Interpregnancy interval and abnormally invasive placentation.

INTRODUCTION: The presence of a previous uterine scar is a strong risk factor for developing abnormally invasive placentation (AIP). We sought to determine whether a short interpregnancy interval predisposes to AIP. We hypothesized that a short interpregnancy interval after a previous cesarean delivery increases the risk of AIP in comparison with a longer interpregnancy interval. MATERIAL AND METHODS: We performed a retrospective cohort study of women with a histological diagnosis of AIP and a history of a previous cesarean section. Women were included in the control group if they had a previous cesarean section with a placenta underlying the previous uterine scar or an anterior previa. The time interval between pregnancy and AIP data was analyzed using the chi-square test and two-tailed Fisher's exact test. RESULTS: There was no statistical difference in the interpregnancy interval between women who had AIP vs the control group. Gravidity and parity were found to be significantly higher in the women with AIP vs the controls. CONCLUSIONS: These results suggest that a short interpregnancy interval may not increase the risk of developing AIP.

Human trophoblast epithelial-mesenchymal transition in abnormally invasive placenta.

Differentiation of first trimester human placental cytotrophoblast (CTB) from an anchorage-dependent epithelial phenotype into the mesenchymal-like invasive extravillous trophoblast (EVT) is crucial in the development of the maternal-fetal interface. We showed previously that differentiation of first trimester CTB to EVT involves an epithelial-mesenchymal transition (EMT). Here we compare the epithelial-mesenchymal characteristics of CTB and EVT derived from normal third trimester placenta or placenta previa versus abnormally invasive placenta (AIP). CTB and EVT were isolated from normal term placenta or placenta previa following Caesarean section and EVT from AIP following Caesarean hysterectomy. Cell identity was validated by measurement of cytokeratin-7 and HLA-G. Comparing normal term CTB with EVT from normal term placenta or placenta previa for differential expression analysis of genes associated with the EMT showed changes in >70% of the genes probed. While demonstrating a mesenchymal phenotype relative to CTB, many of the gene expression changes in third trimester EVT were reduced relative to the first trimester EVT. We suggest that third trimester EVT are in a more constrained, metastable state compared to first trimester equivalents. By contrast, EVT from AIP demonstrate characteristics that are more mesenchymal than normal third trimester EVT, placing them closer to first trimester EVT on the EMT spectrum, consistent with a more invasive phenotype.

Using cellular fitness to map the structure and function of a major facilitator superfamily effluxer.

The major facilitator superfamily (MFS) effluxers are prominent mediators of antimicrobial resistance. The biochemical characterization of MFS proteins is hindered by their complex membrane environment that makes in vitro biochemical analysis challenging. Since the physicochemical properties of proteins drive the fitness of an organism, we posed the question of whether we could reverse that relationship and derive meaningful biochemical parameters for a single protein simply from fitness changes it confers under varying strengths of selection. Here, we present a physiological model that uses cellular fitness as a proxy to predict the biochemical properties of the MFS tetracycline efflux pump, TetB, and a family of single amino acid variants. We determined two lumped biochemical parameters roughly describing Km and Vmax for TetB and variants. Including in vivo protein levels into our model allowed for more specified prediction of pump parameters relating to substrate binding affinity and pumping efficiency for TetB and variants. We further demonstrated the general utility of our model by solely using fitness to assay a library of tet(B) variants and estimate their biochemical properties.