BACKGROUND Preeclampsia is considered a disease of immunological origin associated with abnormalities in inflammatory cytokines, tumor necrosis factor-α (TNF-α), and activated lymphocytes secreting AT1-AA. Recent studies have also demonstrated that an imbalance of angiogenic factors, soluble fms-like tyrosine kinase (sFlt-1), and sEndoglin, exists in preeclampsia; however, the mechanisms that initiate their overproduction are unclear. METHODS To determine the role of immune regulation of these factors, circulating and placental sFlt-1 and/or sEndoglin was examined from pregnant rats chronically treated with TNF-α or AT1-AA. On day 19 of gestation blood pressure was analyzed and serum and tissues were collected. Placental villous explants were excised and cultured on matrigel coated inserts for 24 h and sFlt-1 and sEndoglin was measured from media. RESULTS In response to TNF-α-induced hypertension, sFlt-1 increased from 180 ± 5 to 2,907 ± 412 pg/ml. sFlt-1 was also increased from cultured placental explants of TNF-α induced hypertensive pregnant rats (n = 12) (2,544 ± 1,132 pg/ml) vs. explants from normal pregnant (NP) rats (n = 12) (2,189 ± 586 pg/ml) where as sEng was undetectable. Circulating sFlt-1 increased from 245 ± 38 to 3,920 ± 798 pg/ml in response to AT1-AA induced hypertension. sFlt-1 levels were higher (3,400 ± 350 vs. 2,480 ± 900 pg/ml) in placental explants from AT1-AA infused rats (n = 12) than NP rats (n = 7). In addition, sEndoglin increased from 30 ± 2.7 to 44 ± 3.3 pg/ml (P < 0.047) in AT1-AA infused rats but was undetectable in the media of the placental explants. CONCLUSIONS These data suggest that immune factors may serve as an important stimulus for both sFlt-1 and sEndoglin production in response to placental ischemia.

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PURPOSE The mechanisms by which gut microbiota contribute to methylmercury metabolism remain unclear. Among a cohort of pregnant mothers, the objectives of our pilot study were to determine 1) associations between gut microbiota and mercury concentrations in biomarkers (stool, hair and cord blood) and 2) the contributions of gut microbial mercury methylation/demethylation to stool methylmercury. METHODS Pregnant women (36–39 weeks gestation, n=17) donated hair and stool specimens, and cord blood was collected for a subset (n=7). The diversity of gut microbiota was determined using 16S rRNA gene profiling (n=17). For 6 stool samples with highest/lowest methylmercury concentrations, metagenomic whole genome shotgun sequencing was employed to search for the mercury methylation gene (hgcA), and two mer operon genes involved in methylmercury detoxification (merA and merB). RESULTS Seventeen bacterial genera were significantly correlated (increasing or decreasing) with stool methylmercury, stool inorganic mercury, or hair total mercury; however, aside from one genus, there was no overlap between biomarkers. There were no definitive matches for hgcA or merB, while merA was detected at low concentrations in all six samples. MAJOR CONCLUSIONS Proportional differences in stool methylmercury were not likely attributed to gut microbiota through methylation/demethylation. Gut microbiota potentially altered methylmercury metabolism using indirect pathways.

A high LDH to AST ratio >22.12 suggests that TTP is a more likely diagnosis than HELLP syndrome in the third trimester pregnant patient, presenting with findings that could be compatible with either diagnosis. In these circumstances, it is advisable to obtain hematology consultation and to consider PEX implementation.