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1.
Yonsei Med J ; 61(4): 317-322, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32233174

RESUMO

PURPOSE: To evaluate factors associated with endometrial pathology during tamoxifen use in premenopausal breast cancer (BC) patients. MATERIALS AND METHODS: We reviewed the medical records of premenopausal BC patients treated with tamoxifen who underwent endometrial biopsy with or without hysteroscopy. Clinical characteristics were compared between women with endometrial pathology (endometrial hyperplasia or cancer) and those with normal histology or endometrial polyps. RESULTS: Among 284 endometrial biopsies, endometrial hyperplasia was diagnosed in 7 patients (2.5%), endometrial cancer was diagnosed in 5 patients (1.8%), normal histology was noted in 146 patients (51.4%), and endometrial polyp was present in 114 patients (40.1%). When comparing women with endometrial cancer (n=5) to women with normal histology, abnormal uterine bleeding was more common (p=0.007), and endometrial thickness was greater (p=0.007) in women with endometrial cancer. Chemotherapy for BC was also more common in patients with endometrial cancer (p=0.037). When comparing women with endometrial polyps and those with endometrial hyperplasia or cancer, the presence of abnormal uterine bleeding was more common in patients with endometrial hyperplasia or cancer (p<0.001); however, tamoxifen duration and endometrial thickness did not differ significantly between the two groups. CONCLUSION: In premenopausal BC patients treated with tamoxifen, abnormal uterine bleeding, increased endometrial thickness, and chemotherapy for BC were associated with the occurrence of endometrial cancer. These findings may provide useful information for gynecologic surveillance and counseling during tamoxifen treatment in premenopausal BC patients.


Assuntos
Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Hiperplasia Endometrial/induzido quimicamente , Neoplasias do Endométrio/induzido quimicamente , Endométrio/efeitos dos fármacos , Pólipos/induzido quimicamente , Pré-Menopausa , Tamoxifeno/efeitos adversos , Adulto , Antineoplásicos Hormonais/uso terapêutico , Biópsia , Hiperplasia Endometrial/diagnóstico por imagem , Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/diagnóstico por imagem , Neoplasias do Endométrio/patologia , Endométrio/diagnóstico por imagem , Endométrio/patologia , Feminino , Humanos , Histeroscopia , Pessoa de Meia-Idade , Pólipos/diagnóstico por imagem , Pólipos/patologia , Fatores de Risco , Tamoxifeno/uso terapêutico , Fatores de Tempo , Doenças Uterinas , Neoplasias Uterinas/induzido quimicamente , Neoplasias Uterinas/patologia
2.
Expert Rev Clin Pharmacol ; 13(2): 163-182, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31975619

RESUMO

Introduction: Steroid hormones are responsible for specific changes in the endometrium during the menstrual cycle, when they are sequentially secreted and, because of this, in the early days sequential combined oral contraceptive regimens were utilized. The same basic concept has been utilized with multi-phasic regimens, in order to produce endometrial pictures mimicking the normal cycle.Areas covered: The Endometrial effects of progestins and estrogens; combined monophasic high- (50 µg), medium- (30 µg), low- (20 µg), ultralow- (15 µg) estrogen content; sequential regimens; multiphasic combinations; treatment schedules.Cervical effects of combined high-dose and sequential combinations, including evidence for an increase in malignant lesions.Expert opinion: Overall, combined oral contraceptives (COCs) inhibit normal proliferative changes and the endometrium becomes thin, narrow, with widely spaced glands and pre-decidual changes in the stroma. During the first few cycles the progestin induces a coexistence of proliferative and secretory features; with time, the picture changes because the progestin induces a down-regulation of estrogen receptors, resulting in tortuous glands similar to those in the secretory phase, but characterized by a quiescent, atrophic glandular epithelium.In the cervical epithelium, under the influence of high-dose COCs, endocervical glands became hypersecretory and in some instances, distinctive type of atypical polypoid endocervical hyperplasia is found.


Assuntos
Anticoncepcionais Orais Combinados/administração & dosagem , Estrogênios/administração & dosagem , Progestinas/administração & dosagem , Animais , Colo do Útero/efeitos dos fármacos , Colo do Útero/metabolismo , Anticoncepcionais Orais Combinados/efeitos adversos , Anticoncepcionais Orais Combinados/farmacologia , Relação Dose-Resposta a Droga , Endométrio/efeitos dos fármacos , Endométrio/metabolismo , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Estrogênios/efeitos adversos , Estrogênios/farmacologia , Feminino , Humanos , Progestinas/efeitos adversos , Progestinas/farmacologia
3.
Medicine (Baltimore) ; 99(4): e18383, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31977842

