Scott Hailey, Martinelli Lilian M, Grynspan David, Bloise Enrrico, Connor Kristin L
Department of Health Sciences, Carleton University, Ottawa, Canada.
Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil.
J Clin Endocrinol Metab. 2022 Mar 24;107(4):1140-1158. doi: 10.1210/clinem/dgab813.
Preterm birth (PTB) and suboptimal prepregnancy body mass index (BMI) operate through inflammatory pathways to impair fetoplacental development. Placental efflux transporters mediate fetal protection and nutrition; however, few studies consider the effect of both PTB and BMI on fetal protection. We hypothesized that PTB would alter the expression of placental multidrug resistance (MDR) transporters and selected proinflammatory cytokines, and that maternal underweight and obesity would further impair placental phenotype.
To determine whether placental MDR transporters P-glycoprotein (P-gp, encoded by ABCB1) and breast cancer resistance protein (BCRP/ABCG2), and proinflammatory cytokine levels are altered by PTB and maternal BMI.
A cross-sectional study was conducted to assess the effect of PTB (with/without chorioamnionitis), or the effect of maternal prepregnancy BMI on placental MDR transporter and interleukin (IL)-6 and -8 expression in 60 preterm and 36 term pregnancies.
ABCB1 expression was increased in preterm compared to term placentae (P = .04). P-gp (P = .008) and BCRP (P = .01) immunolabeling was increased among all preterm compared to term placentae, with P-gp expression further increased in preterm pregnancies with chorioamnionitis (PTC, P = .007). Placental IL-6 mRNA expression was decreased in PTC compared to term placentae (P = .0005) and PTC associated with the greatest proportion of anti-inflammatory medications administered during pregnancy. Maternal BMI group did not influence placental outcomes.
PTB and infection, but not prepregnancy BMI, alter placental expression of MDR transporters and IL-6. This may have implications for fetal exposure to xenobiotics that may be present in the maternal circulation in pregnancies complicated by PTB.
早产(PTB)和孕前体重指数(BMI)不理想会通过炎症途径损害胎儿胎盘发育。胎盘外排转运蛋白介导胎儿保护和营养;然而,很少有研究考虑早产和BMI对胎儿保护的综合影响。我们假设早产会改变胎盘多药耐药(MDR)转运蛋白和某些促炎细胞因子的表达,并且母亲体重过轻和肥胖会进一步损害胎盘表型。
确定早产和母亲BMI是否会改变胎盘MDR转运蛋白P-糖蛋白(P-gp,由ABCB1编码)和乳腺癌耐药蛋白(BCRP/ABCG2)以及促炎细胞因子水平。
进行了一项横断面研究,以评估早产(有无绒毛膜羊膜炎)或母亲孕前BMI对60例早产和36例足月妊娠胎盘MDR转运蛋白以及白细胞介素(IL)-6和-8表达的影响。
与足月胎盘相比,早产胎盘的ABCB1表达增加(P = 0.04)。与足月胎盘相比,所有早产胎盘的P-gp(P = 0.008)和BCRP(P = 0.01)免疫标记增加,绒毛膜羊膜炎早产(PTC)妊娠的P-gp表达进一步增加(P = 0.007)。与足月胎盘相比,PTC的胎盘IL-6 mRNA表达降低(P = 0.0005),且PTC与孕期使用抗炎药物比例最高相关。母亲BMI组不影响胎盘结局。
早产和感染而非孕前BMI会改变MDR转运蛋白和IL-6的胎盘表达。这可能影响胎儿暴露于早产合并妊娠母体循环中可能存在的外源性物质。