forms.Furthermore,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses of DEciR host genes(hgDEciRs)revealed that tight junctions and GTPases may be involved in endometrial development during the estrus cycle.A total of 2331 DEciRs were discovered in the endometrium at Ed5 and Ed15.Based on GO and KEGG enrichment analyses,it could be inferred that tight junctions and GTPases are likely to play an important role in the development of goat endometrium during the estrus cycle.This circRNA study greatly enhances our knowledge of global trends in the development of non-pregnant endometrium during the estrus cycle in goats;these results help us to better understand the molecular regulation of endometrial development in dairy goats.
基金This project was supported by a grantfrom Hubei Scienceand Technology Comm ittee (No.96 1P190 1)
文摘The activity of matrix metalloproteinases (MMPs) in the uterine flushing and endometrial tissue of normal adult women wearing FCu IUD (fixed Cu IUD) or FICu IUD (indomethacin releasing FCu IUD) was observed by using zymography on SDS PAGE containing gelatin. The results showed that the activity and kinds of MMPs in FCu IUD group were increased significantly as compared with themselves before being inserted FCu IUD. However, compared with the FCu IUD group, the activity of some kinds of MMPs in the FICu IUD group was decreased significantly. These data suggest that IUD can enhance the activity of MMPs in human endometrium, intermediated by prostaglandins, and MMPs may have relation to IUD induced menorrhagia and indomethacin reduces IUD induced menorrhagia by partly inhibiting MMPs synthesis.
基金The financial support was prepared by the Research Council of Kermanshah University of Medical Sciences for PhD thesis(Research project No.4000077).
文摘Background:Endometriosis can lead to infertility.Since there is no definitive treat-ment for endometriosis,animal modelling seems necessary to examine the possible treatments.Mouse endometrium cannot be separated for endometriosis induc-tion.In addition,transplantation of uterus into the abdominal viscera to induce endometriosis causes organ damage.In this study,we defined a new model of en-dometriosis leading to separability of endometrium and a safe anatomical region for transplantation.Methods:Forty female mice were allocated to 5 groups:1,sham;2,allograft uterus transplantation of mice to anterior abdominal wall of mice;3,allograft uterus trans-plantation of mice to mesentery of mice;4,xenograft endometrial transplantation of rat to anterior abdominal wall of mice;5,xenograft endometrial transplantation of rat to mesentery of mice.Adult female rats with a previous pregnancy experience were selected and placed in the vicinity of male rats for 2 weeks to induce estrogen secre-tion and increase endometrial thickness.Results:In the 4th group of animals,compared to sham,the peritoneal concentrations of VEGF-A,TNF-α,NO,MDA,and serum levels of CA-125 and IL-37 were increased and total body weight was decreased,while weight and size of endometrial lesions were increased significantly(P<.05).Genes expression of HOXA10 and HOXA11 were decreased significantly(P<.05)in groups 2 and 4 compared to sham.Conclusions:Xenograft transplantation of endometrium from rat to anterior abdomi-nal wall of mice can potentially mimic human endometriosis morphologically,histo-logically,and genetically.
文摘Objective:The aim of this study was to determine the expression of Hoxa 10 in endometrium during the menstrual cycle and their response to sex steroids and HB-EGF.Methods:Forty endometrial samples from regularly cycling women were studied.The endometrial epithelial(EEC)and stromal(ESC)cells isolated by collagenase Ⅰ digestion and mechanical dissociation was cultured from every sample.The endometrial stromal cells(ESC)were incubated with 17-beta estradiol(10-8mol/L),medroxyprogesterone acetate(MPA)(10-6mol/L),RU486(10-8mol/L)or HB-EGF(10ng/ml)for 48 hours respectively.The expression of Hoxa10 mRNA was demonstrated by reverse transcription-polymerase chain reaction(RT-PCR).Result:Hoxa10 showed a regulated cycle phase-dependent expression pattern in stromal cells and epithelial cells.Hoxa10 expression dramatically increased during the midsecretory phase of the menstrual cycle,at the time of implantation.The expression of Hoxa10 in cultured endometrial stromal cells was stimulated by estrogen,progesterone and HB-EGF.Conclusion:The cycle phase-specific expression of Hoxa10 and up-regulated by sex steroids and HB-EGF suggests a tight regulation and establishing conditions necessary for implantation.