RESUMO

OBJECTIVE: To compare the effects of letrozole and human menopausal gonadotropin (HMG) in the treatment of patients with polycystic ovary syndrome (PCOS) resistant to clomiphene citrate (CC). METHODS: A total of 96 clomiphene resistance polycystic ovary syndrome patients infertility were randomly divided into an LE group, and HMG group (n = 48). LE group orally received letrozole at 5.0 mg/d on the 3rd-5th days of menstrual cycle for 5 consecutive days, and 75 U/d HMG was given through intramuscular injection for 5 days starting from the third day of menstrual cycle in HMG group. Number of growing and mature follicles, serum E2 (pg/mL), serum P (ng/mL), endometrial thickness, occurrence of pregnancy and miscarriage were observed. RESULTS: There was no significant difference in the number of ovulation cycles between the 2 groups (53.6% vs 64.7%, P > .05). The number of mature follicular cycles in the HMG group was higher than that of the letrozole group (P < .01). There were no significant differences in the clinical pregnancy rate (22.9% vs 27.1%, P > .05) and abortion rate (6.2% vs 10.4%, P > .05). There was no significant difference in the endometrial thickness between the 2 groups on the day of HCG injection [(9.1 ±â€Š0.2) mm vs (10.7 ±â€Š1.6) mm, P > .05]; the serum estradiol (E2) was lower in the letrozole group. The incidence of ovarian cysts was lower than that of HMG group (P < .05). There was2 ovarian hyperstimulation syndrome in the letrozole group; the incidence of ovarian hyperstimulation syndrome in the HMG group was 12.5%. CONCLUSION: Letrozole-induced ovulation can obtain ovulation rate and pregnancy rate similar to gonadotropin, but reduce the risk associated with treatment. It can be used as an effective ovulation option for patients with polycystic ovary syndrome who are resistant to clomiphene.


Assuntos
Infertilidade Feminina/tratamento farmacológico , Letrozol/uso terapêutico , Menotropinas/uso terapêutico , Indução da Ovulação/métodos , Síndrome do Ovário Policístico/tratamento farmacológico , Aborto Espontâneo/epidemiologia , Adulto , Clomifeno/farmacologia , Endométrio/efeitos dos fármacos , Estradiol/sangue , Feminino , Humanos , Cistos Ovarianos/induzido quimicamente , Síndrome de Hiperestimulação Ovariana/induzido quimicamente , Ovulação/efeitos dos fármacos , Gravidez , Adulto Jovem
4.
Toxicol Lett ; 319: 242-249, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31733320

RESUMO

Humans are typically exposed to mixtures of substances, whereby their bioactivity can be significantly altered by co-occurring compounds. Thus, over the last years, research on combinatory effects has gained increasing attention. In particular, several xenoestrogens have been recently reported to interact synergistically, among them alternariol (AOH) and zearalenone (ZEN), two toxins produced by molds which contaminate crops or food commodities. Bisphenol A (BPA) is a potential food contaminant arising from its use in plastics and represents a well-known xenoestrogen, acting as an endocrine disruptor. However, little research was yet conducted on its impact on the bioactivity of other xenoestrogens, and vice versa. Thus, in this study, we focused on combinatory estrogenic effects of BPA with AOH and ZEN in Ishikawa cells, which represent a well-established, estrogen-sensitive human cell model. Estrogenic stimuli of the single compounds and binary combinations in constant concentration ratios were measured by assessing the activity of alkaline phosphatase, a natural reporter gene for estrogen receptor activation. In parallel, cytotoxicity was monitored by neutral red assay. For statistical analysis of combinatory effects the "combination index" model was applied. In combination with ZEN, BPA was found to cause additive estrogenic effects. Mixtures of BPA with AOH expressed moderately antagonistic to nearly additive combinatory effects, depending on the concentration ratio. Although no synergistic effects were measured in the applied chemical mixtures, additive estrogenic stimuli were observed, underlining the importance to consider the cumulative impact of endocrine active factors out of different sources and structural classes.


Assuntos
Compostos Benzidrílicos/toxicidade , Endométrio/efeitos dos fármacos , Estrogênios/toxicidade , Lactonas/toxicidade , Micotoxinas/toxicidade , Fenóis/toxicidade , Zearalenona/toxicidade , Fosfatase Alcalina/análise , Fosfatase Alcalina/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Interações Medicamentosas , Disruptores Endócrinos/toxicidade , Endométrio/citologia , Feminino , Humanos
5.
In Vivo ; 34(1): 225-231, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31882482

RESUMO

BACKGROUND/AIM: It was hypothesized that endometrial tight junction morphology and expression of tight junction proteins i.e., claudin-4 and occludin in the uterus, are affected by testosterone. Therefore, the effects of testosterone on these parameters in the uterus during receptivity period were investigated. MATERIALS AND METHODS: Ovariectomized adult female rats were given testosterone (1 mg/kg/day) alone or in combination with flutamide or finasteride between days 6 to 8 of sex-steroid replacement treatment, which was considered the period of uterine receptivity. Ultramorphology of tight junctions was visualized by transmission electron microscopy while distribution and expression of claudin-4 and occludin were examined by immunofluorescence and real-time polymerase chain reaction respectively. RESULTS: Administration of testosterone caused loss of tight junction complexity and down-regulated expression of claudin-4 and occludin in the uterus. CONCLUSION: Decreased endometrial tight junction complexity and expression of claudin-4 and occludin in the uterus during receptivity period by testosterone may interfere with embryo attachment and subsequent implantation.


