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1.
Reproduction ; 159(4): 453-463, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31990677

RESUMO

The differentiation of endometrial stromal cells (ESC), named decidualization, is essential to regulate trophoblast invasion and to support pregnancy establishment and progression. Decidualization follows ESC proliferation and it has been described that cell cycle arrest contributes to a proper decidualization. Interestingly, resveratrol, a natural compound derived from grapes with antioxidant properties, has been widely studied in relation to endometrial health. However, little is known about the effect of resveratrol supplementation during decidualization. Therefore, in this study we evaluate the effect of resveratrol supplementation during decidualization. We used primary and immortalized human ESC and we decidualized them in vitro with a decidualization cocktail containing medroxyprogesterone acetate, estradiol and 8-Bromo-cyclic AMP. Pre-decidualized cells were further treated with the decidualization cocktail supplemented with resveratrol. Our results show that resveratrol supplementation increased, in a dose-dependent manner, the expression levels of prolactin and IGFBP1 (RT-PCR and ELISA), indicating an enhanced in vitro decidualization of human ESC. This enhanced decidualization was accompanied by a decrease in cell proliferation (crystal violet and CellTiter proliferation assay) and by changes in the mRNA levels of key cell cycle regulators (RT-PCR). Furthermore, resveratrol supplementation seemed to enhance decidualization by reinforcing the effect of the decidualization cocktail. We believe that resveratrol could to be an effective supplementation to reinforce hormone action during human ESC decidualization and that further insights into resveratrol action and its interaction with estradiol and progesterone signaling pathways could facilitate the identification of new therapeutic strategies for the improvement of women's health.


Assuntos
Antioxidantes/farmacologia , Decídua/efeitos dos fármacos , Resveratrol/farmacologia , Adulto , Antioxidantes/uso terapêutico , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular , Decídua/citologia , Decídua/metabolismo , Suplementos Nutricionais , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Distúrbios Menstruais/terapia , Cultura Primária de Células , Resveratrol/uso terapêutico , Células Estromais/efeitos dos fármacos
2.
Fertil Steril ; 112(5): 947-958.e3, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31371049

RESUMO

OBJECTIVE: To investigate whether phytoestrogens (genistein and daidzein) alter in vitro decidualization of human endometrial stromal cells (ESCs). DESIGN: Isolated primary ESCs were exposed to phytoestrogens and decidualized in vitro. SETTING: Academic fertility center. PATIENT(S): Twenty fertile oocyte donors attending the IVI Valencia clinic. INTERVENTION(S): Treatment of ESC with phytoestrogens at 0, 10, 20, 50, and 100 µM. MAIN OUTCOME MEASURE(S): The ESC proliferation was analyzed by MTS assay. In vitro decidualization was induced in the presence of phytoestrogens by medroxyprogesterone acetate/cyclic adenosine 3':5' monophosphate and evaluated by prolactin (PRL) ELISA and F-actin immunostaining. The Ki67 proliferative marker was analyzed by immunofluorescence. The ESC apoptosis was assessed by annexin V/propidium iodide detection using flow cytometry. Estrogen (ERß) and P receptor (PR) localization were evaluated by immunofluorescence. RESULT(S): The ESC exposed to 0, 19, 20, 50, and 100 µM of genistein, daidzein, and genistein + daidzein showed a dose-dependent proliferation decrease. After 48-96 hours of culture, this reduction was significant in the presence of 50 µM of phytoestrogens versus 10 µM untreated ESC. The ESC decidualized in the presence of phytoestrogens did not rearrange their cytoskeletons and showed a significant decrease in PRL secretion compared with untreated decidualized ESCs (dESCs). However, phytoestrogens did not alter proliferative status or the percentage of viable/apoptotic cells in dESC compared with untreated dESC. During decidualization, phytoestrogens induced the same nuclear translocation of ERß and PR as the control dESC. CONCLUSION(S): This study reveals that high doses of phytoestrogens could affect the in vitro decidualization process.


