title: Inhibition of autophagy by sera from pregnant women.
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.
authors.affiliation: 1Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Tomi T
authors.initials: TT
authors.lastname: Kanninen
authors.forename: Bruna Ribeiro
authors.initials: BR
authors.lastname: de Andrade Ramos
authors.forename: Shirlee
authors.initials: S
authors.lastname: Jaffe
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Bongiovanni
authors.forename: Iara Moreno
authors.initials: IM
authors.lastname: Linhares
authors.forename: Gian Carlo Di
authors.initials: GC
authors.lastname: Renzo
authors.forename: Steven S
authors.initials: SS
authors.lastname: Witkin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000328:Adult; D001343:Autophagy / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D018793:Interleukin-13 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D000071456:Sequestosome-1 Protein; D044967:Serum / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000097:blood
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C583557:IGF1 protein, human; D018836:Inflammation Mediators; D018793:Interleukin-13; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D007334:Insulin-Like Growth Factor I; D020123:Sirolimus
keywords: autophagy; insulin resistance; p62; pregnancy; rapamycin