Assuntos
Claudina-4/metabolismo , Endométrio/fisiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Ocludina/metabolismo , Testosterona/farmacologia , Junções Íntimas/fisiologia , Androgênios/farmacologia , Animais , Claudina-4/genética , Endométrio/efeitos dos fármacos , Feminino , Hormônios Esteroides Gonadais/metabolismo , Ocludina/genética , Ovariectomia , Ratos , Ratos Sprague-Dawley , Junções Íntimas/efeitos dos fármacos
6.
Zhonghua Fu Chan Ke Za Zhi ; 54(12): 848-853, 2019 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-31874475

RESUMO

Objective: To study influencing factors which cause the endometrial diseases in patients with breast cancer after operation. Methods: A retrospective study was performed on 212 breast cancer post-operation patients with endometrial diseases between June 2006 and January 2018 in Women's Hospital School of Medicine Zhejiang University to analyse the factors which influenced the endometrial diseases. Results: The abnormal uterine bleeding and endometrial thickness were related to the severity of endometrial disease in patients with breast cancer, and they were independent risk factors for breast cancer patients to have endometrial cancer (P<0.05) . When the diagnostic cut off value of endometrial thickness was ≥0.49 cm, the sensitivity and specificity to endometrial cancer were 78% and 25%, respectively. The average endometrial thickness was (0.56±0.39) cm in patients who were treated by selective estrogen receptor modulator (SERM) after gynecological surgery, which was significantly thicker than that of aromatase inhibitor (AI) group [ (0.33±0.23) cm] and no treatment group [ (0.44±0.28) cm, P<0.05]. The endometrial disease recurrent rate and reoperation rate in SERM group were (26.2%, 14.3%) slightly higher than that of AI group (9.5%, 4.8%) and no treatment group (21.6%, 4.9%), but there were not significant differences (all P>0.05). Conclusions: The clinical symptom of abnormal uterine bleeding and thickening endometrium are risk factors for breast cancer patients to have endometrial cancer. The endometrial thickness has high predictive value for breast cancer patients to diagnose endometrial cancer. The SERM treatment increases the endometrial thickness, recurrent rate and reoperation rate in post-operation patients.


Assuntos
Antineoplásicos Hormonais/efeitos adversos , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Hiperplasia Endometrial/induzido quimicamente , Neoplasias do Endométrio/induzido quimicamente , Endométrio/efeitos dos fármacos , Moduladores de Receptor Estrogênico/efeitos adversos , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Hemorragia Uterina/etiologia , Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Terapia Combinada , Hiperplasia Endometrial/epidemiologia , Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/patologia , Endométrio/patologia , Moduladores de Receptor Estrogênico/uso terapêutico , Feminino , Humanos , Estudos Retrospectivos , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Índice de Gravidade de Doença , Ultrassonografia
7.
Fertil Steril ; 112(6): 987-993, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31843098

RESUMO

The probability of live birth from an in vitro fertilization (IVF) cycle is modest. Many additional treatments (add-ons) are available which promise to improve the success of IVF. This review summarizes the current evidence for common IVF add-ons which are suggested to improve endometrial receptivity. Systematic reviews of randomized controlled trials and individual trials were included. Five add-ons were included: immune therapies, endometrial scratching, endometrial receptivity array, uterine artery vasodilation, and human chorionic gonadotropin instillation. The results suggest there is no robust evidence that these add-ons are effective or safe. Many IVF add-ons are costly, consuming precious resources which may be better spent on evidence-based treatments or further IVF. Large randomized controlled trials and appropriate safety assessment should be mandatory before the introduction of IVF add-ons into routine practice.


Assuntos
Implantação do Embrião/efeitos dos fármacos , Endométrio/efeitos dos fármacos , Fármacos para a Fertilidade/uso terapêutico , Fertilidade/efeitos dos fármacos , Fertilização In Vitro , Infertilidade/terapia , Endométrio/fisiopatologia , Medicina Baseada em Evidências , Feminino , Fármacos para a Fertilidade/efeitos adversos , Fertilização In Vitro/efeitos adversos , Humanos , Infertilidade/diagnóstico , Infertilidade/fisiopatologia , Nascimento Vivo , Masculino , Gravidez , Taxa de Gravidez , Resultado do Tratamento
8.
Anim Reprod Sci ; 209: 106146, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31514936

RESUMO

Cyclooxygenase-2 (COX-2) has important functions in the synthesis and release of endometrial prostaglandin F2α (PGF2α). Excessive production of COX-2 leads to an increase in endometrial PGF2α synthesis and subsequently causes luteolysis and early embryonic mortality. The aim of this study was to investigate in goats the effects of COX-2 small interference RNA (siRNA) on COX-2 mRNA abundance and the secretion of PGF2α and PGE2 in goat endometrial cells. Endometrial cells isolated from goat uteri were cultured at 38.5 °C and 5% CO2. The cells were treated with different concentrations (0, 10, 25, 50, 100, 250, 500, 750 and 1000 nM per well) of three different COX-2 siRNAs at confluency for 24 h. At 24 h post culture, COX-2 mRNA abundance was quantified using qPCR and PGF2α and PGE2 concentrations were quantified in the culture medium. There was a lesser relative abundance of COX-2 mRNA in endometrial cells at 100 to 1000 nM siRNA. The greatest extent of abundance suppression, however, was observed with 1000 nM siRNA. Transfection of COX-2 siRNA (1000 nM) to endometrial cells suppressed the COX-2 mRNA abundance by 77%, 82%, and 84% with siRNA 1, 2, 3, respectively. Furthermore, with COX-2 siRNA transfected cells, there was a lesser (P < 0.05) PGF2α concentration than in cells not transfected, whereas PGE2 secretion was not affected. The results of the study provide evidence that COX-2 siRNA used in this study suppresses COX-2 mRNA abundance and PGF2α secretion but there was no association between PGE2 concentrations and COX-2 mRNA abundance in goat endometrial epithelial cells.


