Journal of the Society for Gynecologic Investigation最新文献

Objective: To compare matrix metalloproteinase (MMP)-8 and MMP-9 levels in the vaginal secretions of pregnant women with or without asymptomatic bacterial vaginosis (BV).

Methods: In this study, vaginal levels and molecular forms of MMP-8 and MMP-9 were studied in 36 pregnant women between 28 and 34 weeks of gestation with asymptomatic BV and 41 pregnant women, matched for gestational age, without BV.

Results: Vaginal MMP-8 concentrations were significantly higher (P = .023) in BV-positive women. There was no significant difference in MMP-9 levels between healthy pregnant controls and BV-positive pregnant women. The presence of MMP-8 was confirmed by a 38-kd band on Western blots.

Conclusions: Our findings show that BV is associated with increased levels of MMP-8 in vaginal fluid. Increased production of collagen-degrading enzymes such as MMP-8 is a possible cause of spontaneous preterm delivery in pregnant women with asymptomatic BV.

Objectives: Maternal physiology at high altitude could be considered to resemble an intermediate state between preeclampsia and normal pregnancy. The objective of the current study was to determine if cell adhesion molecules, known to be increased in preeclampsia, are increased with chronic maternal and placental hypoxia (due to high-altitude residence) in the absence of preeclampsia.

Methods: Serum was collected from women residing at 3100 m or 1600 m in the three trimesters of pregnancy and postpartum. Vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and intercellular adhesion molecule-1 (ICAM-1) were measured by enzyme-linked immunosorbent assay (ELISA).

Results: General linear model (GLM) repeated measures analysis of VCAM-1, E-selectin, and ICAM-1 data showed there were no statistically significant effects of gestation within either the high- or moderate-altitude groups or between the different altitudes.

Conclusion: The increase in cell adhesion molecules reported in preeclampsia is not present in pregnant women at high altitude, suggesting that maternal systemic hypoxia is not responsible for this pathway of endothelial cell activation in preeclampsia.

Objective: This study tested the hypothesis that the endothelin (ET)/ET receptor (ETR) system in biologic fluids and in the human placenta is altered in delayed miscarriages as compared to apparently normal early pregnancies (reference group).

Methods: Immunoreactive ET (irET) concentrations were measured in plasma, urine, and cervical smears from 57 pregnant women in the weeks 6 to 14 of gestation (46 delayed miscarriages, 11 references) with radioimmunoassay (RIA). ET-1, ETR-A, and ETR-B mRNA, and ETR protein expression were measured in placental tissue of 45 early pregnancies (31 delayed miscarriages, 14 references) using semiquantitative reverse-transcription polymerase chain reaction (RT-PCR) and immunoblotting, respectively.

Results: irET levels in plasma, urine, and cervical smears did not differ between groups. Two prevailing ETR-A and ETR-B proteins were found at 45 and 55 kd, and were distributed similarly in delayed miscarriages and references. ETR-A protein and mRNA levels were 54% (P = .009) and threefold (P = .021) higher, respectively, in delayed miscarriages versus references. There was no difference in placental ETR-B and ET-1 mRNA levels between groups.

Conclusion: Neither irET nor ET-1 mRNA levels differ between delayed miscarriages and normal early pregnancies. Pregnancies at risk for miscarriage cannot be identified by measurement of ET in plasma, urine, or cervical smears. Within the ET/ETR system, ETR-A is selectively up-regulated in placental tissue of delayed miscarriages as compared to normal pregnancies. ETR protein processing is similar in both groups.

Objective: The purpose of the current study was to determine if neutrophils infiltrate maternal systemic vascular tissue at the time of term labor.

Methods: Subcutaneous fat biopsies were obtained at cesarean delivery or abdominal surgery from laboring women (n = 5), non-laboring women (n = 5), and normal non-pregnant women (n = 5). Immunohistochemical staining was performed for CD66b, a neutrophil antigen, and intercellular adhesion molecule-1 (ICAM-1; CD54), an endothelial cell adhesion molecule for neutrophils. Vessels (10 to 200 microm) were analyzed for intensity of staining and percentage of vessels with staining.

