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Biomedical subjects

Thomas Strowitzki

Publications and source records attributed to Thomas Strowitzki.

At least 19 recordsLinked to original sources

Expression of syndecans, cell-cell interaction regulating heparan sulfate proteoglycans, within the human endometrium and their regulation throughout the menstrual cycle.

OBJECTIVE: To evaluate the expression of syndecan-1, -2, -3, and -4 in different phases of eutopic endometrium of normal cycling women. DESIGN: Prospective observational study. SETTING: University-based research center for reproductive medicine. PATIENT(S): Twenty-nine healthy ovulatory volunteers. INTERVENTION(S): mRNA and protein expression of syndecan-1 to -4 in human endometrium. MAIN OUTCOME MEASURE(S): Real-time polymerase chain reaction of syndecan members and further characterization of mRNA expression of syndecan-1 and -4 with multiprobe RNase protection assays of epithelial and stromal cells after purification with antibody-coated magnetic beads. For confirmation of results, protein expression and localization using immunohistochemistry for syndecan-1 and -4 was performed. RESULT(S): All syndecans were expressed within human endometrium. Syndecan-1 and -4 proved to be significantly upregulated in whole endometrium during the secretory phase (2.73-fold and 2.85-fold, respectively). Using multiprobe RNase protection assays, a significant upregulation of mRNA was noted in epithelial cells during the secretory phase for both syndecan-1 and -4 (7.46-fold and 2.52-fold, respectively) and confirmed by immunohistochemistry. CONCLUSION(S): Cycle-dependent expression of syndecan-1 and -4 suggests that these adhesion proteins are involved in the regulation of the cycling endometrium.

Adult↗

Gene expression profiling of human endometrial-trophoblast interaction in a coculture model.

Investigating the interaction of human endometrium and trophoblast during implantation is difficult in vitro and impossible in vivo. This study was designed to analyze the effect of trophoblast on endometrial stromal cells during implantation by comprehensive gene profiling. An in vitro coculture system of endometrial stromal cells with first-trimester trophoblast explants was established. Trophoblast and endometrial stromal cells were separated after 24 h. Gene expression of endometrial stromal cells after coculture was compared with the gene expression of endometrial stromal cells cultured alone by microarray analysis. We confirmed the expression of distinct genes using real-time PCR. Genes up-regulated included those for inflammatory response, immune response, and chemotaxis (pentraxin-related gene 3, chemokine ligands, IL-8, IL-1 receptors, IL-18 receptor, IL-15, IL-15 receptor, TNF-alpha-induced protein 6, and IL-6 signal transducer), regulators of cell growth (IGF-binding proteins 1 and 2) and signal transduction. Also up-regulated were genes for growth and development, glucose metabolism, and lipid metabolism: DKK-1, WISP, IGF-II, hydroxysteroid 11beta-dehydrogenase 1, hydroxyprostaglandin dehydrogenase 15, prostaglandin E synthase, prostaglandin F receptor, aldehyde dehydrogenase 1 family, member A3 and phosphatidic acid phosphatase type 2B. Other genes included genes for cell-cell signaling (pre-B-cell colony-enhancing factor 1), proteolysis, calcium ion binding, regulation of transcription, and others. Down-regulated genes included genes for proteolysis (MMP-11 and mitochondrial intermediate peptidase), genes for cell death (caspase 6, death-associated protein kinase 1, and histone deacetylase 5), transcription factors (sex determining region Y-box 4, dachshund homolog 1, ets variant gene 1, and zinc finger protein 84 and 435), and genes for humoral immune response (CD24 antigen). Trophoblast has a significant impact on endometrial stromal cell gene expression. Some of the genes regulated by trophoblast in endometrial stromal cells are already known to be regulated by progesterone and show the endocrine function of trophoblast during pregnancy. Others are genes so far unknown to play a role in endometrial-trophoblast interaction and open a wide field of investigation.

Adult↗

The human endometrium as a fertility-determining factor.

