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Poster session I Clinical obstetrics, epidemiology, fetus, medical-surgical complications, neonatalogy, physiology/endocrinology, prematurity: Abstracts 87 - 236| Volume 208, ISSUE 1, SUPPLEMENT , S107, January 01, 2013

234: Inhibition of autophagy by sera from pregnant women

      Objective

      Autophagy is a process that maintains homeostasis by eliminating senescent or damaged intracellular organelles and proteins. In addition, autophagy participates in regulation of innate and acquired immunity. A role for autophagy in pregnancy has been scarcely studied. We compared the influence of sera from pregnant and non-pregnant women on autophagy induction. p62 is a cytoplasmic protein essential for induction of autophagy. Its concentration in the cytoplasm is inversely proportional to the level of autophagy induction.

      Study Design

      Peripheral blood mononuclear cells (PBMCs) from female donors were incubated with sera from 35 women in the second trimester of pregnancy or 35 non-pregnant reproductive age women. After 48 hours cells were collected, lysed and assayed for p62 concentrations by ELISA. PBMCs were also incubated with the autophagy inducer, rapamycin, in the presence or absence of sera. Sera were tested for concentrations of immune mediators by ELISA. Clinical data and source of sera were accessed only after completion of all experiments.

      Results

      Median (range) p62 concentrations were 6.7 ng/ml (1.1-22.7) for PBMCs incubated with pregnancy sera vs. 2.5 ng/ml (0.8-7.7) for non-pregnant sera (p<0.0001). Even in the presence of rapamycin, median p62 levels were elevated in the presence of pregnancy sera, 1.3 ng/ml (0.06-4.9), as compared to non-pregnant sera, 0.7 ng/ml (0-3.3) (p=0.0191). Among the pregnant subjects, the p62 level was inversely proportional to the results of a 50 g glucose challenge test (GCT) (r = −0.5630, p=0.0005). Insulin-like growth factor-1 and interleukin-13, inhibitors of autophagy, were elevated in sera from pregnant women.

      Conclusion

      Sera from healthy pregnant women inhibit autophagy to a greater extent than sera from non-pregnant women. Autophagy inhibition during pregnancy may function to decrease insulin resistance.