Assuntos
Endométrio/efeitos dos fármacos , Genisteína/farmacologia , Isoflavonas/farmacologia , Fitoestrógenos/farmacologia , Células Estromais/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Células Cultivadas , Decídua/citologia , Decídua/efeitos dos fármacos , Decídua/fisiologia , Relação Dose-Resposta a Droga , Endométrio/citologia , Endométrio/fisiologia , Feminino , Humanos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Células Estromais/fisiologia
3.
Reprod Sci ; 25(11): 1577-1588, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29455621

RESUMO

BACKGROUND: To induce endometrial decidualization in rodents, an intrauterine oil stimulus can be delivered via the nontraumatic vagina or via the traumatic laparotomy. However, there is considerable variation in amount of decidualization using these inducing methods. Therefore, we studied which oil delivery route could achieve the highest rate of endometrial decidualization along the full length of both uterine horns. METHODS: To induce decidualization, ovariectomized C57Bl/6J mice were injected with estrogen (100 ng/day; 3 days). A progesterone pellet (5 mg) was implanted subcutaneously, followed by estrogen injections (5 ng/day; 3 days). Oil (20 µL/horn) was injected in the uterus via laparotomy, laparoscopy, or vagina. Four days later, the pellet was removed, followed by hysterectomy after 4 to 6 hours. Endometrial decidualization was evaluated macroscopically and microscopically using hematoxylin and eosin and desmin staining. Furthermore, uterine weight and hormone levels were measured. RESULTS: The proportion of animals with macroscopic bicornuate decidualization was higher after laparoscopic (83%) and laparotomic (89%) injection than after sham injection (11%). Furthermore, macroscopic bicornuate decidualization was significantly higher after laparotomic injection (89%) compared to the vaginal injection (38%). Uterine weight and endometrial surface area were significantly higher in both laparotomy and laparoscopy groups compared to the sham group, while the relative desmin-positive endometrial surface area was only significantly different between the laparotomy and the sham animals. CONCLUSION: Methods using laparoscopic and laparotomic intrauterine oil injection resulted in a higher amount of decidualized endometrium compared to sham injection, although further optimization is needed to reach full bicornuate decidualization.


Assuntos
Decídua/efeitos dos fármacos , Endometriose/induzido quimicamente , Menstruação , Óleo de Gergelim/administração & dosagem , Animais , Decídua/citologia , Modelos Animais de Doenças , Estrogênios/administração & dosagem , Estrogênios/sangue , Feminino , Laparoscopia , Laparotomia , Camundongos Endogâmicos C57BL , Progesterona/administração & dosagem , Progesterona/sangue
4.
Fertil Steril ; 109(4): 728-734.e2, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29397924

RESUMO

OBJECTIVE: To investigate the impact of the androgen precursor dehydroepiandrosterone (DHEA) on the decidualization of human endometrial stromal cells isolated from women of advanced reproductive age. DESIGN: In vitro study. SETTING: University research institute. PATIENT(S): Proliferative phase primary human endometrial stromal fibroblasts (hESFs) were isolated from women of advanced reproductive age (n = 16; mean age, 44.7 ± 2.3). None of the women were receiving hormone therapy or had endometriosis. INTERVENTION(S): Isolated hESFs were decidualized in vitro by incubation with P (1 µM) and cAMP (0.1 mg/mL) in the presence, or absence, of DHEA (10 nM, 100 nM). MAIN OUTCOME MEASURE(S): Secretion of androgens was assessed by ELISA. Expression of decidualization markers and endometrial receptivity markers was assessed by quantitative polymerase chain reaction and ELISA. RESULT(S): Decidualization responses were retained in hESF isolated from women of advanced reproductive age. Supplementation with DHEA increased androgen biosynthesis and concentrations of T and dihydrotestosterone were ∼3× greater after coincubation with DHEA compared with hESF stimulated with decidualization alone. Addition of DHEA to decidualized hESF increased expression of the decidualization markers IGFBP1 and PRL and the endometrial receptivity marker SPP1. DHEA enhanced secretion of IGFBP1, PRL, and SPP1 proteins maximally by day 8 of the decidualization time course concomitant with peak androgen concentrations. CONCLUSION(S): These novel results demonstrate DHEA can enhance in vitro decidualization responses of hESF from women of advanced reproductive age. Supplementation with DHEA during the receptive phase may augment endometrial function and improve pregnancy rates in natural or assisted reproductive cycles.