基金Supported by Key Research and Development Project in Department of Science and Technology,Liaoning Province,No.2017225025
文摘BACKGROUND Postmenopausal bleeding and an endometrial thickness≥5 mm on sonograms of menopausal women can indicate the presence of endometrial lesions.Diagnostic hysteroscopy is a powerful method for endometrial diseases.AIM To investigate the pathological pattern of endometrial abnormalities in postmenopausal women with bleeding or asymptomatic thickened endometrium diagnosed by hysteroscopy.METHODS A total of 187 postmenopausal women with bleeding or asymptomatic thickened endometrium underwent diagnostic hysteroscopy.The women were subsequently divided into three groups:Postmenopausal bleeding(PMB)group(n=84),asymptomatic group(n=94),and additional group(n=9).Women in the additional group manifested abdominal pain and leukorrhagia.RESULTS Among the 187 patients examined,84(44.9%)were diagnosed with PMB and 94(50.3%)with asymptomatic thickened endometrium.Endometrial polyp was the most common endometrial abnormality,which was detected in 51.2%,76.6%and 77.8%of the PMB,asymptomatic,and additional groups,respectively.In the PMB group,7(8.3%)women had hyperplasia with atypia and 14(16.7%)had endometrial adenocarcinoma.Fewer malignant lesions were detected in the asymptomatic group.Endometrial hyperplasia without atypia was found in 8.3%of the PMB group and 7.4%of the asymptomatic group.CONCLUSION Endometrial polyp was the most common pathology in the PMB group.Diagnostic hysteroscopy is recommended for women with PMB and asymptomatic thickened endometrium.
文摘Pathogenesis of the endometriosis is complex and the etiology is still unclear. The objective of this study was to examine that endometrial gene expression in late secretory phase endometrium differs between patients with and without endometriosis. Five patients with proven advanced-stage endometriosis and 5 controls underwent endometrial biopsy in the late secretory phase. Analysis of eutopic endometrial gene expression was performed using Affymetrix gene arrays and differentially expressed genes were assigned to gene ontology groups based on overrepresented analysis using Database for Annotation, Visualization, and Integrated Discovery software. Four hundred sixty two genes were identified as up-regulated such as matrix metalloproteinase 10, cytochrome P450 family 24 subfamily A polypeptide 1, matrix metalloproteinase 3, chemokine (C-C motif) ligand 20, Rho family GTPase 1, interleukin 1-beta, and insulin-like growth factor binding protein 1. Six hundred forty three genes were down-regulated in all endometriotic samples. A lot of genes related with metabolic process, cellular ketone metabolic process and ncRNA metabolic processing were included. Expression patterns of selected five genes were validated by quantitative real time PCR. The results of this analysis support that the eutopic endometrium from patients with advanced-stage endometriosis has distinct gene expression profile from eutopic endometrium of control without endometriosis.
文摘The role of the tumor necrosis factor (TNF) system in endometriosis is not completely clear and therefore was the focus of this study. In eutopic endometria obtained from women with (n = 41) and without (controls;n = 34) endometriosis during laparoscopy, the subcellular location and the percentages for TNF, TNFR1, TNFR2 and CD45 positive-cells were determined (immunohistochemistry);the protein concentration (ELISA) of the soluble receptors (sTNFR1 and sTNFR2) were measured in 4h-explants culture media and the TNF concentration was performed in ex vivo endometrial homogenates. The TNF, TNFR1 and TNFR2 mRNAs were analyzed by real-time PCR. In control endometria, TNF, TNFR1 and sTNFR1 proteins increased during the late secretory phase. In endometriosis endometria, the protein highest level of TNFR1 was reached during the early and the mid secretory phases and of sTNFR1 concentration during the proliferative phase;however, during the late secretory phase, both TNFR1 and sTNFR1 protein levels were reduced compared to the control endometria (p sTNFR2 concentrations, and TNF and TNFR2 mRNAs were similar in control and endometriosis endometria. Although TNFR1 mRNA was highly expressed, no significant differences were found between control and endometriosis endometria. In summary, this study establishes that TNF and TNFR1 protein expressions and the sTNFR concentrations in eutopic endometria from women with and without endometriosis are dependent on the menstrual cycle. The differences on the TNFR1 and sTNFR1 protein pattern between both groups, mainly during the mid and late secretory phases may play a role in the lower implantation rates observed in women with endometriosis, and also could be related to the altered cell death, which favor the augmented cell viability facilitating the characteristic endometrial implantation and growth outside the uterus in this disease.