Intensive research work has been performed to better understand the regulation of the endometrium and its clinical implications to improve implantation. Although many proteins and molecules may influence endometrial development, their co-ordinated contribution to the implantation process is still poorly understood and a translation into clinical use has not sufficiently been performed. Clinical evaluation of the endometrium by ultrasound and other techniques, like endometrial biopsy and analysis of uterine secretions, has been intensively studied and therapeutic options to improve endometrial function have been suggested and tested. Systemic treatment with heparin, aspirin or corticosteroids did not result in improved implantation rates. Gene therapy and cervical treatment, e.g. with seminal plasma, are still in the phase of clinical research. Therefore, this review focuses on different aspects of endometrial research, which all contribute to the diagnosis, evaluation and therapy of endometrial function and dysfunction. First, the endometrial development towards a receptive milieu is described. Second, the actual clinical evaluation of endometrial receptivity, possible therapeutic strategies and in particular, the evaluation of endometrial function in the non-natural situation of hormonal stimulation is critically evaluated. In conclusion, the endometrium shall be considered as an important fertility-determining factor and therapeutic options should be developed in near future.

Animals↗

Luteal-phase inhibin A and follicular-phase inhibin B levels are not characteristic of patients with an elevated LH-to-FSH ratio.

PURPOSE: To test whether serum inhibin levels are related to differences in gonadotropin concentrations between patients with an elevated LH-to-FSH ratio (ELF patients) and controls. METHODS: 32 ELF patients were matched with controls by age, body mass index (BMI), and cycle length. RESULTS: No statistically significant difference was found in follicular-phase inhibin B levels or midluteal inhibin A levels between cases and controls. Significant negative correlation was observed between follicular-phase inhibin B concentrations and BMI in ELF patients but not among controls. LH and FSH were positively related to inhibin B levels in ELF patients. Midluteal inhibin A correlated with sex hormone-binding globulin in controls but not in ELF patients. CONCLUSIONS: Neither follicular-phase inhibin B levels nor midluteal inhibin A levels are characteristic of patients with an elevated LH-to-FSH ratio. Opposite correlations with LH and BMI suggest dysregulation of inhibin secretion rather than dimeric inhibins having a central role to the endocrinological imbalance observed in polycystic ovary syndrome.

Adult↗

[Complementary and alternative therapies for climacteric symptoms].

OBJECTIVE: Review on complementary and alternative therapies for climacteric symptoms. METHODS: Search for publications about complementary or alternative treatments for climacteric symptoms based on Cochrane Library and Medline (1966-2006) including the references from the identified clinical trials and reviews. RESULTS: Cimicifuga may influence climacteric symptoms, especially hot flushes. Results for phytoestrogens, hop and Salvia seem promising but are less convincing. St. John's wort is an option for the treatment of moderate depressive symptoms. Phytoestrogens seem to have some potential for the prevention of osteoporosis and cardiovascular diseases. Results for the influence of lifestyle on hot flushes are conflicting, but interventions have demonstrated their use for the prevention of osteoporosis and cardiovascular diseases. CONCLUSIONS: Lifestyle modifications, Cimicifuga and phytoestrogens may relieve climacteric symptoms. Phytoestrogens and Cimicifuga should not be given to breast cancer survivors.

Acupuncture↗

Galectin-9: a new endometrial epithelial marker for the mid- and late-secretory and decidual phases in humans.

CONTEXT: The galectin family has been reported to play a role in the regulation of cell growth, cell adhesion, apoptosis, inflammation, and immunomodulation, all of which are important for endometrial function, as well as implantation. OBJECTIVE: The objective of the study was to investigate the expression and regulation of galectin-9, a beta-galactoside-binding lectin in the human endometrium. DESIGN: Galectin-9 mRNA and protein were analyzed in dated endometrial biopsies throughout the menstrual cycle and in human early-pregnancy decidua, as well as in the different endometrial cell compartments. Regulation of galectin-9 by estradiol, progesterone, epidermal growth factor, and interferon-gamma in endometrial epithelial cells in vitro was studied. RESULTS: Galectin-9 mRNA analyzed by RNase protection assay is expressed in the human endometrium, specifically in the human endometrial epithelial cells but not in stromal or immune cells. It is expressed at very low concentrations during the proliferative phase and the early-secretory phase and shows a sharp and significant increase in the mid- and late-secretory phases, the window of implantation, as well as in the decidua. Accordingly, galectin-9 protein is also exclusively increased in human endometrial epithelial cells during the mid- and late-secretory phases and in the decidua, however, not in endometrial stromal cells or decidualized cells in vivo or in vitro. A regulation in vitro by estradiol, progesterone, epidermal growth factor, and interferon-gamma could not be detected. CONCLUSIONS: Based on these findings and on the functional studies of other galectins, we suggest galectin-9 as a novel endometrial marker for the mid- and late-secretory and decidual phases.

