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1.
Front Endocrinol (Lausanne) ; 15: 1346084, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38572478

RESUMEN

Objective: A Mediterranean dietary pattern, sleeping habits, physical activity, and lifestyle appear to affect reproductive health. There are few reports about whether fertility-specific quality of life (QOL) is linked to infertility treatment outcomes. The aim of this study is to investigate when lifestyle factors and fertility-specific QOL are comprehensively considered, which factors influence assisted reproductive technology (ART) outcomes. Methods: This prospective cohort includes 291 women undergoing a first ART treatment at multiple centers in Japan and was designed to evaluate the influence of diet, physical activity, sleeping pattern, computer use duration, and fertility-specific quality of life tool (FertiQoL) score on ART treatment outcomes using a questionnaire. The primary endpoint was the good-quality blastocyst rate per oocyte retrieval and the secondary endpoints were a positive pregnancy test and gestational sac (GS) detection. Results: The good-quality blastocyst rate per oocyte retrieval tended to be negatively associated with frequent fish consumption. After all embryo transfer (ET) cycles, a positive pregnancy test tended to be positively associated with longer sleep and longer computer use (OR = 1.6, 95% CI = 0.9-2.7 and OR = 1.7, CI = 1.0-2.8, respectively) and negatively associated with a smoking partner (OR = 0.6, CI = 0.3-1.0). GS detection was positively and significantly associated with frequent olive oil intake and longer computer use (OR = 1.7, CI = 1.0-3.0 and OR = 1.7, CI = 1.0-3.0, respectively). After ET cycles with a single blastocyst, a positive pregnancy test was positively and significantly associated with longer computer use (OR = 2.0, CI = 1.1-3.7), while GS detection was significantly more likely in women with longer computer use (OR = 2.1, CI = 1.1-3.8) and tended to be more likely in women with a higher FertiQoL Total scaled treatment score (OR = 1.8, CI = 1.0-3.3). p < 0.05 was considered statistically significant and 0.05 ≤ p <0.01 as tendency. Conclusions: Olive oil may be an important factor in dietary habits. Fertility-specific QOL and smoking cessation guidance for partners are important for infertile couples.


Asunto(s)
Infertilidad , Calidad de Vida , Humanos , Embarazo , Femenino , Estudios Prospectivos , Aceite de Oliva , Fertilidad , Fertilización In Vitro , Infertilidad/terapia , Estilo de Vida
2.
Reprod Sci ; 27(3): 869-876, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32046466

RESUMEN

In endometriosis, M2 macrophages (MΦ) are dominant and promote the development of endometriosis lesions. However, the factor(s) which induces M2 MΦ are unknown. In the present study, we focused on interleukin (IL)-33, known as an alarmin and investigated its expression and its role in endometriosis, especially from the point of the relevance with MΦ. The expression of IL-33 in endometriosis lesions was examined by immunohistochemistry. The cystic fluid of ovarian cysts/tumors was obtained and used to measure IL-33 concentration. Endometriotic stromal cells (ESC) and MΦ derived from patients were used for in vitro experiments. IL-33 was detected in the epithelium and stromal cells of endometriotic lesions. The mean IL-33 concentration in the cystic fluid of endometriomas was significantly higher than that in non-endometriomas (2.2 ng/ml vs. 0.02 ng/ml, P < 0.01). IL-1ß induced IL-33 mRNA expression in ESC via p38 MAPK activation. With IL-33 stimulation, peritoneal MΦ polarized to M2 MΦ and produced IL-1ß mRNA with a 2.2-fold increase, which was negated with soluble ST2, a decoy receptor of IL-33. IL-33, derived from endometriotic lesions, stimulated MΦ to produce IL-1ß, which results in increasing IL-33 production in ESC. This cycle may continue to exacerbate the endometriotic lesions.


