Pre-eclampsia is associated with elevated CXCL12 levels in placental syncytiotrophoblasts and maternal blood.

OBJECTIVES: Placental derived vasculogenic/angiogenic substances in maternal blood are dysregulated in pre-eclampsia. We hypothesized that CXCL12, a chemokine with vasculogenic actions, is amongst such molecules. STUDY DESIGN: CXCL12, CXCL16, CXCR4, and CXCR6 immunolocalization in placental tissue was analyzed in pre-eclampsia (n=8) in comparison to controls (n=8). CXCL12, measured by ELISA in blood, in women diagnosed with pre-eclampsia (n=14) and prior to the development of pre-eclampsia (at 20 weeks' gestation, n=20) was compared with CXCL12 concentrations in gestation-matched, healthy control subjects (n=34). RESULTS: In placental tissue, syncytiotrophoblast staining for CXCL12 was increased in pre-eclampsia. Maternal serum CXCL12 was increased in pre-eclampsia [2000 (SD 402) vs 1484 (SD 261)pg/ml, P=0.01] but not in plasma obtained at 20 weeks of gestation prior to the onset of pre-eclampsia [1183 (SD 336) vs 1036 (SD 144)pg/ml, P=0.09]. CONCLUSION: Our data suggest that the syncytiotrophoblast contributes to a pre-eclampsia-associated increase in CXCL12 levels in maternal blood. These findings support the hypothesis that an imbalance of angiogenic factors contributes to the pathogenesis of pre-eclampsia.

Impact of female and male obesity on IVF/ICSI: results of 700,000 ART-cycles in Germany.

To our knowledge, this is the first analysis in which male and female weights have been combined. The registry dataset covering a 12-year period was analysed for all treatment cycles where an embryo transfer was reported. In all, 706,360 cycles were analysed. Treatments include IVF, ICSI, IVF/ICSI and CPE. The highest success rate in IVF cycles was found in couples, with an obese male partner. In the group of obese women, the pregnancy rate decreased to 27.2%. Similar to IVF treatment, the highest success rate in ICSI cycles was found in couples, where either the male or the female partner was obese. The highest success rate in cycles with a cryopreserved embryo transfer was observed in couples where both partner were obese. The lowest success rate was seen where the female partner was obese. Our data analysis suggests that the combination of an obese male and a normal-weight female is positively related to better implantation rates in IVF as well as ICSI-cycles. This combination is more likely to be found in couples with a higher social status. Therefore, the increased pregnancy rate in this group might as well be related to other lifestyle factors associated with higher social status.

Expression of the vascular endothelial growth factor receptor neuropilin-1 at the human embryo-maternal interface.

OBJECTIVE: Angiogenesis is required for successful implantation of the invading blastocyst. Vascular endothelial growth factor (VEGF) is an important key player in angiogenesis and vascular remodeling during the implantation process. Besides its well-characterized receptors VEGFR1 and VEGFR2, neuropilin-1 (NRP-1) has been shown to play an additional role in the signaling process of angiogenesis in human endometrium during the menstrual cycle, as a co-receptor of VEGF. These findings led to the hypothesis that NRP-1 might play a role in the vascular remodeling process during embryo implantation and the establishment of a pregnancy. STUDY DESIGN: NRP-1 mRNA transcript and protein expression were investigated in human choriocarcinoma cell lines (JEG-3, Jar and BeWo) aiming to evaluate the expression of NRP-1 in vitro, as well as in human decidua of all three trimesters of pregnancy, by western blot analysis (three samples of each trimester of pregnancy). The localization of NRP-1 in human decidua of all three trimesters of pregnancy was analyzed by immunohistochemistry (five samples of each trimester of pregnancy). RESULTS: NRP-1 transcript and protein were expressed in all cell lines examined. Corresponding to the analysis of human tissue by western blot and the localization by immunohistochemistry, NRP-1 protein higher expressed in samples of early pregnancy in comparison to the end of pregnancy. NRP-1 was expressed in the decidua, villi and invading cytotrophoblast of all samples investigated. CONCLUSIONS: This is the first study clearly showing the expression of NRP-1 in human decidua and trophoblast, suggesting an important role for the VEGF co-receptor NRP-1 besides the established receptor VEGFR2 at the embryo-maternal interface during embryonic implantation and placentation.

Effect of oral N-acetyl cysteine on recurrent preterm labor following treatment for bacterial vaginosis.

OBJECTIVE: To evaluate the effect of N-acetyl cysteine (NAC) on gestational age at delivery in women with previous preterm labor and bacterial vaginosis. METHODS: A randomized, double-blind, placebo-controlled trial with 280 women between 16 and 18 weeks of pregnancy who had 1 previous preterm birth and had just been successfully treated for bacterial vaginosis with metronidazole for 1 week. The women were randomized to receive 0.6 g of NAC per day plus 17-hydroxyprogesterone caproate (17-OHPC) or placebo plus 17-OHPC until 36 completed weeks of pregnancy or active labor. A vaginal swab was taken during labor. RESULTS: Reaching 36 weeks of pregnancy was more frequent (P<0.05) and gestational age at delivery was significantly higher in the NAC than in the placebo group (37.4 weeks+/-0.4 weeks vs 34.1 weeks+/-1.2 weeks, P<0.05). The discontinuation rate was 11.4% in the NAC group. CONCLUSIONS: Oral NAC was found to reduce the recurrence of preterm birth in patients with bacterial vaginosis.

Interleukin-1beta regulation of gonadotropin-releasing hormone messenger ribonucleic acid in cultured human endometrial stromal cells.

OBJECTIVE: To investigate the role of interleukin-1beta (IL-1beta) in regulating GnRH mRNA expression in cultured human endometrial stromal cells using a modified semiquantitative competitive reverse transcription and polymerase chain reaction (PCR). DESIGN: A controlled study. SETTING: Clinical and academic research setting in a university medical center. PATIENT(S): Women undergoing hysterectomy for nonmalignant indications. INTERVENTION(S): Confluent stromal cell cultures treated with steroid hormones were stimulated with IL-1beta and attenuated by anti-IL-1beta antibody or IL-1 receptor antagonist. MAIN OUTCOME MEASURE(S): The human endometrial stromal cell expression of GnRH and its receptor were determined by PCR. Interleukin-1beta-mediated regulation of stromal cell GnRH mRNA expression was determined by quantitative competitive PCR. RESULT(S): The GnRH and GnRH receptor mRNA expression were amplified in cultured stromal cells by PCR and two rounds of nested PCR, respectively. Treatment with IL-1beta stimulated stromal cell GnRH mRNA expression at concentrations of IL-1beta above 10 IU/mL. Recombinant IL-1 receptor antagonist and anti-IL-1beta antibody attenuated the increase of gene expression of GnRH initiated by IL-1beta. CONCLUSION(S): These results provide indirect evidence that IL-1beta may play a crucial role at the level of embryo-maternal interaction by regulating stromal cell expression of GnRH and its receptor, both known to be important in mediating trophoblast invasion and placental hormone regulation.