Results: CD66b staining intensity was significantly greater for laboring women at term than for non-laboring women at term or for normal non-pregnant women (1.3 +/- 0.3 versus 0.2 +/- 0.1 versus 0.2 +/- 0.1, respectively, P < .01). Laboring women had significantly more vessels with staining for CD66b (79 +/- 4 versus 24 +/- 8 versus 19 +/- 6%, P < .001), more vessels with neutrophils adhered and flattened to endothelium (67 +/- 3 versus 16 +/- 7 versus 12 +/- 4%, P < .001), more vessels with neutrophils in the intima (30 +/- 6 versus 5 +/- 2 versus 2 +/- 1%, P < .05), and a greater number of neutrophils per vessel (5.4 +/- 1.1 versus 1.7 +/- 0.5 versus 1.2 +/- 0.3, P < .01) as compared to non-laboring or normal non-pregnant women. ICAM-1 staining was present in the endothelium of all groups, with no difference in staining intensity or percent of vessels stained. Between 86% to 96% of vessels stained for ICAM-1. Laboring patients had numerous leukocytes stained for ICAM-1 in their vessels.

Conclusion: This study demonstrates that neutrophils infiltrate maternal systemic vascular tissue at the time of term labor. Neutrophils were flattened and adhered to endothelium and infiltrated into the intimal space.

Free radicals are highly reactive molecules produced in the cell either as part of, or as end-products of, biochemical reactions that have crucial roles in the homeostasis of the organism. Thus, excess production or impaired elimination of free radicals leads to increased oxidative stress, which has been implicated in the development of several different disease states, including hypoxia-reperfusion injury, cancer, and aging. Peritoneal adhesions and endometriosis are relatively commonly identified in women, and are known to be associated with infertility without clearly understood pathophysiology. The prevention and treatment strategies of these conditions, both of which have tremendous propensity to recur, have not been completely established. The development of both disorders has been shown to be closely related to the presence of increased oxidative stress in the tissues. In this article, we review this relationship with reference to the mechanistic steps involved and their regulation. As our knowledge of both conditions expands, we believe there will be opportunities for specific steps to intervention in free radical metabolism to reduce and/or prevent further development of endometriosis and adhesions.

Objective: To assess the effects of prolonged mild hypoxemia on fetal brain electrocorticogram (ECoG) in late gestation.

Study design: Fetal and maternal catheters were placed under general anesthesia and animals allocated at random to receive intratracheal maternal administration of either nitrogen (n = 8) or compressed air (n = 8). Five days after surgery (125 days' gestational age), nitrogen infusion was adjusted to reduce fetal brachial artery PO2 by 25%. The targeted decrease in fetal oxygenation was maintained for 5 days while fetal ECoG activity and fetal and maternal cardiovascular variables were continuously recorded. Data are presented as mean +/- SEM and were analyzed by two-way analysis of variance (ANOVA) or two-sample t test.

Results: Nitrogen infusion decreased fetal Po2 by 26% (20.5 +/- 1.7 versus 14.3 +/- 0.8) without changing fetal PCO2 or pH. Mild fetal hypoxemia was associated with fetal tachycardia and increased fetal blood pressure (P < .05). Fetal ECoG in hypoxic fetuses showed a significant decrease in the time spent in high voltage (HV) (P < .05) and an increase in the time spent in low voltage (LV) and in the number of low voltage events (P < .05). Also, a significant decrease in the proportion of 1-4 Hz and an increase in the proportion of 13-20 Hz frequencies was observed in LV events without a significant change in the frequency profile of HV events (P < .05).

Conclusion: Prolonged mild hypoxemia significantly altered fetal homeostasis as reflected by the sustained tachycardia and increased blood pressure. Fetal ECoG activity was affected significantly in a qualitatively and quantitative manner by mild prolonged hypoxemia.

Objectives: The current research was conducted to determine whether hyperpolarization-activated cyclic nucleotide-gated (HCN1-4) channels are expressed in gonadotropin-releasing hormone (GnRH) neurons in the female rat hypothalamus and immortalized GnRH neurons (GT1-7 cells).

