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Inhibition of Autophagy by Sera From Pregnant Women

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Abstract

Autophagy is a process that maintains homeostasis by eliminating senescent or damaged intracellular organelles and proteins. Its role in pregnancy has been scarcely studied. We compared the influence of sera from pregnant and nonpregnant women on autophagy induction. Peripheral blood mononuclear cells (PBMCs) were incubated with sera from 35 pregnant or nonpregnant women in the presence or absence of the autophagy inducer, rapamycin. After 48 hours, the cells were assayed for p62, a cytoplasmic protein essential for autophagy induction. Its concentration in the cytoplasm is inversely proportional to the level of autophagy induction. Sera were tested for immune mediators by enzyme-linked immunosorbent assay. Median (range) p62 concentrations were 6.7 ng/mL (1.1-22.7) for PBMCs incubated with pregnancy sera versus 2.5 ng/mL (0.8-7.7) for nonpregnant sera (P < .0001). In the presence of rapamycin, median p62 levels were 1.3 ng/mL (<0.1-4.9) with pregnancy sera, when compared to 0.6 ng/mL (<0.1-3.3) with control sera (P = .0191). Among the pregnant patients, the p62 level was inversely proportional to the results of a 50-g glucose challenge test (r = −.5630, P = .0005). Sera from pregnant women had elevated levels of insulin-like growth factor 1 (IGF-1), interleukin 13 (IL-13), and transforming growth factor β1 (TGF-β1). Autophagy during pregnancy may be inhibited by IGF-1, IL-13, and/or TGF-β1 and may influence insulin resistance.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Weill Cornell Medical College, 525 East 68th Street, Box 35, New York, NY, 10065, USA

    Tomi T. Kanninen MD, Bruna Ribeiro de Andrade Ramos MS, Shirlee Jaffe MD, Ann Marie Bongiovanni AB, Iara Moreno Linhares MD, PhD & Steven S. Witkin PhD

  2. Department of Obstetrics and Gynecology, University of Perugia, Perugia, Italy

    Tomi T. Kanninen MD & Gian Carlo Di Renzo MD, PhD

  3. Department of Gynecology and Obstetrics, University of Sao Paulo, Sao Paulo, Brazil

    Iara Moreno Linhares MD, PhD

Authors
  1. Tomi T. Kanninen MD
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  2. Bruna Ribeiro de Andrade Ramos MS
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  3. Shirlee Jaffe MD
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  4. Ann Marie Bongiovanni AB
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  5. Iara Moreno Linhares MD, PhD
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  6. Gian Carlo Di Renzo MD, PhD
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  7. Steven S. Witkin PhD
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Corresponding author

Correspondence to Steven S. Witkin PhD.

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Kanninen, T.T., de Andrade Ramos, B.R., Jaffe, S. et al. Inhibition of Autophagy by Sera From Pregnant Women. Reprod. Sci. 20, 1327–1331 (2013). https://doi.org/10.1177/1933719113485301

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