Adult↗

Use of serum inhibin B levels at the start of ovarian stimulation and at oocyte pickup in the prediction of assisted reproduction treatment outcome.

OBJECTIVE: To assess whether serum inhibin B levels before gonadotropin administration and at oocyte pickup (OPU) are associated with pregnancy. DESIGN: Retrospective case-control study. SETTING: University-based IVF program. PATIENT(S): Fifty-five IVF pregnancies and 55 control cycles matched by age, type of infertility, E(2) at ovulation induction, number of oocytes retrieved, and number of embryos replaced. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Association between serum inhibin B at stimulation day 1 (SD1) and OPU and pregnancy; correlation between inhibin B with clinical and endocrine parameters; predictive accuracy of inhibin B measurements at OPU. RESULT(S): Inhibin B on SD1 was similar between pregnant and nonpregnant subjects, whereas it was significantly higher at OPU in pregnant cycles, but did not allow differentiation between pregnancy outcomes. Inhibin B on SD1 was positively correlated with same-day E(2) in both groups and inversely with age in pregnant cycles. In both groups, inhibin B at OPU correlated positively with number of oocytes collected and with E(2) at ovulation induction. CONCLUSION(S): Higher inhibin B concentrations at OPU are predictive of clinical pregnancy, independently of age, peak E(2), number of oocytes retrieved and number of embryos replaced. Inhibin B on stimulation day 1 did not prove to be a useful predictor.

Adult↗

Serum CA-125 levels in the second week after embryo transfer predict clinical pregnancy.

OBJECTIVE: To correlate CA-125 concentrations in serum samples collected for routine hCG measurements 11 +/- 2 days after embryo transfer in relation to pregnancy and its outcome. DESIGN: Retrospective study. SETTING: University-based in vitro fertilization (IVF) program. PATIENT(S): One hundred and eighty-two consecutive pregnancies conceived after IVF or intracytoplasmic sperm injection, and 41 control cycles without pregnancy from the same patients. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Analysis of correlation between CA-125 concentrations and hCG and inhibin A levels. Predictive accuracy of these markers was compared by receiver-operating characteristic (ROC) analysis. RESULT(S): The CA-125 levels were statistically significantly higher in pregnant than in nonpregnant patients. Within pregnant cycles, CA-125 concentrations correlated positively with levels of hCG and inhibin A. The CA-125 levels were statistically significantly lower in preclinical abortions than in clinical pregnancies. No statistically significant difference was observed between early pregnancy losses and ongoing pregnancies or singleton and multiple pregnancies, respectively. The predictive accuracy of CA-125 measurements was statistically significantly lower than that achieved with hCG or inhibin A. CONCLUSION(S): Although CA-125 levels seem to be predictive of clinical pregnancy, they are not predictive of its outcome. Higher CA-125 concentrations may reflect higher endometrial receptivity but do not predict the number or viability of implanted embryos.

Adult↗

Serum CA-125 and inhibin B levels in the prediction of ovarian response to gonadotropin stimulation in in vitro fertilization cycles.

There is much controversy about the relationship between serum CA-125 levels during in vitro fertilization (IVF) cycles and ovarian function. To evaluate the prognostic value of serum CA-125 and inhibin B measurements in predicting ovarian response to gonadotropin stimulation, we compared the CA-125 and inhibin B levels of poor and normal responders on the first day of ovarian stimulation, on the day of ovulation induction (OI) and at oocyte pick-up. Sixteen patients with poor ovarian response (3 oocytes, serum estradiol (E2) 900 pg/ml at OI) in IVF/intracytoplasmic sperm injection cycles were matched with normal responders (6 oocytes, E2 1800 pg/ml) by age, spontaneous cycle day-3 follicle-stimulating hormone level and cause of infertility. Inhibin B concentrations were significantly lower at all three time points in poor responders, but CA-125 levels were not. No statistically significant correlation was found between CA-125 levels and any of the clinical or laboratory parameters examined. Thus, CA-125 measurements during stimulation are not useful in predicting or identifying poor ovarian response to gonadotropin stimulation in IVF cycles. The lack of difference in CA-125 concentrations between poor and normal responders and lack of correlation with E2 or inhibin B levels suggest that ovarian steroidogenesis and other granulosa cell functions do not influence the production of CA-125. Inhibin B, however, seems to predict ovarian response as early as at the start of stimulation.