Asunto(s)
Endometriosis/metabolismo , Endometriosis/patología , Endometritis/metabolismo , Interleucina-33/metabolismo , Macrófagos Peritoneales/metabolismo , Peritoneo/metabolismo , Adulto , Endometriosis/complicaciones , Endometritis/complicaciones , Femenino , Humanos , Peritoneo/patología , Transducción de Señal
3.
J Obstet Gynaecol Res ; 45(8): 1613-1618, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31183953

RESUMEN

Laparoscopic port site endometriosis is less common in abdominal wall endometriosis, and malignant transformation of abdominal wall endometriosis is rare. We reported a case of mixed endometrioid and clear cell carcinoma arising from port site endometriosis. The patient was a 49-year-old woman with a history of laparoscopic excision of ovarian endometrioma. Physical examination revealed a subcutaneous solid tumor around the laparoscopic surgical scar. Imaging showed a suspicious malignancy. She underwent radical marginal resection of the abdominal wall tumor, flap reconstruction of the abdominal wall, hysterectomy, bilateral salpingo-oophorectomy and omental biopsy. Histological examination revealed mixed endometrioid and clear cell carcinoma. Computed tomography scan showed no evidence of recurrence after six cycles of chemotherapy. This is the first case of malignant transformation from laparoscopic trocar site endometriosis.


Asunto(s)
Neoplasias Abdominales , Adenocarcinoma de Células Claras , Carcinoma Endometrioide , Transformación Celular Neoplásica , Endometriosis , Laparoscopía/efectos adversos , Enfermedades del Ovario , Neoplasias Abdominales/diagnóstico , Neoplasias Abdominales/etiología , Neoplasias Abdominales/cirugía , Adenocarcinoma de Células Claras/diagnóstico , Adenocarcinoma de Células Claras/etiología , Adenocarcinoma de Células Claras/cirugía , Carcinoma Endometrioide/diagnóstico , Carcinoma Endometrioide/etiología , Carcinoma Endometrioide/cirugía , Endometriosis/complicaciones , Endometriosis/diagnóstico , Endometriosis/etiología , Endometriosis/cirugía , Femenino , Humanos , Persona de Mediana Edad , Enfermedades del Ovario/diagnóstico , Enfermedades del Ovario/etiología , Enfermedades del Ovario/cirugía
4.
Am J Reprod Immunol ; 78(1)2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28337819

RESUMEN

PROBLEM: Plasminogen activator inhibitor-1 (PAI-1) is elevated in women with polycystic ovary syndrome (PCOS), but the regulation in granulosa cells (GCs) is unclear. METHOD OF STUDY: PAI-1 expression in PCOS ovaries was investigated immunohistologically. PAI-1 expressions in HGrC1, a human GC cell line, were investigated at mRNA and activity levels. The expressions of TGF-ß and TNF-α in peritoneal fluid mononuclear cells (PFMCs) were measured with quantitative PCR. RESULTS: Little PAI-1 expression is observed in healthy GCs, whereas GCs of PCOS and atretic follicle exhibit distinct expression in vivo. In vitro study using HGrC1 shows that TGF-ß and TNF-α increase PAI-1 mRNA and its activity, and both together exhibit a synergistic effect. The expression of PAI-1 mRNA is suppressed by simvastatin. Moreover, insulin-sensitizing drugs (metformin, pioglitazone, and rosiglitazone) suppress LPS-induced TGF-ß and TNF-α mRNA expression in PFMC. CONCLUSION: Statin and insulin-sensitizing drugs may provide a potential therapy for PCOS via down-regulation of PAI-1 expression in GCs and down-regulation of TGF-ß and TNF-α expression in PFMC, respectively.


Asunto(s)
Células de la Granulosa/efectos de los fármacos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Hipoglucemiantes/farmacología , Leucocitos Mononucleares/efectos de los fármacos , Inhibidor 1 de Activador Plasminogénico/metabolismo , Factor de Crecimiento Transformador beta/genética , Factor de Necrosis Tumoral alfa/genética , Líquido Ascítico/citología , Línea Celular , Femenino , Células de la Granulosa/metabolismo , Humanos , Leucocitos Mononucleares/metabolismo , Lipopolisacáridos , Folículo Ovárico/metabolismo , Inhibidor 1 de Activador Plasminogénico/genética , Síndrome del Ovario Poliquístico/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , ARN Mensajero/metabolismo , Simvastatina/farmacología
5.
Am J Reprod Immunol ; 76(6): 491-498, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27766701

