Department of Pediatrics, Alberta Health Services, Calgary, AB, Canada.
Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Am J Reprod Immunol. 2021 Jun;85(6):e13382. doi: 10.1111/aji.13382. Epub 2020 Dec 16.
Cigarette smoking during pregnancy is associated with reduced incidence of preeclampsia. Mechanisms of this association are poorly understood. Cytokines, angiogenic, and anti-angiogenic factors are involved in the pathogenesis of preeclampsia. During normal pregnancy, Fas ligand (FasL) present on trophoblasts induces apoptosis of Fas bearing maternal immune cells. In preeclampsia, trophoblasts show increased apoptosis with reduced expression of FasL. We determined serum levels of cytokines, angiogenic (placental growth factor), anti-angiogenic factors (soluble endoglin, soluble fms-like tyrosine kinase-1), soluble Fas (sFas), and soluble FasL (sFasL) in smoking and non-smoking pregnant women.
Using enzyme-linked immunosorbent and multiplex assays, we prospectively analyzed serum levels of angiogenic, anti-angiogenic factors, cytokines, sFas and sFasL in normotensive smoking and non-smoking mothers. Exclusion criteria included maternal hypertension, auto-immune disorders, rupture of membranes, evidence of labor, and drug use.
Of 100 women recruited to the study, 51 were in the non-smoking and 49 in the smoking group. Except for lower maternal age in the smoking group, there was no difference in gestation, BMI, gravidity, or ethnicity between the two groups. Levels of angiogenic, anti-angiogenic factors, cytokines, and sFas were similar between the two groups but sFasL levels were significantly higher in smoking group (38 pg/ml vs. 16 pg/ml, p < .001) and remained significant after controlling for confounders.
Our study demonstrates higher sFasL levels in pregnant women who smoke. Higher sFasL may explain the reduced incidence of preeclampsia in pregnant mothers who smoke by inducing apoptosis of immune cells which may otherwise induce trophoblast apoptosis.
孕期吸烟与子痫前期发病率降低有关。这种关联的机制尚不清楚。细胞因子、血管生成和抗血管生成因子参与子痫前期的发病机制。在正常妊娠中，滋养细胞上的 Fas 配体 (FasL) 诱导 Fas 阳性的母体免疫细胞凋亡。在子痫前期，滋养细胞凋亡增加，FasL 表达减少。我们测定了吸烟和非吸烟孕妇血清中的细胞因子、血管生成（胎盘生长因子）、抗血管生成因子（可溶性内皮素、可溶性 Fms 样酪氨酸激酶-1）、可溶性 Fas（sFas）和可溶性 FasL（sFasL）水平。
我们前瞻性地分析了正常血压吸烟和非吸烟母亲的血清中血管生成、抗血管生成因子、细胞因子、sFas 和 sFasL 的水平，使用酶联免疫吸附和多重分析。排除标准包括母体高血压、自身免疫性疾病、胎膜破裂、有分娩迹象和药物使用。
在招募的 100 名女性中，51 名在非吸烟组，49 名在吸烟组。除了吸烟组的母亲年龄较低外，两组在妊娠、BMI、孕次或种族方面没有差异。两组的血管生成、抗血管生成因子、细胞因子和 sFas 水平相似，但吸烟组的 sFasL 水平明显更高（38 pg/ml 比 16 pg/ml，p <.001），且在控制混杂因素后仍然显著。
我们的研究表明，吸烟孕妇的 sFasL 水平更高。较高的 sFasL 通过诱导免疫细胞凋亡来解释吸烟孕妇子痫前期发病率降低的现象，否则免疫细胞可能会诱导滋养细胞凋亡。
