Angiogenic factors and uterine Doppler velocimetry in early- and late-onset preeclampsia.

OBJECTIVE: To assess correlations between maternal serum levels of pro- and anti-angiogenic factors with uterine perfusion in women with early- compared with late-onset preeclampsia, and in healthy pregnant women. DESIGN: Case-control study. SETTING: Antenatal care clinic located within a hospital (São Bernardo do Campo, Brazil). POPULATION: We enrolled 54 preeclamptic and 54 healthy control women who were coming for routine ultrasound at 28-36 weeks' gestation. METHODS: All participants had uterine artery and umbilical Doppler studies and a blood sample to assess maternal serum levels of soluble fms-like tyrosine kinase-1, soluble endoglin, adiponectin and plasminogen activator inhibitor-1. All angiogenic factors were measured using enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Levels of pro- and anti-angiogenic factors in maternal serum, and uterine artery Doppler findings. RESULTS: Concentrations of soluble fms-like tyrosine kinase-1 and soluble endoglin were significantly higher in preeclamptic than control women (p < 0.0001 and p < 0.0001, respectively), especially in those with early-onset (<34 weeks) preeclampsia. These two anti-angiogenic mediators were significantly correlated with increased uterine artery Doppler in the preeclamptic women. Plasminogen activator inhibitor-1 levels were significantly higher in preeclampsia (p = 0.03) but unrelated to uterine artery resistance. Adiponectin levels were similar in cases and controls, independent of body mass index and unrelated to uterine artery resistance. CONCLUSION: Preeclamptic patients have increased soluble fms-like tyrosine kinase-1 and soluble endoglin serum levels and this increase is directly correlated with uterine artery resistance, especially in those with early-onset preeclampsia.

Getting too sweet: galectin-1 dysregulation in gestational diabetes mellitus.

Galectin-1 (gal-1) is a prototype carbohydrate-binding protein, whose dysregulation is associated with adverse pregnancy outcomes such as spontaneous abortion and pre-eclampsia. Furthermore, it is known that faulty gal-1 protein production or gene regulation can be caused by single-nucleotide polymorphisms in the LGALS1 gene. Gestational diabetes mellitus (GDM) is also an adverse pregnancy outcome and the most common metabolic disorder during gestation. However, gal-1 expression patterns during GDM remain largely unknown. Our aims were to define local and peripheral gal-1 expression patterns during pregnancy, and to investigate LGALS1 gene polymorphisms in GDM patients. Circulating gal-1 levels were determined by ELISA in GDM patients and normal pregnant controls, and LGALS1 gene polymorphisms were assessed for association with GDM. Placental tissues were collected from control and GDM term pregnancies to evaluate local gal-1 expression by immunofluorescence. Our results show that GDM is associated with a failure to increase circulating gal-1 levels during the second and third trimester, as well as overexpression of gal-1 in placental tissue. Additionally, the LGALS1 polymorphism rs4820294 was associated with the development of GDM. In pregnancies complicated by GDM, we observed gal-1 dysregulation both locally in the placenta and peripherally in the circulation. Furthermore, the association between the LGALS1 polymorphism and GDM may indicate a genetic contribution to this adverse pregnancy outcome.

Genetic polymorphisms and recurrent spontaneous abortions: an overview of current knowledge.

The relevance of gene polymorphisms in the development of unexplained recurrent spontaneous abortion is still unclear. Cytokines, angiogenic mediators, and hormones are involved in all stages of reproduction and pregnancy outcome. Impaired production and/or unbalanced ratios of these mediators have been implicated in the pathogenesis of unexplained recurrent spontaneous abortion. Functional polymorphism influence gene activity and therefore can interfere with the expression of mediators. Several studies have been carried out to evaluate the relationship between cytokines, angiogenic mediators, and hormones gene polymorphisms and unexplained recurrent spontaneous abortion. The results of these studies are mostly contradictory, and few significant associations have been identified. Up to present time, the evidence is insufficient to support the evaluation of cytokines, angiogenic mediators, and hormones gene polymorphism in routine workup in all cases of recurrent pregnancy loss, and these tests are not included in any of the major obstetric guidelines.