Assuntos
Proliferação de Células/efeitos dos fármacos , Decídua/efeitos dos fármacos , Desidroepiandrosterona/farmacologia , Fibroblastos/efeitos dos fármacos , Idade Materna , Saúde Reprodutiva , Células Estromais/efeitos dos fármacos , Adulto , Biomarcadores/metabolismo , Células Cultivadas , Decídua/citologia , Decídua/metabolismo , Di-Hidrotestosterona/metabolismo , Feminino , Fibroblastos/metabolismo , Humanos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Pessoa de Meia-Idade , Osteopontina/metabolismo , Prolactina/metabolismo , Células Estromais/metabolismo , Fatores de Tempo
5.
Fitoterapia ; 113: 58-63, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27370099

RESUMO

Recurrent spontaneous abortion (RSA) is a common clinical condition, but its reasons remain unknown in 37-79% of the affected women. The steroid hormone progesterone (P4) is an integral mediator of early pregnancy events, exerting its effects via the progesterone receptor (PR). Dipsaci Radix (DR) has long been used for treating gynecological diseases in Chinese medicine, while its molecular mechanisms and active ingredients are still unclear. We report here the progesterone-like effects of the alcohol extraction and Asperosaponin VI from DR in primary decidual cells and HeLa cell line. We first determined the safe concentration of Asperosaponin VI in the cells with MTT assay and then found by using dual luciferase reporter and Western blotting that Asperosaponin VI significantly increased PR expression. Moreover, we explored the mechanisms of action of the DR extracts and Asperosaponin VI, and the results showed that they could activate Notch signaling, suggesting that they may function by promoting decidualization.


Assuntos
Decídua/efeitos dos fármacos , Receptores Notch/metabolismo , Receptores de Progesterona/metabolismo , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Decídua/citologia , Dipsacaceae/química , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Células HeLa , Humanos , Raízes de Plantas/química , Gravidez , Cultura Primária de Células
6.
J Ethnopharmacol ; 150(3): 907-17, 2013 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-24140602