文摘Objectives: We try to demonstrate the expression of vascular endothelial growthfactor (VEGF) and its receptors, flt-1 and KDR, in normal human emdometrium duringthe menstrual cycle.Methods: Immunohistochemical method was used to observe the expression ofVEGF and its two receptors in emdometrium throughout the normal menstrual cyclemeanwhile the isoforms of VEGF were also detected by Western blot analysis. The en-dothelial cells of micro-vessels were marked with Ⅷ factor antibody.Results: VEGF and its receptors existed in endometrial glandular, stromal and vas-cular endothelial cells of human endometrium. Their expressions were higher in the mid-secretory phase of menstrual cycle and highest at menstruation. VEGF121 and VEGF165were the predominant isoforms in normal human endometrium.Conclusion: The expression of VEGF and its two receptors showed cycle-dependentin human endometrium, probably involved in embryonic implantation and endometrialproliferation and differentiation.
文摘Objective: To investigate the effect of indomethacin-Cu-IUD on the endometrium. Methods: Four kinds of IUDs were inserted into the uteri of rats and rabbits through laparotomy. The animals were killed at 1,3,6 months after treatment and their uteri were taken for histological examination with either microscopy and transmission electron microscopy. The rats and rabbits without IUD served as control. Results: There was no obvious pathological change in indomethacin-Cu-IUD group at 1-6 months after insertion of IUD, similar to the control. There were some mild edema and hyperplasia of fibrous tissues in endometrium in Cu-IUD group. There was a significantly change in the vessels of microcirculation. Most vessels were normal or contracted in the indomethacin--Cu--IUD group (75 % ) and control group(87% ), while most vessels were dilated in the Cu-IUD group(70% ) (P<0. 01 ). Conclusion: Indomethacin--Cu-IUD has no harmful effect on endometrium.
文摘Objective: To evaluate the relationships between Bcl-X expression and apoptosis in normal endometrium (NE), endometrial hyperplasia (EH) and adenocarcinoma (EA). Methods: Immunohistochemical technique was used to examine the localization and expression of Bcl-X proteins in 55 cases of NE, 18 cases of EH and 13 cases of EA. The expression form of Bcl-X protein in normal or abnormal endometrium was further characterized by Western blot analysis. Results: As assessed by immunohistochemistry, Bcl-X proteins were predominantly localized in cytoplasm and nuclear membrane of glandular epithelial cells of the basal layer during the proliferative phase, and the functional layer during the secretory phase. Level of Bcl-X protein was lower in proliferative phase and remarkably increased in the late secretory and the menstrual phase. By Western blotting, it was found the form of Bcl-X was mainly Bcl-XL in proliferative and secretory endometrium. Weak expression of Bcl-Xs was only found in secretory endometrium. Weak Bcl-X expression was also found in cytoplasm of glandular cells of nonatypical hyperplasia, but strong staining presented in atypical hyperplasia, and the only form detected by Western blotting was Bcl-XL. While in adenocarcinoma, both Bcl-XL. and Bcl-Xs existed but the amount of the long form was much higher than that of the short one. Conclusion: Our results suggest that the existance of Bcl-X, especially Bcl-XL plays a role in the regulation of apoptosis in the human endometrium, not only in cycling endometrium but also in endometrial hyperplasia and adenocarcinoma just like the other members of the Bcl-2 family.
文摘Objective:To analyze mRNA and protein expression of osteopontin(OPN)in human endome-trium throughout menstrual cycle.Methods:Immunohistochemieal method was used to determine the level and the location ofOPN in normal cycling endometrium of 50 women.Western Blot analysis was also used to detectthe existence of OPN at proliferative and secretory phases in six samples.The levels of OPNmRNA in 18 samples were measured by RT-PCR.Results:The OPN mainly expressed in human endometrial glandular epithelium but not instromal cells.The expression was highest at mid and late secretory phases and menstruous phaseas well.No expression was found in early and mid proliferative endometria.Two subtypes ofOPN proteins(40 kDa-75 kDa)were detected by Western blot analysis in homogenized endome-tria at secretory phase.The level of OPN mRNA in secretory phase endometrium was significantlyhigher than that in proliferative phase.Conclusions:OPN was only found in endometrial glandular epithelial cells,and the OPN andits mRNA showed a pronounced cycle-dependent expression in human endometrium,higher ex-pression at mid and late secretory phases and menstruous phase.It's probably involved in embry-onic implantation and endometrial shedding.