Assuntos
Ciclo-Oxigenase 2/genética , Dinoprosta/metabolismo , Dinoprostona/metabolismo , Endométrio/metabolismo , Interferência de RNA/fisiologia , Animais , Células Cultivadas , Ciclo-Oxigenase 2/metabolismo , Endométrio/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Feminino , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Cabras , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/farmacologia
9.
PLoS One ; 14(9): e0222081, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31487323

RESUMO

Lipopolysaccharide (LPS) expressed on the surface of Gram-negative bacteria activates pro-inflammatory pathways, dys-regulates the function of endometrial cells and is a key player in the mechanisms involved in endometritis. This study aimed to investigate the effects of LPS on bovine endometrial epithelial cells (bEEC) from whole transcriptome with a special focus on genes involved in embryo-maternal interactions. Following in vitro culture, bEEC from three cows were exposed to 0, 2, and 8 µg/mL LPS for 24h. RNA samples extracted at 0 and 24 hours were analyzed by RNA sequencing (RNA-seq). At 24h, 2035 differentially expressed genes (DEGs) were identified between controls and samples treated with 2 µg/mL LPS. Gene ontology analysis showed that over-expressed DEGs were associated to immune response, response to stress and external stimuli, catalytic activity, and cell cycle. Genes associated with cell membrane and cell adhesion pathways were under-expressed. LPS induced changes in expression of specific genes related to embryo-maternal interactions including under-expression of eight members of the cadherin superfamily, over-expression of six members of the mucin family, and differential expression of a large set of genes binding the above molecules and of more than 20 transcripts coding for cytokines and their receptors. Type I interferon-τ dependent genes were also over-expressed. From a sub-set of 19 genes, (biological replicates of bEEC from cows taken at time 6 (n = 3), 24 (n = 6) and 48 hours (n = 3), and 2 technical replicates per sample) differential gene expression was confirmed by RT2-qPCR (r2 between fold changes at 24 hours by RT2-qPCR and RNA-seq = 0.97). These results indicate that LPS affects the function of bEEC in many ways by differential transcription, glycolytic metabolism and oxidative stress. Many transcriptomic signatures related to implantation and embryo maternal interactions were strongly affected by LPS. These results pave the way for further studies to investigate the duration of these changes and their possible impact on endometrial function and fertility.


Assuntos
Biomarcadores/análise , Implantação do Embrião/genética , Embrião de Mamíferos/metabolismo , Endométrio/metabolismo , Células Epiteliais/metabolismo , Lipopolissacarídeos/farmacologia , Transcriptoma , Animais , Bovinos , Implantação do Embrião/efeitos dos fármacos , Embrião de Mamíferos/efeitos dos fármacos , Endométrio/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Feminino , Perfilação da Expressão Gênica
10.
Res Vet Sci ; 126: 164-169, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31499425

RESUMO

Endometritis is one of the most common reproductive diseases caused by bacterial infection in the cow. Ferulic acid is a major effective component extracted from Ligusticum wallichii. Ferulic acid displays pharmacological effects such as anti-inflammation and antioxidation. The aim of the present study was to investigate the protective effects of ferulic acid on inflammation induced by lipopolysaccharide (LPS) in bovine endometrial epithelial cells (BEECs). BEECs were pretreated with ferulic acid followed by LPS treatment. QRT-PCR analysis showed the mRNA expression of LPS-induced proinflammatory cytokines (IL1B, IL6, TNFA, and IL8) was decreased with ferulic acid pretreatment. Western blot analysis showed that ferulic acid inhibited the degradation of IκB and phosphorylation of NF-κB p65. Ferulic acid suppressed the phosphorylation of MAPKs, including p38 and JNK. All of these results indicated that ferulic acid may be considered as a potential anti-inflammatory drug for curing endometritis.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Doenças dos Bovinos/tratamento farmacológico , Ácidos Cumáricos/administração & dosagem , Endometrite/veterinária , Inflamação/veterinária , Animais , Bovinos , Doenças dos Bovinos/induzido quimicamente , Endometrite/induzido quimicamente , Endometrite/tratamento farmacológico , Endométrio/efeitos dos fármacos , Endométrio/fisiopatologia , Células Epiteliais/efeitos dos fármacos , Feminino , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Lipopolissacarídeos/farmacologia , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos
11.
Anim Reprod Sci ; 208: 106128, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31405471