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Excessive uterine bleeding is the most common and problematic side effect of RU486 medical abortion. Shenghua Decoction (SHD) is a well-known traditional Chinese herbal prescription for reducing uterine bleeding induced by RU486 medical abortion. However, its therapeutic mechanism still remains unclear. The Th1/Th2/Th17/Treg paradigm plays an important role in achieving maternal-fetal immunotolerance and its bias participates in RU486-induced abortion. Our previous research on mice demonstrated that the uterine bleeding volume is negatively related to the proportions of Th1 and Th17 cells whereas positively related to the proportions of Th2 and Treg cells. Additionally, Th1-type cytokine inducing effect was identified in our previous study. Therefore, it was hypothesized that SHD reduced the uterine bleeding in RU486 medical abortion by inducing Th1/Th2/Th17/Treg paradigm bias. The purpose of this study was to determine the regulatory effect and the mechanism of SHD on human decidual Th1/Th2/Th17/Treg paradigm for alleviating uterine bleeding in RU486 medical abortion. MATERIALS AND METHODS: 90 women within seven weeks of a normal intrauterine pregnancy, who elected for termination of pregnancy, were divided into three groups; vacuum aspiration group, RU486 group, and SHD-RU486 group. Duration of uterine bleeding was recorded and volume of uterine bleeding was measured by the method of alkaline hematin photometric. To determine the regulatory effect of SHD on Th1/Th2/Th17/Treg paradigm, the proportions of Th1/Th2/Th17/Treg cells in the decidua of different groups were analyzed using a FACS calibur. Correlation was analyzed in order to demonstrate the relationship between the Th1/Th2/Th17/Treg paradigm and the uterine bleeding in RU486 medical abortion. Moreover, to elucidate the mechanism underlying the T-cell paradigm regulating of SHD, the mRNA and protein expressions of subset-specific transcription factors (T-bet, GATA-3, RORγt, and Foxp3) for the differentiation of Th1/Th2/Th17/Treg paradigm in human decidual CD4(+) T cells were detected by reverse transcription-polymerase chain reaction (RT-PCR) assay and western blot analysis respectively. Moreover, the mRNA expression of the characteristic cytokines of Th1/Th2/Th17/Treg paradigm (IFNγ, IL-4, IL-17A, TGF-ß) were analyzed by RT-PCR assay. RESULT: Compared with RU486 group, both the uterine bleeding volume and duration reduced significantly in SHD-RU486 group. Both the duration and the volume of the uterine bleeding demonstrated negative correlation with the proportions of Th1 and Th17 cells, whereas showed positive correlation with Th2 and Treg cells. SHD increased the proportions of Th1 and Th17 cells whereas decreased those of Th2 and Treg cells. Thus, the ratios of Th1/Th2 and Th17/Treg cells elevated markedly after SHD treatment. SHD promoted the mRNA as well as the protein expressions of subset-specific transcription factors for the differentiation of Th1 and Th17 subsets (T-bet and RORγt) while inhibited those of Th2 and Treg cells (GATA-3 and Foxp3). Moreover, the mRNA expression of Th1- and Th17- type cytokines (IFNγ and IL-17A) was up-regulated while that of Th2-type and Treg-produced cytokines (IL-4 and TGF-ß) was down-regulated significantly after SHD administration. CONCLUSION: Th1/Th2/Th17/Treg paradigm bias was involved in RU486 medical abortion. SHD reduced the uterine bleeding efficiently by inducing Th1 and Th17 skews in the maternal-fetal of RU486 medical abortion patients. The regulatory effect of SHD on Th1/Th2/Th17/Treg paradigm in RU486 medical abortion is attributed to the modulation of transcription and protein expression of subset-specific transcription factors for T-cell subsets differentiation and their characteristic cytokines.


Assuntos
Aborto Induzido/efeitos adversos , Decídua/efeitos dos fármacos , Medicamentos de Ervas Chinesas/uso terapêutico , Linfócitos T/efeitos dos fármacos , Hemorragia Uterina/tratamento farmacológico , Abortivos Esteroides/efeitos adversos , Adulto , Citocinas/genética , Citocinas/imunologia , Decídua/citologia , Decídua/imunologia , Decídua/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Fatores de Transcrição Forkhead/metabolismo , Fator de Transcrição GATA3/metabolismo , Humanos , Mifepristona/efeitos adversos , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Gravidez , Proteínas com Domínio T/metabolismo , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Hemorragia Uterina/etiologia , Hemorragia Uterina/imunologia , Hemorragia Uterina/metabolismo , Adulto Jovem
7.
PLoS One ; 8(10): e76605, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24098539