RESUMEN

OBJECTIVE: We investigated α-7 nAchR expression in human peritoneal macrophages and examined whether activation of nAchR might be a new therapy for endometriosis. MATERIALS AND METHODS: Human peritoneal fluid mononuclear cells (PFMC) were stimulated with lipopolysaccharide (LPS) in the presence of α-7 nAChR agonists. In a murine endometriosis model, α-7 nAChR modulators were administered. RESULTS: Human PFMC expressed α-7 nAChR at the mRNA and protein levels. Activation of α-7 nAChR with its agonists led to significant (P<.01) suppression of LPS-induced interleukin (IL) -1ß expression. In a murine endometriosis model, one week after inoculation of endometrium to the peritoneal cavity, α-7 nAChR agonist significantly suppressed the expression of IL-1ß mRNA (P<.01), which was negated when α-7 nAChR antagonist was administered simultaneously. α-7 nAChR agonist significantly suppressed the formation of endometriotic lesions, which was reversed with α-7 nAChR antagonist. CONCLUSION: Activation of nAChR might be a new candidate for treatment of endometriosis.


Asunto(s)
Aconitina/análogos & derivados , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Endometriosis/prevención & control , Macrófagos Peritoneales/efectos de los fármacos , Quinuclidinas/farmacología , ARN Mensajero/inmunología , Receptor Nicotínico de Acetilcolina alfa 7/inmunología , Aconitina/farmacología , Adulto , Animales , Líquido Ascítico/citología , Líquido Ascítico/inmunología , Compuestos Bicíclicos Heterocíclicos con Puentes/antagonistas & inhibidores , Modelos Animales de Enfermedad , Endometriosis/genética , Endometriosis/inmunología , Endometriosis/patología , Endometrio/efectos de los fármacos , Endometrio/inmunología , Endometrio/patología , Femenino , Regulación de la Expresión Génica , Humanos , Interleucina-1beta/antagonistas & inhibidores , Interleucina-1beta/genética , Interleucina-1beta/inmunología , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Activación de Macrófagos/efectos de los fármacos , Macrófagos Peritoneales/inmunología , Macrófagos Peritoneales/patología , Ratones , Nicotina/farmacología , Cultivo Primario de Células , Quinuclidinas/antagonistas & inhibidores , ARN Mensajero/agonistas , ARN Mensajero/antagonistas & inhibidores , ARN Mensajero/genética , Índice de Severidad de la Enfermedad , Transducción de Señal , Receptor Nicotínico de Acetilcolina alfa 7/agonistas , Receptor Nicotínico de Acetilcolina alfa 7/antagonistas & inhibidores , Receptor Nicotínico de Acetilcolina alfa 7/genética
6.
Am J Reprod Immunol ; 72(5): 496-503, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24974860

RESUMEN

PROBLEM: Immune tolerance to endometriotic cells is important to promote endometriosis. Tryptophan 2,3-dioxygenase (TDO) enhances immune tolerance by catabolizing tryptophan to kynurenine. We studied whether interleukin-1ß (IL-1ß), a typical endometriosis-associated cytokine, affects the expression of TDO and the catabolism of tryptophan in endometrioma stromal cells (ESCs). We also studied whether the expression of TDO is involved in IL-1ß-induced secretion of IL-6 and IL-8 in ESCs. METHOD OF STUDY: Nineteen endometriotic patients of reproductive age with normal menstrual cycles were recruited. Primary cultures of ESCs were treated with IL-1ß and TDO siRNA. TDO mRNA was measured using quantitative PCR. TDO protein was measured using Western blotting. Concentrations of kynurenine in condition media were measured using Ehrlich reagent. Concentrations of tryptophan in conditioned media were measured using tryptophan detection kit. Concentrations of IL-6 and IL-8 in conditioned media were measured using ELISA kits. RESULTS: IL-1ß (1 ng/mL) increased the expression of TDO mRNA and TDO protein in ESCs. IL-1ß-treated ESCs increased the production of kynurenine and the effect was inhibited by TDO siRNA. Treatment with the siRNA also decreased IL-1ß-induced secretion of IL-6 and IL-8 from ESCs. CONCLUSION: IL-1ß is suggested to stimulate tryptophan catabolism and production of IL-6 and IL-8 by increasing TDO expression in endometriosis.