RESUMO

The aim was to evaluate effects of addition of pentoxifylline to skimmed milk semen extender on uterine inflammatory response. Thirty-six estrous cycles of 15 mares were randomly divided into five groups for artificial insemination (AI): Control: mimicking the AI procedure (n = 7); Extender: deposition of skimmed milk based extender (n = 7); Extender + PTX: skimmed milk based extender plus pentoxifylline (7.18 mM; n = 8); Semen: semen diluted with extender without pentoxifylline (n = 7), and Semen + PTX: semen diluted with extender containing pentoxifylline (n = 7). Mares in estrus were examined by trans-rectal palpation and using ultrasonography, and ovulation was induced. Uterine hemodynamics were assessed immediately before ovulation induction (T-30), immediately before AI (T0), 2 (T2), 6 (T6), 12 (T12), 24 (T24) and 48 (T48) h after AI. Endometrial samples were collected 6 h after AI, and slides were stained and examined to determine percentage of PMN. Pentoxifylline had no additional effect on vascular perfusion. There was a major inflammatory response with pentoxifylline treatment that was greater than that of the control group. In the group treated with Extender + PTX, there were more PMN (57.98 ±â€¯9.42%) than in the group treated with Extender (20.20 ±â€¯6.63%) and in the Semen + PTX group more PMN (82.84 ±â€¯5.71%) than in the Semen-treated group (47.83 ±â€¯10.61%). These findings indicate the addition of pentoxifylline does not stimulate blood flow; however, it induces a greater immune defense response because more neutrophils migrate to the uterine lumen.


Assuntos
Doenças dos Cavalos/prevenção & controle , Inflamação/veterinária , Pentoxifilina/farmacologia , Sêmen/efeitos dos fármacos , Doenças Uterinas/veterinária , Animais , Estudos Cross-Over , Endométrio/irrigação sanguínea , Endométrio/efeitos dos fármacos , Feminino , Cavalos , Inflamação/prevenção & controle , Inseminação Artificial/veterinária , Masculino , Leite , Ultrassonografia/veterinária , Doenças Uterinas/prevenção & controle , Vasodilatadores/farmacologia
12.
Zhonghua Fu Chan Ke Za Zhi ; 54(7): 464-469, 2019 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-31365959

RESUMO

Objective: To evaluate the effects of parthenolide on estradiol-synthesizing enzyme, steroidogenic acute regulatory protein (StAR), and ER isoforms,VEGF in human endometriotic stromal cells. Methods: Primary endometriotic stromal cells were treated with different concentrations (1, 5, 10 and 20 µmol/L) of parthenolide. The mRNA of StAR, ER isoforms (ERα and ERß), PR, vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), tumour necrosis factor-α (TNFα), tumour necrosis factor receptor (TNFR) 1, TNFR2 were measured by real-time PCR. The levels of estradiol and progesterone in the cell supernatant were measured by ELISA. Results: Different concentrations of parthenolide could up-regulate the mRNA of StAR in primary endometriotic stromal cells (F=5.722, P<0.05); the mRNA of StAR in the group of 20 µmol/L was significantly higher than that of the control group [2.6±0.3 versus 1.0, P<0.01]. Different concentrations of parthenolide could down-regulate the mRNA of ERα (F=6.921, P<0.01); the mRNA of ERα in the group of 20 µmol/L and 10 µmol/L were significantly lower than those of the control group [0.2±0.3 versus 0.3±0.3 versus 1.0, all P<0.05]. Different concentrations of parthenolide could down-regulate the ratios of ERα/ERß mRNA levels (F=4.209, P<0.05). Different concentrations of parthenolide could up-regulate the mRNA of VEGF and TNFR1 (F=10.964, P<0.01; F=7.286, P<0.01). There were no statiscal significances with different concentrations of parthenolide on the mRNA of ERß, PR, IL-6, TNFα and TNFR2, and the levels of estradiol and progesterone in the cell supernatant (all P>0.05). Conclusions: Parthenolide may regulate the expression of estradiol-synthesizing enzyme, ER isoforms and angiogenesis in endometriotic stromal cells. Parthenolide may promote the development of endometriosis.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Endometriose , Endométrio/efeitos dos fármacos , Sesquiterpenos/farmacologia , Células Estromais/metabolismo , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Endometriose/induzido quimicamente , Endometriose/genética , Endométrio/metabolismo , Endométrio/patologia , Estradiol , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Feminino , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Humanos , Isoformas de Proteínas , Células Estromais/efeitos dos fármacos , Células Estromais/patologia , Fator de Necrose Tumoral alfa/metabolismo
13.
Medicine (Baltimore) ; 98(34): e16865, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441861

RESUMO

RATIONALE: In assisted reproductive technology, a persistently thin endometrial lining represents a huge challenge during frozen embryo transfer (FET) cycles. PATIENT CONCERNS: Three patients who had a persistently thin endometrial lining despite the use of several medical agents known to improve endometrial lining thickness. DIAGNOSES: Infertility undergoing FET cycles. INTERVENTIONS: A combination of transdermal and intravaginal ozone therapy along with Pulsed Electro-Magnetic Field (PEMF) therapy. OUTCOMES: Ozone with PEMF, both of which are known to have vasodilatatory, anti-inflammatory, and anti-oxidant actions, were successful in improving the thickness of the endometrial lining in all 3 patients. Two out of 3 patients became pregnant following single embryo transfer. LESSONS: Ozone with PEMF constitute a novel experimental approach for women with persistently thin endometrial lining undergoing FET. This novel approach needs validation by large well-designed studies.