RESUMO

Extravillous trophoblasts (EVTs) characterize the invasion of the maternal decidua under low oxygen and poor nutrition at the early feto-maternal interface to establish a successful pregnancy. We previously reported that autophagy in EVTs was activated under 2% O2 in vitro, and autophagy activation was also observed in EVTs at the early feto-maternal interface in vivo. Here, we show that autophagy is an energy source for the invasion of EVTs. Cobalt chloride (CoCl2), which induces hypoxia inducible factor 1α (HIF1α) overexpression, activated autophagy in HTR8/SVneo cells, an EVT cell line. The number of invading HTR8-ATG4B(C74A) cells, an autophagy-deficient EVT cell line, was markedly reduced by 81 percent with the CoCl2 treatment through the suppression of MMP9 level, although CoCl2 did not affect the cellular invasion of HTR8-mStrawberry cells, a control cell line. HTR8-ATG4B(C74A) cells treated with CoCl2 showed a decrease in cellular adenosine triphosphate (ATP) levels and a compensatory increase in the expression of purinergic receptor P2X ligand-gated ion channel 7 (P2RX7), which is stimulated with ATP, whereas HTR8-mStrawberry cells maintained cellular ATP levels and did not affect P2RX7 expression. Furthermore, the decreased invasiveness of HTR8-ATG4B(C74A) cells treated with CoCl2 was neutralized by ATP supplementation to the level of HTR8-ATG4B(C74A) cells treated without CoCl2. These results suggest that autophagy plays a role in maintaining homeostasis by countervailing HIF1α-mediated cellular energy consumption in EVTs.


Assuntos
Trifosfato de Adenosina/metabolismo , Autofagia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Trofoblastos/metabolismo , Adesão Celular , Linhagem Celular , Movimento Celular , Cobalto/farmacologia , Decídua/citologia , Decídua/metabolismo , Metabolismo Energético , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/agonistas , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Gravidez , Primeiro Trimestre da Gravidez , Receptores Purinérgicos P2X7/genética , Receptores Purinérgicos P2X7/metabolismo , Transdução de Sinais , Trofoblastos/citologia
8.
Biol Reprod ; 89(4): 86, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23946541

RESUMO

All mammalian uteri have luminal (LE) and glandular epithelia (GE) in their endometrium. The LE mediates uterine receptivity and blastocyst attachment for implantation, and the GE synthesize and secrete or transport bioactive substances involved in blastocyst implantation, uterine receptivity, and stromal cell decidualization. However, the mechanisms governing uterine epithelial development after birth and their function in the adult are not fully understood. Here, comprehensive microarray analysis was conducted on LE and GE isolated by laser capture microdissection from uteri on Postnatal Day 10 (PD 10) and day of pseudopregnancy (DOPP) 2.5 and 3.5. This data was integrated with analysis of uteri from gland-containing control and aglandular progesterone-induced uterine gland knockout mice from PD 10 and DOPP 3.5. Many genes were expressed in both epithelia, but there was greater expression of genes in the LE than in the GE. In the neonate, GE-expressed genes were enriched for morphogenesis, development, migration, and retinoic acid signaling. In the adult, LE-expressed genes were enriched for metabolic processes and steroid biosynthesis, whereas retinoid signaling, tight junction, extracellular matrix, and regulation of kinase activity were enriched in the GE. The transcriptome differences in the epithelia support the idea that each cell type has a distinct and complementary function in the uterus. The candidate genes and regulatory networks identified here provide a framework to discover new mechanisms regulating development of epithelia in the postnatal uterus and their functions in early pregnancy.


Assuntos
Envelhecimento , Endométrio/citologia , Endométrio/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Transcrição Gênica , Transcriptoma , Animais , Animais Recém-Nascidos , Decídua/citologia , Decídua/efeitos dos fármacos , Decídua/crescimento & desenvolvimento , Decídua/metabolismo , Endométrio/efeitos dos fármacos , Endométrio/crescimento & desenvolvimento , Feminino , Fármacos para a Fertilidade Feminina/farmacologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Técnicas de Inativação de Genes , Microdissecção e Captura a Laser , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Análise de Sequência com Séries de Oligonucleotídeos , Progesterona/farmacologia , Pseudogravidez/induzido quimicamente , Pseudogravidez/metabolismo , Transcrição Gênica/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Útero/citologia , Útero/efeitos dos fármacos , Útero/crescimento & desenvolvimento , Útero/metabolismo
9.
Stem Cells Dev ; 22(6): 964-74, 2013 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-23216285