Asunto(s)
Endometriosis/inmunología , Endometrio/inmunología , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Interleucina-1beta/farmacología , Triptófano Oxigenasa/inmunología , Adulto , Células Cultivadas , Endometriosis/metabolismo , Endometriosis/patología , Endometrio/metabolismo , Endometrio/patología , Femenino , Regulación Enzimológica de la Expresión Génica/inmunología , Humanos , Interleucina-1beta/inmunología , Interleucina-1beta/metabolismo , Interleucina-6/inmunología , Interleucina-6/metabolismo , Interleucina-8/inmunología , Interleucina-8/metabolismo , Células del Estroma/inmunología , Células del Estroma/metabolismo , Células del Estroma/patología , Triptófano Oxigenasa/biosíntesis
7.
Reprod Sci ; 21(6): 772-7, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24406789

RESUMEN

Bone morphogenetic protein (BMP) cytokine is known to regulate ovulation, as BMP-6 null mice exhibit a decrease in the number of ovulatory follicles without effect on either the morphology or the dynamics of follicular development. In the present study, the role of BMP-6 in ovulatory process was investigated using human granulosa-lutein cells (GCs). Granulosa-lutein cells, obtained from in vitro fertilization patients, were cultured with BMP-6 followed by RNA extraction. The neutrophil-chemotactic activity of the supernatant of cultured GC was investigated. Bone morphogenetic protein 6 significantly increased growth-regulated oncogene α (GRO-α) messenger RNA (mRNA) and protein expression in GC. In the neutrophil-chemotaxis assay, the GC supernatant cultured with BMP-6 attracted more neutrophils than control samples, which was negated with anti-GRO-α neutralizing antibody. Bone morphogenetic protein 6 also suppressed the relative expression of the protease inhibitors, secretory leukocyte peptidase inhibitor, and whey acid protein 14 mRNA in GC. Bone morphogenetic protein 6 might play a role in ovulation by increasing the accumulation of neutrophils in the ovulatory follicle and suppressing the effect of protease inhibitors.


Asunto(s)
Proteína Morfogenética Ósea 6/fisiología , Movimiento Celular/fisiología , Neutrófilos/fisiología , Ovario/citología , Ovario/fisiología , Femenino , Humanos , Premenopausia/fisiología
8.
Reprod Sci ; 21(4): 477-82, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24023033

RESUMEN

The formation of an individual capillary network in the theca cell layer is required for ovarian folliculogenesis. Although vascular endothelial growth factor (VEGF) is critical for this process, the regulation of VEGF has been unclear. In the present study, the relationship between VEGF and intraovarian cytokine, bone morphogenetic protein 7 (BMP-7) was investigated. Granulosa cells (GC), obtained from in vitro fertilization patients, were cultured with BMP-7 followed by RNA extraction. Human umbilical vein endothelial cells (HUVECs) were also cultured with BMP-7 followed by RNA extraction, tube formation assay, or cell count analysis. The BMP-7 stimulated VEGF messenger RNA (mRNA) and protein expression in GC significantly. In HUVEC, BMP-7 increased an approximately 1.8-fold in the cell number and induced the tube formation significantly compared to control. The BMP-7 also induced a 2-fold increase in VEGF receptor mRNA transcript relative abundance in HUVEC. The BMP-7, a theca cell-derived factor, may stimulate endothelial cell to form vasculature in the follicle via 2 distinct mechanisms, induction of VEGF expression in GC and increased sensitivity of endothelial cells to VEGF.


Asunto(s)
Proteína Morfogenética Ósea 7/farmacología , Células de la Granulosa/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Receptores de Factores de Crecimiento Endotelial Vascular/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Células Cultivadas , Relación Dosis-Respuesta a Droga , Femenino , Células de la Granulosa/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Neovascularización Fisiológica/efectos de los fármacos , ARN Mensajero/metabolismo , Receptores de Factores de Crecimiento Endotelial Vascular/genética , Receptores de Factores de Crecimiento Endotelial Vascular/metabolismo , Factores de Tiempo , Regulación hacia Arriba , Factor A de Crecimiento Endotelial Vascular/genética
9.
J Clin Endocrinol Metab ; 98(4): 1583-90, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23450050