Assuntos
Endométrio/efeitos dos fármacos , Terapia de Campo Magnético , Oxidantes Fotoquímicos/administração & dosagem , Ozônio/administração & dosagem , Administração Cutânea , Administração Intravaginal , Adulto , Criopreservação , Transferência Embrionária/métodos , Endométrio/patologia , Feminino , Humanos , Oxidantes Fotoquímicos/farmacologia , Ozônio/farmacologia , Gravidez
14.
Medicina (Kaunas) ; 55(9)2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31450870

RESUMO

Background and Objectives: Assisted reproductive techniques today have helped many infertile couples achieve their desired pregnancy. However, unsuccessful implantation is usually the key failure in in vitro fertilization cycles. Many factors are now being studied to improve the implantation rate, one being endometrial artificial injury (endometrial scratching). The purpose of this study was to assess whether local endometrial artificial injury improved pregnancy rate, in long agonist and antagonist protocols. Materials and Methods: A retrospective analysis was carried out at the JSC Baltic American Clinic from January 1, 2016 to December 31, 2018. Women who were undergoing in vitro fertilization treatment were enrolled in the study. Medical data including demographic factors, menstrual history, and anamnesis of infertility were collected from medical records. Subjects were divided into intervention and control groups. The outcome of this study was clinical pregnancy rate (CPR). Results: A total of 137 women presenting with primary or secondary infertility were enrolled in the study. Clinical pregnancy was observed in 44/71 (61.9%) patients in the intervention group and 33/66 (50%) in the group without endometrial scratching (p value = 0.16). CPR in the intervention group was significantly higher in the patient group that had undergone ovarian stimulation with a long agonist protocol rather than the antagonist protocol (73.8% vs. 41.4%; p value = 0.006). In the multivariable logistic regression model, previously failed in vitro fertilization (IVF) (odds ratio (OR) = 0.07, 95% confidence interval (CI) 0.01-0.47), stimulation with the long agonist protocol (OR = 19.89, 95% CI 3.57-18.63), antagonist protocol (OR = 0.05, 95% CI 0.01-0.34), number of embryos (OR = 1.37, 95% CI 1.05-1.38), and number of blastocysts (OR = 2.96, 95% CI 1.43-8.36) remained important independent prognostic factors for clinical pregnancy. Conclusions: Our study findings indicate that randomized controlled studies are required to define patients for this procedure and to prove the effect and safety of local endometrial injury, before it is introduced to routine clinical practice.


Assuntos
Implantação do Embrião/efeitos dos fármacos , Endométrio/efeitos dos fármacos , Endométrio/lesões , Fertilização In Vitro/métodos , Infertilidade Feminina/tratamento farmacológico , Adulto , Implantação do Embrião/fisiologia , Endométrio/fisiopatologia , Feminino , Fertilização In Vitro/estatística & dados numéricos , Humanos , Infertilidade Feminina/fisiopatologia , Lituânia , Modelos Logísticos , Razão de Chances , Gravidez , Taxa de Gravidez , Estudos Retrospectivos
15.
J Endocrinol ; 243(2): 137-148, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31412315

RESUMO

Previous research on the role of insulin has focused on metabolism. This study investigated the effect of insulin on angiogenesis in endometrial decidualization. High insulin-treated mouse model was constructed by subcutaneous injection of insulin. Venous blood glucose, serum insulin, P4, E2, FSH and LH levels in the pregnant mice were detected by ELISA. Decidual markers, angiogenesis factors and decidual vascular network were detected during decidualization in the pregnant mouse model and an artificially induced decidualization mouse model. Tube formation ability and angiogenesis factors expression were also detected in high insulin-treated HUVECS cells. To confirm whether autophagy participates in hyperinsulinemia-impaired decidual angiogenesis, autophagy was detected in vivo and in vitro. During decidualization, in the condition of high insulin, serum insulin and blood glucose were significantly higher, while ovarian steroid hormones were also disordered (P < 0.05), decidual markers BMP2 and PRL were significantly lower (P < 0.05). Uterine CD34 staining showed that the size of the vascular sinus was significantly smaller than that in control. Endometrial VEGFA was significantly decreased after treatment with high insulin in vivo and in vitro (P < 0.05), whereas ANG-1 and TIE2 expression was significantly increased (P < 0.05). In addition, aberrant expression of autophagy markers revealed that autophagy participates in endometrial angiogenesis during decidualization (P < 0.05). After treatment with the autophagy inhibitor 3-MA in HUVEC, the originally damaged cell tube formation ability and VEGFA expression were repaired. This study suggests that endometrial angiogenesis during decidualization was impaired by hyperinsulinemia in early pregnant mice.