RESUMO

Despite being a histologically dynamic organ, mechanisms coordinating uterine regeneration during the menstrual/estrous cycle and following parturition are poorly understood. In the current study, we hypothesized that endometrial epithelial tissue regeneration is accomplished, in part, by mesenchymal-to-epithelial transition (MET). To test this hypothesis, fate mapping studies were completed using a double transgenic (Tg) reporter strain, Amhr2-Cre; Rosa26-Stop(fl/fl-EYFP) (i.e., flox-stop EYFP reporter). EYFP expression was observed in Müllerian duct mesenchyme-derived stroma and myometrium, but not epithelia in young and peripubertal double Tg female mice. However, mosaic EYFP expression was observed in epithelia of double Tg mice after parturition. To ensure the observed epithelial EYFP expression was not due to leaky Amhr2 promoter activity, resulting in aberrant Cre expression, transgenic mice expressing LacZ under the control of the Amhr2 promoter (Amhr2-LacZ) were used to monitor ß-galactosidase (ß-Gal) activity within the uterus. ß-Gal activity was not detected in luminal or glandular epithelia regardless of age, reproductive status, or degree of damage incurred within the uterus. Lastly, a unique population of transitional cells was identified that expressed the epithelial cell marker, pan-cytokeratin, and the stromal cell marker, vimentin. These cells localized predominantly to the regeneration zone in the mesometrial region of the endometrium. These findings suggest a previously unappreciated role for MET in endometrial regeneration and have important implications for proliferative diseases of the endometrium such as endometriosis.


Assuntos
Decídua/fisiologia , Animais , Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/genética , Transdiferenciação Celular , Decídua/citologia , Decídua/efeitos dos fármacos , Endométrio/citologia , Endométrio/efeitos dos fármacos , Endométrio/fisiologia , Ciclo Estral , Feminino , Expressão Gênica , Genes Reporter , Humanos , Proteínas Luminescentes/biossíntese , Proteínas Luminescentes/genética , Masculino , Camundongos , Camundongos Transgênicos , Microscopia de Fluorescência , Regiões Promotoras Genéticas , Receptores de Peptídeos/genética , Receptores de Fatores de Crescimento Transformadores beta/genética , Regeneração , Óleo de Gergelim/farmacologia
10.
Proc Natl Acad Sci U S A ; 106(30): 12542-7, 2009 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-19620711

RESUMO

Implantation is initiated when the embryo attaches to the uterine luminal epithelium during early pregnancy. Following this event, uterine stromal cells undergo steroid hormone-dependent transformation into morphologically and functionally distinct decidual cells in a unique process known as decidualization. An angiogenic network is also formed in the uterine stromal bed, critically supporting the early development of the embryo. The steroid-induced mechanisms that promote stromal differentiation and endothelial proliferation during decidualization are not fully understood. Although the role of ovarian progesterone as a key regulator of decidualization is well established, the requirement of ovarian estrogen (E) during this process remains unresolved. Here we show that the expression of P450 aromatase, a key enzyme that converts androgens to E, is markedly induced in mouse uterine stromal cells undergoing decidualization. The aromatase then acts in conjunction with other steroid biosynthetic enzymes present in the decidual tissue to support de novo synthesis of E. This locally produced E is able to support the advancement of the stromal differentiation program even in the absence ovarian E in an ovariectomized, progesterone-supplemented pregnant mouse model. Administration of letrozole, a specific aromatase inhibitor, to these mice blocked the stromal differentiation process. Gene expression profiling further revealed that the intrauterine E induces the expression of several stromal factors that promote neovascularization in the decidual tissue. Collectively, these studies identified the decidual uterus as a novel site of E biosynthesis and uncovered E-regulated maternal signaling pathways that critically control uterine differentiation and angiogenesis during early pregnancy.