RESUMEN

CONTEXT: Endometriosis is a chronic inflammatory disease in which immune response and production of estrogen in endometriotic tissues are involved in the development of the disease. Prostaglandin E2 (PGE2) stimulates aromatase (P450arom) expression in endometrioma stromal cells (ESCs) and increases the production of estrogens. On the other hand, an accumulating amount of evidence suggests that IL-4, a typical Th2 cytokine, plays important roles in the disease. OBJECTIVE: The objective of the investigation was to study the effect of IL-4 on the expression of 3ß-hydroxysteroid dehydrogenase (HSD3B2), a pivotal enzyme for estrogen production, in ESCs. DESIGN, PATIENTS, AND MAIN OUTCOME MEASURES: ESCs were isolated from ovarian endometrioma tissues and cultured with IL-4 and PGE2. CP-690550, a Janus protein tyrosine kinase 3 inhibitor, and HSD3B2 small interfering RNA were added to the culture. Gene expression of HSD3B2 and P450arom was examined by quantitative RT-PCR. Dehydroepiandrosterone (DHEA) was added to the culture, and then the combined enzyme activity of HSD3B2, which converts DHEA to androstenedione, and P450arom, which converts androstenedione to estrone, was examined by measuring estrone concentration in the supernatants with a specific enzyme immunoassay. RESULTS: IL-4 increased the expression of HSD3B2 mRNA in a dose-dependent manner. CP-650550 inhibited the IL-4-induced increase in HSD3B2 mRNA expression. PGE2 also increased the expression of HSD3B2 mRNA, and the combination of IL-4 and PGE2 synergistically increased the expression of HSD3B2 mRNA. IL-4 had no effect on the expression of P450arom mRNA, whereas PGE2 increased the expression of P450arom mRNA. Although PGE2 alone increased the production of estrone from DHEA, the combination of IL-4 and PGE2 significantly augmented the production of estrone from DHEA. The enhanced production of estrone by the combination of IL-4 and PGE2 was inhibited by CP-690550 and HSD3B2 small interfering RNA. CONCLUSIONS: IL-4 in combination with PGE2 may enhance estrogen production in endometriotic tissues, implying an elaborate mechanism that Th2 immune response augments inflammation-dependent progression of the disease.


Asunto(s)
Dinoprostona/farmacología , Endometriosis/genética , Interleucina-4/farmacología , Enfermedades del Ovario/genética , Progesterona Reductasa/genética , Células del Estroma/efectos de los fármacos , Células Cultivadas , Sinergismo Farmacológico , Endometriosis/enzimología , Endometriosis/metabolismo , Endometriosis/patología , Estrona/metabolismo , Femenino , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Humanos , Modelos Biológicos , Enfermedades del Ovario/enzimología , Enfermedades del Ovario/metabolismo , Enfermedades del Ovario/patología , Embarazo , Progesterona Reductasa/antagonistas & inhibidores , Progesterona Reductasa/metabolismo , ARN Interferente Pequeño/farmacología , Células del Estroma/enzimología , Células del Estroma/metabolismo , Células del Estroma/patología , Regulación hacia Arriba/efectos de los fármacos
10.
Reprod Sci ; 20(6): 675-9, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23171678

RESUMEN

The aim of this study is to examine the regulation of follistatin, an activin-binding protein, in endometriosis. Endometrioma stromal cells (EoSCs) were obtained from 9 patients undergoing laparoscopy of the ovarian endometrioma. In cultured EoSCs, interleukin 1ß (IL-1ß) and tumor necrosis factor-α (TNF-α), which could induce activin-A, also induced follistatin messenger RNA (mRNA) and protein. The cystic fluid of endometrioma from 8 patients was obtained to measure the concentration of activin-A and follistatin by enzyme-linked immunosorbent assay (ELISA). Also, activin activity in the fluid was examined by erythroid differentiation assay using mouse erythroleukemia F5-5.fl cells. In the cystic fluid of endometrioma, the mean values of activin-A and follistatin concentration were 36.8 ng/mL and 4.0 ng/mL, respectively. In a bioassay, all 8 samples exhibited activin activity, which was equivalent to recombinant activin-A activity of 12.8 ± 1.4 ng/mL. Although follistatin was present in the cystic fluid of endometrioma, the activity of activin, which is an exacerbation factor of endometriosis, was predominant in vivo.