文摘Objective In order to gain further information about the mechanism of emergency contraception, during the peri-implantation period the effect of single and low dose of Mifepristone on the expression of integrin level in endometrium of healthy women were observed Materials ＆ Methods Eleven healthy women, proven fertility, were randomly divided into two groups: group LH-2 (n = 5) and LH+ 2 (n = 6). During the control and treatment cycle, placebo or 10 mg Mifepristone were given orally to group LH- 2 on cycle day LH- 2 or to group LH + 2 on cycle day LH - 2, respectively. One endometrial tissue specimen was obtained in both the control and the treatment cycle on cycle day LH+ 7.In this study, the endometrial specimens were assessed by immunohistochemistry analysis to measure the change of integrin α1, α4 and β3 subunits expression on the endometrium after using Mifepristone.Results Mifepristone increased the expression of α1 and α4 subunit in glandular epithelium only in group LH- 2. The expression of β3 integrin subunit remain the same in our experiments.Conclusion Treatment with Mifepristone interferes with integrin distribution during the implantation period, which may imply that the contraceptive effect of Mi fepristone is primarily due to impaired endometrial receptivity.
文摘Objective To study the role of p16 and cyclin D 1 in the genesis and development of endometrial carcinoma.Methods 12 cases of normal endometrium,22 cases of proliferative endometrium and 41 cases of endometrial carcinoma were detected for the expression of p16 and cyclin D 1 by means of immunohistochemical S P. Results In normal endometrium p16 was expressed while cyclin D 1 was almost negative in the proliferative phase,but both of them were negative in the secretory phase.Among the groups of the simple and compound hyperplasia, the atypical hyperplasia and the endometrial carcinoma,the expression of p16 showed a descending tendency, while the expression of cyclin D 1 showed an ascending tendency.In endometrial carcinomas the expression of p16 was significantly lower than that of normal endometrium and proliferative endometrium( P <0.01, P <0.05).However, the expression of cyclin D 1 in proliferate endometrium and endometrial carcinoma was significantly higher than that in normal endometrium ( P<0.05,P<0.01) .The overexpression of cyclin D 1 in the atypical hyperplasia group was obviously different from that in the simple and compound hyperplasia group ( P <0.01).In endometrial carcinoma,the expression of p16 was decreasing with the descending of cell differentiate degree, on the opposite, the expression of cyclin D 1 was increased and there existed a negative correlation between them.It was also observed that the overexpression of cyclin D 1 was significant different between G 1 and G 2,G 3(P<0.01).Conclusion p16 is a negative regulating factor of cell cycle in endometrial carcinoma, while cyclin D 1 is a positive one.Both of them are important in the genesis and development of endometrial carcinoma.The low expression of p16 and the overexpression of cyclin D 1 are related with the malicious biological behaviors of endometrial carcinoma and maybe play an important role in the judgement of prognosis.Overexpression of cyclin D 1 may be an earlier molecular event in the genesis of endometrial carcinoma.
文摘Introduction: Abnormal uterine bleeding, either due to organic or be dysfunctional cause, is a common gynaecological problems. Methods: A retrospective, cross sectional, hospital-based study was done for a period of five and a half years included 1884 samples which were taken by endosampling as well as by curetting for the evaluation of several gynaecological symptoms. Results: The age distribution ranges from 16 to 83 years. 12.8% of (242/1884) samples were inadequate for a comprehensive diagnosis. The functional cause was the predominant in 1263 samples and organic causes were found in 379 sample. The menorrhagia is the commonest one and it is followed by post-menopausal bleeding and polymenorrhoea. Endometrial polyp was the predominant organic (46.9%) cause followed by (26.1%) simple endometrial hyperplasia without atypia. Most of the simple hyperplasia without atypia (49/99) and complex hyperplasia (10/28) also occurred in the same age group. Total 29 (1.5%) cases of carcinoma of endometrium were found and it was common (13/29) in 50 - 59 years of age. It was noted that (5/29) carcinoma occurred in less than 39 years of age. Conclusion: This study shows that most of the patients fall in the age group of 40 - 49 years. As the organic causes mostly found in this age group, endometrial cavity evaluation should be done more than 40 years of age. Further endometrial hyperplasia and carcinoma of the endometrium also occurs in less than 40 years of age. Therefore, clinical risk factors should be assessed and need of endometrial cavity should be individualised for better outcome.