Assuntos
Decídua/metabolismo , Estrogênios/biossíntese , Neovascularização Fisiológica , Útero/metabolismo , Animais , Aromatase/genética , Aromatase/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Decídua/irrigação sanguínea , Decídua/citologia , Implantação do Embrião , Feminino , Regulação da Expressão Gênica no Desenvolvimento/genética , Imuno-Histoquímica , Masculino , Camundongos , Ovariectomia , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Gravidez , Progesterona/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Estromais/metabolismo , Útero/irrigação sanguínea , Útero/citologia
11.
Am J Obstet Gynecol ; 195(6): 1693-9, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16792994

RESUMO

OBJECTIVE: The objective of this study was to determine the effect of omega-3 fatty acids (eicosapentaenoic acid [EPA]; docosahexaenoic acid [DHA]) on prostaglandin production and prostanoid enzyme expression in cultured decidual cells exposed to interleukin-1beta (IL-1beta), a cytokine that plays a major role in inflammation. STUDY DESIGN: Decidua was obtained from human placentas of nonlaboring patients at term cesarean delivery (N = 6) and cultured by using standard cell culture techniques. Cells were preincubated in defined media with various concentrations of vehicle, DHA, or EPA for 1 hour. IL-1beta (10 ng/mL) was then added to the media, and experiments were terminated 12 hours after exposure to IL-1beta. Prostaglandin E2 (PGE2) and PGF2alpha concentrations in conditioned media were measured by enzyme-linked immunosorbent assay; cyclooxygenase-1 (COX-1), COX-2, microsomal prostaglandin E synthase (mPGES)-1, mPGES-2, and 15-hydroxy prostaglandin dehydrogenase (PGDH) expression were quantified by real-time polymerase chain reaction and immunoblotting. Groups were compared with the use of Student t test, with significance defined as P < .05. RESULTS: Preincubation with DHA decreased prostaglandin production by up to 80% when compared with controls. DHA decreased both mPGES-1 and -2 messenger RNA expression by approximately 50% (P = .02). Preincubation in DHA or EPA had no effect on COX-1, COX-2, and PGDH messenger RNA or protein expression. CONCLUSION: Under conditions simulating inflammation, supplementation with omega-3 fatty acids decreases PGE2 and PGF2alpha production in cultured decidual cells. The reduction in prostaglandin production was associated with a decreased expression of mPGES-1 and -2. These findings suggest a mechanism by which omega-3 fatty acid supplementation decreases the incidence of preterm birth in high-risk patients.


Assuntos
Decídua/metabolismo , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/farmacologia , Mediadores da Inflamação/farmacologia , Interleucina-1beta/farmacologia , Antagonistas de Prostaglandina/farmacologia , Prostaglandinas/biossíntese , Células Cultivadas , Decídua/citologia , Feminino , Humanos , Oxirredutases Intramoleculares/genética , Microssomos/enzimologia , Gravidez , Prostaglandina-E Sintases , RNA Mensageiro/antagonistas & inibidores
12.
Fitoterapia ; 72(4): 435-7, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11395273

RESUMO

Three triterpenoid acids, nigranoic acid (1), manwuweizic acid (2), schisandronic acid (3), and other four compounds were isolated from the stems of Schisandra propinqua. Compounds 1 and 2 showed significant cytotoxic effect against human decidual cells and rat luteal cells in vitro.