Asunto(s)
Endometriosis/metabolismo , Folistatina/metabolismo , Interleucina-1beta/metabolismo , Células del Estroma/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Activinas/metabolismo , Animales , Línea Celular , Ensayo de Inmunoadsorción Enzimática , Femenino , Folistatina/genética , Humanos , Ratones , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Proteínas Recombinantes/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Regulación hacia Arriba
11.
Am J Reprod Immunol ; 68(6): 491-8, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22935039

RESUMEN

PROBLEM: The aim of this study is to evaluate the expression and regulation of proprotein convertase subtilisin/kexin (PCSK) 6, which is known to be an important factor in the production of bone morphogenetic protein (BMP) cytokines in human ovary. METHOD OF STUDY: The localization of PCSK 6 protein in normal human ovaries was examined by immunohistochemistry. Human granulosa cells (GC), obtained from 34 patients undergoing ovarian stimulation for in vitro fertilization, were cultured with BMP-2, BMP-6, BMP-7, BMP-15, growth differentiation factor (GDF)-9, and activin-A with or without FSH. PCSK 6 mRNA expression level was evaluated by quantitative real-time reverse transcription and polymerase chain reaction (RT-PCR). RESULTS: An immunohistochemistry study revealed that GC expressed PCSK 6 throughout follicular development, beginning in the primary follicle stage, while oocytes expressed PCSK 6 from the primordial follicle stage onwards. An in vitro study demonstrated that BMP-2, BMP-6, BMP-7, and BMP-15, not activin-A and GDF-9, decreased PCSK 6 gene expression in human GC. FSH induced PCSK 6 mRNA in the presence of activin-A or GDF-9. GDF-3, which is an inhibitor of BMP cytokines, also induced PCSK 6 mRNA expression. CONCLUSIONS: PCSK 6, which is a critical factor to produce BMP cytokines, was suppressed with BMP stimulation in human GC, suggesting the presence of a negative feedback system in the follicular development process.


Asunto(s)
Activinas/farmacología , Proteínas Morfogenéticas Óseas/farmacología , Factor 9 de Diferenciación de Crecimiento/farmacología , Ovario/enzimología , Proproteína Convertasas/metabolismo , Serina Endopeptidasas/metabolismo , Adulto , Proteínas Morfogenéticas Óseas/biosíntesis , Células Cultivadas , Femenino , Fase Folicular , Células de la Granulosa/enzimología , Humanos , Inmunohistoquímica , Folículo Ovárico/enzimología , Folículo Ovárico/crecimiento & desarrollo , Proproteína Convertasas/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Serina Endopeptidasas/genética
12.
Fertil Steril ; 97(4): 979-83, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22305102

RESUMEN

OBJECTIVE: To examine the relevance of growth differentiation factor 3 (GDF-3) and bone morphogenetic protein (BMP) cytokines in human ovary. DESIGN: Molecular studies. SETTING: Research laboratory. PATIENT(S): Eight women undergoing salpingo-oophorectomy and 30 women undergoing ovarian stimulation for in vitro fertilization. INTERVENTION(S): Localizing GDF-3 protein in human ovaries; granulosa cells (GC) cultured with GDF-3, BMP-6, or BMP-7 followed by RNA extraction. MAIN OUTCOME MEASURE(S): The localization of GDF-3 protein in normal human ovaries via immunohistochemical analysis, GDF-3 messenger RNA (mRNA) expression evaluation via quantitative real-time reverse transcription and polymerase chain reaction (RT-PCR), and evaluation of the effect of GDF-3 on leuteinizing hormone (LH) receptor mRNA expression via quantitative real-time RT-PCR. RESULT(S): In the ovary, BMP cytokines, of the transforming growth factor beta (TGF-ß) superfamily, are known as a luteinization inhibitor by suppressing LH receptor expression in GC. Growth differentiation factor 3, a TGF-ß superfamily cytokine, is recognized as an inhibitor of BMP cytokines in other cells. Immunohistochemical analysis showed that GDF-3 was strongly detected in the GC of antral follicles. An in vitro assay revealed that BMP-6 or BMP-7 induced GDF-3 mRNA in GC. Also, GDF-3 increased LH receptor mRNA expression and inhibited the effect of BMP-7, which suppressed the LH receptor mRNA expression in GC. CONCLUSION(S): GDF-3, induced with BMP-6 and BMP-7, might play a role in folliculogenesis by inhibiting the effect of BMP cytokines.


Asunto(s)
Proteína Morfogenética Ósea 6/metabolismo , Proteína Morfogenética Ósea 7/metabolismo , Células de la Granulosa/metabolismo , Factor 3 de Diferenciación de Crecimiento/metabolismo , Hormona Luteinizante/genética , ARN Mensajero/metabolismo , Adulto , Células Cultivadas , Femenino , Humanos , Inmunohistoquímica , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores de HL/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Regulación hacia Arriba
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