Assuntos
Endométrio/efeitos dos fármacos , Hiperinsulinismo/fisiopatologia , Insulina/administração & dosagem , Animais , Autofagia/efeitos dos fármacos , Glicemia/metabolismo , Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/fisiologia , Decídua/irrigação sanguínea , Decídua/efeitos dos fármacos , Decídua/metabolismo , Endométrio/irrigação sanguínea , Endométrio/metabolismo , Feminino , Hormônios/sangue , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/sangue , Insulina/sangue , Camundongos , Gravidez , Fator A de Crescimento do Endotélio Vascular/metabolismo
16.
J Ethnopharmacol ; 243: 112100, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31325603

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Urtica dioica L. has been used traditionally for centuries. U. dioica leaves and roots are used as a blood purifier, emmenagogue, and diuretic, as well as to treat menstrual hemorrhage, rheumatism, and eczema. The present study aimed to evaluate the activity of U. dioica L. aerial parts in endometriosis rat model. MATERIALS AND METHODS: To evaluate the effects of the plant in endometriosis, n-hexane, ethyl acetate (EtOAc), and methanol (MeOH) extracts were prepared from the aerial parts of the plant and utilized in a rat surgical endometriosis model. In this model, adhesion scores of endometriotic implants and the spherical volumes of ectopic uterine tissues were evaluated. In addition to these parameters, tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), and interleukin-6 (IL-6) levels of the peritoneal fluids were evaluated. Furthermore, histopathological studies were conducted on the endometriotic tissues. RESULTS: Post-treatment implant volumes and adhesion scores were significantly reduced in the reference and the MeOH extract treated groups. Significant differences were found between the peritoneal TNF-α, VEGF, and IL-6 levels of MeOH extract treated group and those of control group. Moreover, histopathological findings supported the biological activity results. Furthermore, isolation studies were conducted on the MeOH extract, which showed prominent activity in the rat endometriosis model. Rutin (1), isoquercetin (2), the mixture of kaempferol-3-O-rutinoside (nicotiflorin) (3a) and isorhamnetin-3-O-rutinoside (narcissin) (3b) (3), the mixture of kaempferol-3-O-glucoside (astragalin) (4a) and isorhamnetin-3-O-glucoside (4b) (4) were isolated from the active fraction. CONCLUSIONS: The present study demonstrated that aerial parts of U. dioica exhibited promising activity in the endometriosis rat model due to its flavonoids.


Assuntos
Endometriose/tratamento farmacológico , Flavonoides/uso terapêutico , Extratos Vegetais/uso terapêutico , Urtica dioica , Animais , Líquido Ascítico/efeitos dos fármacos , Líquido Ascítico/metabolismo , Modelos Animais de Doenças , Endometriose/metabolismo , Endometriose/patologia , Endométrio/efeitos dos fármacos , Endométrio/patologia , Feminino , Flavonoides/farmacologia , Interleucina-6/metabolismo , Componentes Aéreos da Planta , Extratos Vegetais/farmacologia , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
17.
Theriogenology ; 138: 137-144, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31352175

RESUMO

This study aimed to determine the effects of l-arginine (L-Arg) supplementation on steroid hormone receptors in non-pregnant ovine endometrium. All experimental ewes were randomly assigned to either a control group (n = 6), a nutrient-restricted group (n = 6), or an L-Arg supplemented nutrient-restricted group (n = 6). The effects of L-Arg on estrogen receptor α/ß (ERα/ß) and progesterone receptor (PGR) expression in the ovine endometrium were assessed. Our results showed that levels of ERß and PGR expression were significantly increased by nutrient restriction, but L-Arg counteracted the effect of nutrient restriction on ERß and PGR expression (p < 0.05). Also, expression of endometrial ERα was substantially increased (p < 0.05) by L-Arg supplementation. Furthermore, ERα/ß and PGR were mainly detected in the endometrial luminal epithelium and glandular epithelium. Therefore, we isolated and identified endometrial epithelial cells (EECs) from sheep. Different concentrations of L-Arg were added to investigate the effects on ERα/ß and PGR in EECs. The expression levels of endothelial nitric oxide synthase, ERß, and PGR were significantly increased in response to low-concentration (200 µmol) L-Arg supplementation, which subsequently decreased with a high concentration (800 µmol) (p < 0.05). Otherwise, ERα expression was remarkably increased at both L-Arg concentrations in EECs (p < 0.05). Overall, the results indicated that L-Arg performed crucial roles in the regulation of ovine steroid hormone receptor expression in the endometrium. The results of this study provide a theoretical basis and technical means for the normal function of endometrium in response to low nutrient levels.


Assuntos
Arginina/farmacologia , Restrição Calórica , Endométrio/efeitos dos fármacos , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Receptores de Progesterona/genética , Ovinos , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Restrição Calórica/veterinária , Células Cultivadas , Endométrio/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Nutrientes , Gravidez , Receptores de Progesterona/metabolismo , Ovinos/genética , Ovinos/metabolismo , Útero/efeitos dos fármacos , Útero/metabolismo
18.
Rev Assoc Med Bras (1992) ; 65(6): 857-863, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31340317

RESUMO

OBJECTIVE: To evaluate endocervical and vaginal environment changes in women using a levonorgestrel-releasing intrauterine system (LNG-IUS). METHODS: A quasi-experimental study included sixty women who had an LNG-IUS inserted in the Family Planning Clinic of UNICAMP between April and November of 2016. Women in reproductive age, non-pregnant, without the use of antibiotics and contraceptives seeking for LNG-IUS insertion were selected for this study. All women were evaluated with regard to vaginal and endocervical pH, vaginal and endocervical Gram-stained bacterioscopy, and Pap-smear before and two months after LNG-IUS insertion. Clinical aspects such as cervical mucus, vaginal discharge, and cervical ectopy were also observed. RESULTS: After LNG-IUS insertion, there was an increase in the following parameters: endocervical pH>4.5 (p=0.02), endocervical neutrophil amount (p<0.0001), vaginal cytolysis (p=0.04). There was a decrease in vaginal discharge (p=0.01). No statistically significant changes were found in vaginal pH, neutrophils amount in the vaginal mucosa, vaginal discharge appearance, vaginal candidiasis, bacterial vaginosis, vaginal coccobacillary microbiota, cervical mucus appearance, or cervical ectopy size. CONCLUSIONS: Short-term LNG-IUS use did not increase vulvovaginal candidiasis or bacterial vaginosis, and led to diminished vaginal discharge. Notwithstanding, this device promoted reactional changes in the vaginal and endocervical environment, without modification on cervical ectopy size.