Assuntos
Decídua/efeitos dos fármacos , Células Lúteas/efeitos dos fármacos , Magnoliopsida , Plantas Medicinais , Triterpenos/farmacologia , Animais , Células Cultivadas/efeitos dos fármacos , Decídua/citologia , Feminino , Humanos , Células Lúteas/citologia , Extratos Vegetais/farmacologia , Caules de Planta , Gravidez , Ratos , Ratos Sprague-Dawley
13.
J Mol Endocrinol ; 22(1): 91-101, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9924184

RESUMO

In the mouse, the attachment reaction between the blastocyst trophectoderm and the receptive uterine luminal epithelium occurs at 2200-2300 h on day 4 of pregnancy and is rapidly followed by transformation of stromal cells into decidual cells (decidual cell reaction). This process can also be induced experimentally (deciduoma) by intraluminal oil infusion in the uterus on day 4 of pseudopregnancy. The decidual cell reaction is associated with up- and down-regulation of many genes in a cell-specific manner. Using mRNA differential display, we identified cyclin D3 as one of the genes that is upregulated in the uterus at the sites of blastocyst apposition during the attachment reaction. The levels of expression were low in the morning of days 1-4 as determined by Northern hybridization. In situ hybridization analysis showed that on days 1 and 2, signals were primarily localized in uterine epithelial cells, while signals were detected in both the stromal and epithelial cells on days 3 and 4. In contrast, with the initiation and progression of decidualization on days 5, 6 and 7, the levels of cyclin D3 mRNA were remarkably upregulated in stromal cells both at the mesometrial and the antimesometrial poles. However, on day 8, signals were primarily localized in stromal cells at the mesometrial decidual bed. Implanting blastocysts on these days also expressed cyclin D3 mRNA. In the progesterone-treated delayed implanting mice, the uterine levels of cyclin D3 mRNA were modest at the sites of blastocyst apposition, but were upregulated with the onset of implantation by estradiol-17beta. However, the decidual expression of cyclin D3 mRNA was not dependent on the presence of blastocysts, since increased expression also occurred in experimentally induced deciduoma in the absence of blastocysts. The importance of cyclin D3 in decidualization was further examined in Hoxa-10-deficient mice which show defective decidualization. The expression of cyclin D3 mRNA in Hoxa-10(-/-) uteri on day 5 was severely compromised after application of a deciduogenic stimulus on day 4 of pseudopregnancy. Collectively, the results suggest that cyclin D3 could be important for the process of decidualization.


Assuntos
Ciclinas/fisiologia , Decídua/crescimento & desenvolvimento , Proteínas de Homeodomínio , Prenhez/fisiologia , Útero/metabolismo , Animais , Blastocisto/fisiologia , Ciclina D3 , DNA Complementar/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/fisiologia , Decídua/citologia , Implantação do Embrião/fisiologia , Células Epiteliais/metabolismo , Feminino , Proteínas Homeobox A10 , Hibridização In Situ , Camundongos , Camundongos Knockout , Técnicas de Sonda Molecular , Reação em Cadeia da Polimerase , Gravidez , Pseudogravidez/metabolismo , RNA Mensageiro/biossíntese , Óleo de Gergelim/farmacologia , Células Estromais/metabolismo , Técnica de Subtração , Útero/citologia , Útero/efeitos dos fármacos
14.
J Endocrinol ; 110(1): 93-6, 1986 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-3734678

RESUMO

Ovariectomized mice were treated with oestrogen and progesterone on a schedule to mimic early pregnancy. Decidualization was induced with oil and uteri were examined at various times after the last progesterone injection. The first morphological change detected in the uterus of decidualized mice following withdrawal of progesterone was infiltration of leucocytes into the stroma. This preceded overt tissue breakdown and extravasation of blood cells, and did not occur following withdrawal of progesterone without decidualization. It is suggested either that there is a release of a chemoattractant from decidual cells before any morphological changes are apparent or that the signal for attracting the leucocytes is released at the time of decidual induction, but that their migration is suppressed by progesterone.


Assuntos
Decídua/fisiologia , Leucócitos/fisiologia , Óleos de Plantas , Animais , Movimento Celular , Decídua/citologia , Estradiol/farmacologia , Feminino , Camundongos , Modelos Biológicos , Óleos/farmacologia , Ovariectomia , Óleo de Amendoim , Gravidez , Progesterona/farmacologia , Útero/citologia , Útero/efeitos dos fármacos
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