Animals↗

Intraoperative venous blood sampling to localize a small androgen-producing ovarian tumor.

BACKGROUND: Among other causes of virilization, ovarian tumors can be the cause of excessive androgen production. We report the case of a Leydig cell tumor of the ovary where diagnostic attempts to localize the source of hyperandrogenism preoperatively failed owing to relatively small tumor size. CASE: A 36-year-old woman presented with clinical signs of severe virilization including progressive balding, increased hirsutism, secondary amenorrhea and enlargement of the clitoris. Extensive work-up included endocrinological tests, pelvic ultrasound, magnetic resonance imaging, chromosomal analysis, norcholesterol scintigraphy and selective venous sampling, without direct localization of the source of hyperandrogenism. Persistently high plasma testosterone prompted an explorative laparotomy. Intraoperative selective blood sampling of the ovarian veins and palpation gave evidence of a right ovarian tumor, which was then removed. Histological examination revealed the presence of a pure Leydig cell tumor. CONCLUSION: Exploratory laparotomy with intraoperative selective blood sampling of the ovarian veins might be a useful approach in patients without accurate preoperative localization of androgen-producing tumors of the ovaries.

Adrenocorticotropic Hormone↗

Use of serum inhibin A and human chorionic gonadotropin measurements to predict the outcome of in vitro fertilization pregnancies.

OBJECTIVE: To assess the clinical value of maternal serum inhibin A measurements in early pregnancy in the prediction of outcome of IVF pregnancies and to compare the predictive accuracy of inhibin A concentrations with serum hCG concentrations. DESIGN: Retrospective study.University-based IVF program. PATIENT(S): One hundred fifty IVF pregnancies of 150 couples were studied during a 4-year period. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The association between pregnancy outcome and age, number of collected oocytes, number of transferred embryos, and serum hCG and inhibin A concentrations in early pregnancy was studied with logistic regression. Predictive accuracy of inhibin A and hCG concentrations was calculated by receiver-operating characteristic (ROC) analysis. RESULT(S): Lower serum concentrations of inhibin A and hCG were associated with increased odds for preclinical abortion and early pregnancy loss, whereas higher inhibin A and hCG concentrations were observed in multiple ongoing pregnancies. Inhibin A measurements were superior to hCG in the prediction of preclinical abortions; no significant difference was observed between the predictive value of hCG, inhibin A, or their combination in differentiating between ongoing pregnancies and early pregnancy losses. The discriminative potential of inhibin A for prognosticating multiple ongoing pregnancies was lower than that of hCG. CONCLUSION(S): Although serum inhibin A concentrations are more accurate than hCG levels for predicting preclinical abortion after IVF, they had no advantage in forecasting ongoing or multiple ongoing pregnancies, suggesting that routine assessment of serum inhibin A concentrations during follow-up of IVF pregnancies is unjustified.

Abortion, Spontaneous↗

Osteopontin is up-regulated in human decidual stromal cells.

OBJECTIVE: To analyze expression and regulation of osteopontin in human stromal endometrial and decidual cells. DESIGN: Study by immunohistochemistry, RNase protection assay, and in vitro study. SETTING: Academic research unit. PATIENT(S): Twenty-five fertile women. INTERVENTION(S): Expression of osteopontin mRNA and protein was analyzed by RNase protection assay (RPA) and immunohistochemistry in secretory endometrium and decidua. Regulation of osteopontin expression in endometrial epithelial cell and stromal cells was analyzed by incubation with 17beta-estrogen, progesterone, IL-1beta, IL-6, and LIF and by incubation with cell culture supernatants of decidual natural killer cells. Furthermore, osteopontin expression was studied in stromal cells, decidualized in vitro. MAIN OUTCOME MEASURE(S): mRNA and protein expression and regulation of endometrial stromal osteopontin. RESULT(S): Osteopontin mRNA and protein are expressed at increasing concentrations in human secretory endometrium and in decidua. High concentrations in total decidua were due to high osteopontin concentrations in decidualized stromal cells. Osteopontin mRNA and protein expression was not regulated by incubation of endometrial epithelial and stromal cells with steroids, cytokines, and natural killer cell supernatant for 6 and 24 hours. In contrast, decidualization of stromal cells for 7, 14, and 21 days resulted in significant up-regulation of osteopontin mRNA and protein. CONCLUSION(S): Osteopontin is expressed at high concentrations in secretory endometrium in epithelial cells and in decidua in stromal cells. Decidual stromal expression of osteopontin is up-regulated by decidualization.