Methods: Double-label fluorescence immunohistochemistry was used to colocalize HCN1-4 channels and GnRH in GnRH neurons in the female rat hypothalamus. Reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting, and immunocytochemistry were used to analyze HCN channel gene expression in GT1-7 cells.

Results: Double-label fluorescence immunohistochemistry showed that 43% of hypothalamic GnRH neurons immunostained for HCN2 and 90% of GnRH neurons immunostained for HCN3. RT-PCR and Western blot showed expression of all four HCN channel subunits in GT1-7 cells. Double-label immunocytochemistry showed cytoplasmic immunostaining of HCN2 and HCN3 in GT1-7 cells.

Conclusions: This study demonstrates for the first time that HCN channels are expressed in GnRH neurons in the rat hypothalamus and GT1-7 cells. Our research supports the hypothesis that HCN channels may be involved in electrical bursting activity and pulsatile GnRH secretion in endogenous GnRH neurons and GT1-7 cells.

Background: The age-related depletion of the resting follicle (RF) stock occurs as a result of two processes: atresia and entry in growth phase. Due to difficulties in obtaining sufficient numbers of RFs for study, little is known about the apoptotic mechanisms for RF atresia. The present study was designed to investigate the effects of oxidative stress on the apoptosis of RF oocytes.

Methods: RFs isolated from human adult ovaries were cultured in vitro, treated with H2O2 at various concentrations (50 microM, 100 microM, 1.0 mM) for 1 hour, and observed for up to 48 hours. The oxidant-induced apoptosis of oocytes were observed by detection of DNA fragments, mitochondria membrane potential (MMP), and cytochrome c release.

Results: Based on nuclear morphology and TUNEL (terminal deoxynucleotidyl transferase-mediated dDTP nick end-labeling), oocyte apoptosis was observed in the RFs treated with 50 microM H2O2 with rates of 35% and 43% at 24 and 48 h after treatment, respectively. But intensive oxidative stress (1 mM H2O2) caused mainly necrosis as measured by quantifying propidium iodide (PI)-positive oocytes (44% within 12 hours), with lower level of apoptosis (17%) being observed at 24 hours after treatment. RFs treated with 100 microM H2O2 showed both apoptosis with the similar rate observed at 50microM and necrosis (13% PI-positive oocytes). Although pre-incubation with cyclosporine A (CsA) could effectively prevent oxidant-induced MMP collapse, but failed to suppress apoptosis of oocytes in RFs.

Conclusions: Oocytes of RFs in adult ovaries retain their ability to undergo apoptosis under oxidative stress, which is both dose- and time-dependent.

Objectives: Tibolone (Tib) exhibits progestagenic activities in addition to its tissue-specific estrogenic activities. The purpose of the current study was to determine the progestagenic actions of Tib and its metabolites using target genes known to be regulated by progestins in human endometrial glandular and stromal cells.

Methods: Human endometrial glandular and stromal cells were isolated from endometrial tissue fragments and separately incubated with Tib and its metabolites. Real-time polymerase chain reaction (PCR) was used to determine the mRNA content of 17betahydroxy steroid dehydrogenase (17betaHSD, type 2) and sulfotransferase (SULT1E1) in endometrial glandular cells, and prolactin (PRL) and insulin-like growth factor binding protein-1 (IGFBP1) in endometrial stromal cells.

Results: In glandular cells, Tib and Delta4-tibolone (Delta4Tib) significantly increased the content of 17betaHSD and SULT1E1 mRNA. In stromal cells, Tib and Delta4Tib increased PRL mRNA ( approximately 30% of the capacity compared to progesterone) and had little effect on IGFBP1 mRNA. Anti-progestin, RU486, reversed the induction of SULT1E1 and PRL by progesterone or Tib. Also, the two 3 hydroxyl tobolone metabolites, especially 3betaOHTib, showed some progestagenic effects.

Conclusions: The data showed that Tib and Delta4Tib exhibited clear progestagenic effects in endometrial glandular cells by inducing 17betaHSD and SULT1E1, while in stromal cells the response was weaker in the induction of PRL and had little effect on IGFBP1. In addition, the 3betaOHTib metabolite expressed progestagenic activity. These disparate effects in two types of cells may be beneficial for maintaining endometrial cells in a quiescent state.