Spontaneous abortion is associated with elevated systemic C5a and reduced mRNA of complement inhibitory proteins in placenta.

Spontaneous abortion in early pregnancy due to unknown reasons is a common problem. The excess complement activation and consequent placental inflammation and anti-angiogenic milieu is emerging as an important associated factor in many pregnancy-related complications. In the present study we sought to examine the expression of complement inhibitory proteins at the feto-maternal interface and levels of complement split products in the circulation to understand their role in spontaneous abortion. Consenting pregnant women who either underwent elective abortion due to non-clinical reasons (n = 13) or suffered miscarriage (n = 14) were recruited for the study. Systemic levels of complement factors C3a and C5a were measured by enzyme-linked immunosorbent assay (ELISA). Plasma C5 and C3 protein levels were examined by Western blot. Expressions of complement regulatory proteins such as CD46 and CD55 in the decidua were investigated by quantitative polymerase chain reaction (PCR) and Western blot. The median of plasma C3a level was 82·83 ng/ml and 66·17 ng/ml in elective and spontaneous abortion patients, respectively. Medians of plasma C5a levels in elective and spontaneous abortion patients were 0·96 ng/ml and 1·14 ng/ml, respectively. Only plasma C5a levels but not C3a levels showed significant elevation in spontaneous abortion patients compared to elective abortion patients. Further, there was a threefold decrease in the mRNA expressions of complement inhibitory proteins CD46 and CD55 in the decidua obtained from spontaneous abortion patients compared to that of elective abortion patients. These data suggested that dysregulated complement cascade may be associated with spontaneous abortion.

Cut mutant Drosophila auditory organs differentiate abnormally and degenerate.

The Drosophila antenna is a sophisticated structure that functions in both olfaction and audition. Previous studies have identified Homothorax, Extradenticle, and Distal-less, three homeodomain transcription factors, as required for specification of antennal identity. Antennal expression of cut is activated by Homothorax and Extradenticle, and repressed by Distal-less. cut encodes the Drosophila homolog of human CAAT-displacement protein, a cell cycle-regulated homeodomain transcription factor. Cut is required for normal development of external mechanosensory structures and Malphigian tubules (kidney analogs). The role of cut in the Drosophila auditory organ, Johnston's organ, has not been characterized. We have employed the FLP/FRT system to generate cut null clones in developing Johnston's organ. In cut mutants, the scolopidial subunits that constitute Johnston's organ differentiate abnormally and subsequently degenerate. Electrophysiological experiments confirm that adult Drosophila with cut null antennae are deaf. We find that cut acts in parallel to atonal, spalt-major, and spalt-related, which encode other transcription factors required for Johnston's organ differentiation. We speculate that Cut functions in conjunction with these factors to regulate transcription of as yet unidentified targets.