Cells, Cultured↗

Oral contraception does not alter single dose saquinavir pharmacokinetics in women.

AIMS: Women experience more adverse drug reactions (ADR) to antiretroviral therapy than men. This may be attributed to higher plasma concentrations of protease inhibitors due to pharmacokinetic interactions with hormonal preparations. Thus, in the present study we aimed to investigate the influence of oral contraceptives (OC) on the pharmacokinetics of the protease inhibitor saquinavir. METHODS: Saquinavir was administered in a hard gelatin capsule formulation (Invirase) to rule out confounding by pharmaceutical aids of the more frequently used soft gelatin capsule. After an overnight fast, eight healthy female participants ingested a single oral dose of 600 mg saquinavir immediately before and after the 19th dose of a combined, low dose OC (0.03 mg ethinylestradiol, 0.075 mg gestodene) in a prospective, fixed sequence study design. The first saquinavir application was scheduled on day 1, 2, or 3 of the individual menstrual cycle. Plasma concentrations of saquinavir and relative concentrations of its M2&M3-hydroxy metabolites were determined by LC/MS/MS for 48 h. RESULTS: Intake of OC resulted in a significant decrease in morning serum concentrations (before intake of OC, compared to day 19 of OC therapy) of 17beta-estradiol by -23.4 pg ml-1 (57%, 95%CI: -76% to -37.4%); progesterone by -0.25 ng ml-1 (33%, 95%CI: -45.3% to -21.5%); follicle-stimulating hormone by -4.06 U l-1 (82%, 95%CI: -96.5% to -67.7%); and luteinizing hormone by -3.49 U l-1 (74%, 95%CI: -93 to -54.6%). Conversely, sexual hormone binding globulin serum concentrations increased by 83.6 nmol l-1 (205%, 95%CI: 32.2% to 377%). Pharmacokinetic parameters of saquinavir (AUC, Cmax, tmax, t1/2, CLR) were not affected by OC, nor was the relative metabolic ratio of saquinavir/M2&M3-hydroxy saquinavir. Furthermore, there was no association of serum hormone concentrations or MDR1-polymorphisms (C3435T and G2677T) with pharmacokinetic parameters of saquinavir. CONCLUSIONS: There was no effect of OC on saquinavir pharmacokinetics. Thus, pharmacokinetic interactions of synthetic sexual steroids with saquinavir are not likely to account for the increased ADR to antiretroviral therapy seen in women.

Adult↗

Pregnancy complications, obstetric risks, and neonatal outcome in singleton and twin pregnancies after GIFT and IVF.

PURPOSE: In vitro fertilization (IVF) and to a lower extent gamete intra-fallopian transfer (GIFT) have become routine infertility treatments in industrialized countries. Our purpose is to compare the obstetric and neonatal characteristics of singleton and twin pregnancies after GIFT and IVF with those conceived spontaneously. METHODS: This case-control study was conducted in a tertiary care medical center. The 322 singleton and 78 twin pregnancies after GIFT or IVF from 1991 through 1996 were evaluated and compared with each other, and with a control group that conceived spontaneously and matched for parity, maternal and gestational age. Statistical significance of differences was assessed by chi(2) test or two-tailed Fisher exact test. Continuous variables were compared by the paired t-test. RESULTS: Pregnancy-induced hypertension (PIH) and vaginal bleeding were significantly more frequent maternal complications in the GIFT/IVF singleton groups compared to controls. In twin pregnancies the rate of cesarean sections, vaginal bleeding and preterm labor were more common after GIFT/IVF but did not reach statistical significance. Assisted reproduction was associated with low birth weight only in twin pregnancies when controlled for confounding variables, however perinatal outcome was comparable. There was no significant difference in the outcome measures between GIFT and IVF pregnancies. CONCLUSION: After controlling for parity, maternal and gestational age, singleton pregnancies conceived by GIFT/IVF are at increased obstetrical risk, however the perinatal outcome is comparable despite a lower average birth weight.

Case-Control Studies↗