Jayaram Aswathi, Kanninen Tomi, Sisti Giovanni, Inglis Steven R, Morgan Nurah, Witkin Steven S
1 Department of Obstetrics and Gynecology, Jamaica Hospital Medical Center, Jamaica, New York, NY, USA.
2 Division of Immunology and Infectious Diseases, Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, NY, USA.
Reprod Sci. 2018 Sep;25(9):1376-1381. doi: 10.1177/1933719117746763. Epub 2017 Dec 13.
Maternal immune responses are altered during pregnancy and differ between nulliparous and multiparous women. The influence of a prior gestation on autophagy in peripheral blood mononuclear cells (PBMCs) from pregnant women has not been determined and is the subject of this investigation.
Peripheral blood mononuclear cells were isolated from 212 pregnant women and immediately lysed in the presence of protease inhibitors, and the extent of autophagy was determined by quantitation of the concentration of p62 (sequestosome-1) in the lysates by enzyme-linked immunosorbent assay (ELISA). In PBMCs, the p62 level is inversely related to the extent of autophagy. The level of the stress-inducible 70-kDa heat shock protein (hsp70), an inhibitor of autophagy, was also measured in the lysates by ELISA. Data were analyzed by the Spearman rank correlation, Mann-Whitney U test, or Kruskal-Wallis test, as appropriate.
The p62 concentration in PBMCs increased (autophagy decreased) with the number of previous live ( P = .0322), preterm ( P = .0143), or term ( P = .0418) deliveries. The p62 level was lower (autophagy higher) in women with a prior spontaneous pregnancy loss but no deliveries as compared to women with their first conception ( P = .0087). The intracellular hsp70 concentration correlated with the p62 level ( P < .0001).
Multiparity is associated with a reduced level of autophagy in PBMCs. Dysregulated autophagy might be one mechanism leading to spontaneous abortion in nulliparous women.
孕期母体免疫反应会发生改变，初产妇和经产妇之间也存在差异。既往妊娠对孕妇外周血单个核细胞（PBMCs）自噬的影响尚未明确，本研究旨在探讨这一问题。
从212名孕妇中分离出外周血单个核细胞，并立即在蛋白酶抑制剂存在的情况下进行裂解，通过酶联免疫吸附测定（ELISA）定量裂解物中p62（聚集体蛋白-1）的浓度来确定自噬程度。在PBMCs中，p62水平与自噬程度呈负相关。还通过ELISA测定了裂解物中自噬抑制剂应激诱导型70 kDa热休克蛋白（hsp70）的水平。数据根据情况采用Spearman秩相关分析、Mann-Whitney U检验或Kruskal-Wallis检验进行分析。
PBMCs中p62浓度随着既往活产（P = 0.0322）、早产（P = 0.0143）或足月产（P = 0.0418）次数的增加而升高（自噬减少）。与首次怀孕的女性相比，既往有自然流产史但未分娩的女性p62水平较低（自噬较高）（P = 0.0087）。细胞内hsp70浓度与p62水平相关（P < 0.0001）。
经产与PBMCs中自噬水平降低有关。自噬失调可能是导致初产妇自然流产的一种机制。