文摘The functional significance of the endometrial hCG/ LH receptors has been related to a rapid release of prostaglandins. However, as compared to gonads and myometrium, in-endometrium mechanisms of transmembrane signalling of the hCG/LH receptors are probably not conventional and remain unclear. Here we investigated, in vivo, the potential of hCG to interact with, and stimulate the membrane effector enzyme, adenylyl cyclase (AC), in human endometrium. Hormonal and nonhormonal activation of AC was tested in membrane fractions prepared from endometrial biopsies obtained from patients undergoing evaluation cycles for hormone replacement therapy (HRT) and controlled ovarian hyperstimulation (COH). AC activity was determined by the direct conversion of the substrate ATP into cAMP under unstimulated conditions and in the presence of the non-hormonal activators guanyl nucleotide and forskolin. Also AC activity was tested in the presence of hCG under conditions allowing maximal enzyme stimulation. Isoproterenol and prostaglandin E2 (PGE2) were included for comparison. Immunoblot analyses demonstrated the presence of hCG/LH receptors and Gsα protein and other members of the G protein family in the membrane fractions. Endometrial membranes also exhibited high levels of AC activity compared to luteal membranes used as control. Stimulation by GMP-P(NH)P alone was 196 ± 63 (n = 8) (pmol/mg/ min ± SD). Neither hCG nor isoproterenol showed stimulation of endometrial AC (210 ± 65, and 197 ± 53, respectively;n = 66 assays). But PGE2 stimulated the enzyme system significantly (264 ± 63, p < 0.05;n = 66 assays). These data show that membrane fractions from human endometrium express all the AC system components, namely, hCG/LH receptors, Gsα protein and AC;however, hCG does not stimulate the endometrial AC system. Our data indicate that, in great contrast to gonadal receptors, endometrial hCG/ LH receptors are not coupled to the transmembrane AC effector. The well known release of eicosanoids in response to hCG suggests that these receptors are functional in human endometrium but throughout a signalling system different from AC. This enzyme is certainly coupled to and directly activated by eicosanoids and other embryonic signals.
文摘The endometrial condition is a significant factor for successful pregnancy. To regulate endometrial function in fertility treatment, prednisolone (PSL) is administered for suppression of increased natural killer cells and stimulation of endometrium embryo transfer (SEET) to enhance communication between embryo and maternal tissues. We attempted to improve the endometrial condition by PSL administration and SEET during frozen–thawed blastocyst transfer (FBT). Patients took PSL (5 mg) 3 times daily for 3 days after ovulation during the FBT cycle. To analyse effects of PSL combined with SEET, we determined rates of chemical pregnancy, clinical pregnancy, foetal heart movement (FHM) and live birth. Rates of chemical pregnancy, clinical pregnancy and FHM were significantly higher in the PSL(+)/SEET(+) (57.7%, 50.0% and 46.2%, respectively) and PSL(+)/SEET(-) (53.3%, 46.7% and 46.7%, respectively) groups than in the PSL(-)/SEET(+) (30.3%, 18.2% and 18.2%, respectively) and PSL(-)/SEET(-) (22.4%, 22.4% and 18.4%;P = 0.0043, 0.0081 and 0.0055, respectively) groups. The live birth rate was significantly higher in the PSL(+)/SEET(+) group than in the PSL(+)/SEET(-), PSL(-)/SEET(+) and PSL(-)/SEET(-) groups (42.3%, 26.7%, 18.2% and 12.2%, respectively;P = 0.0237). PSL combined with SEET may be a useful adjunct to assisted reproductive technology in women who repeatedly fail to conceive by infertility treatment.
文摘Objective: The presence of nerve fibers in human endometrium remains unsettled but recent immunocytochemical studies have shown that there was increased innervation in the endometrium from women with endometriosis and some nerve fibers in the normally cycling human endometrium. In the current study, we used uterine tissue cryosections from normal cycling women, which previously provided better immunocytochemical staining for lymphatic vessels than in paraffin sections. Materials and Methods: A total of 16 cases from normally cycling women were included representing menstrual, early proliferative, early to late secretary phase. Neurofilament and CD 56 were used as immunocytochemical markers for nerve fibers with cryosections. Results: There were consistent presence of nerve fibers in myometrium and basalis. Few small nerve fibers were identified in early proliferative endometrium and more nerve fibers were present in lower-half functionalis from mid-secretary phase. Late-secretary functionalis showed less nerve fibers in the upper-half than the lower-half functionalis, implying growing nerve fibers from lower functionalis to upper functionalis in late-secretary phase. Conclusion: Nerve fibers appeared to cyclically grow from basalis to lower functionalis and then from lower functionalis to upper functionalis concomitantly with blood vessels in normally cycling human endometrium. These cycling endometrial nerve fibers consisted mostly of nonmyelinated small nerve fibers, which may transmit pelvic pain in the normally cycling women.