Assuntos
Colo do Útero/efeitos dos fármacos , Anticoncepcionais Femininos/efeitos adversos , Endométrio/efeitos dos fármacos , Dispositivos Intrauterinos Medicados/efeitos adversos , Levanogestrel/efeitos adversos , Vagina/efeitos dos fármacos , Adolescente , Adulto , Colo do Útero/microbiologia , Endométrio/microbiologia , Feminino , Humanos , Pessoa de Meia-Idade , Teste de Papanicolaou , Estatísticas não Paramétricas , Fatores de Tempo , Vagina/química , Vagina/microbiologia , Esfregaço Vaginal , Adulto Jovem
19.
Drug Des Devel Ther ; 13: 1855-1863, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31239640

RESUMO

Purpose: The two major ovarian-stimulation protocols for in vitro fertilization are gonadotropin-releasing hormone agonist (GnRH-a) protocol or GnRH antagonist (GnRH-ant) protocol; however, comparisons of their relative efficacy remain controversial. Additionally, conflicting data exist regarding their effects on endometrial receptivity. Thus, this study investigated how GnRH-a and GnRH-ant treatments alter the endometrium during the mid-secretory phase. Patients and methods: We compared proteomic profiles across human endometrium tissues of mid-secretory phase from normal control humans (n=5), patients treated with GnRH-a (n=5), and patients treated with GnRH-ant (n=5). Results: We identified 2088 proteins, with 362 that exhibited significantly different expression. Fuzzy c-means clustering (FCM) using the M Fuzz algorithm analysis showed that the same 87 proteins changed significantly in both the GnRH-a and GnRH-ant groups compared with those in the control. Moreover, Gene Ontology (GO) analysis showed that, of these 87, downregulated proteins were associated with energy metabolism and upregulated proteins were linked to cytoskeleton maintenance. Upregulated proteins involved in complement-mediated immunity were present in 151 proteins that exhibited significantly different expression in the GnRH-ant group only. Conclusion: We demonstrated that comparative proteomic analysis is useful for accessing endometrial receptivity, which seemed more strongly impaired by GnRH-ant than GnRH-a treatments. Our findings also revealed that energy metabolism and immunity response may be the key biological mechanisms underlying human endometrial receptivity.


Assuntos
Endométrio/efeitos dos fármacos , Doenças das Tubas Uterinas/tratamento farmacológico , Hormônio Liberador de Gonadotropina , Antagonistas de Hormônios/farmacologia , Proteômica , Adulto , Algoritmos , Análise por Conglomerados , Endométrio/patologia , Doenças das Tubas Uterinas/patologia , Feminino , Hormônio Liberador de Gonadotropina/agonistas , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Humanos
20.
Fertil Steril ; 112(3): 503-509.e1, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31248618

RESUMO

OBJECTIVE: To evaluate whether the change in endometrial thickness between the end of the estrogen phase and the day of embryo transfer has an impact on the pregnancy rate in frozen-thawed embryo transfer (FET) cycles. DESIGN: Retrospective observational cohort study. SETTING: Single tertiary care medical center. PATIENT(S): Ultrasound images in 274 FET cycles were reviewed. All patients underwent endometrial preparation with the use of hormonal therapy. INTERVENTIONS(S): Ultrasound measurements of endometrial thickness at the end of the estrogen phase and the day of embryo transfer. MAIN OUTCOME MEASURE(S): The change in endometrial thickness and ongoing pregnancy rate. RESULT(S): We calculated the ongoing pregnancy rate in patients whose endometrial thickness decreased (compacted) after starting progesterone by 5%, 10%, 15%, or 20% compared with patients with no change or increased endometrial thickness. The ongoing pregnancy rate was significantly increased at all levels of compaction compared with no compaction. The ongoing pregnancy rate showed a significant increase with each decreasing quartile of change in thickness (increased percentage of compaction) in the progesterone phase compared with the estrogen phase. CONCLUSION(S): There is a highly significant inverse correlation between the ongoing pregnancy rate and the change of endometrial thickness between the end of estrogen administration and the day of embryo transfer.


Assuntos
Transferência Embrionária/métodos , Endométrio/efeitos dos fármacos , Endométrio/diagnóstico por imagem , Resultado da Gravidez/epidemiologia , Progesterona/administração & dosagem , Estudos de Coortes , Transferência Embrionária/tendências , Endométrio/fisiologia , Feminino , Humanos , Tamanho do Órgão/efeitos dos fármacos , Tamanho do Órgão/fisiologia , Gravidez , Estudos Retrospectivos
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