Sunny Donna Elizabeth, Hammer Elke, Ittermann Till, Krüger Elisabeth Luise, Hübner Stephanie, Hartmann Michaela Friederike, Wudy Stefan Alexander, Völker Uwe, Heckmann Matthias
Department of Neonatology and Pediatric Intensive Care, University of Medicine Greifswald, 17475 Greifswald, Germany.
Department of Functional Genomics, University of Medicine Greifswald, 17475 Greifswald, Germany.
Int J Mol Sci. 2021 Jun 19;22(12):6586. doi: 10.3390/ijms22126586.
Oxygen causes white matter damage in preterm infants and male sex is a major risk factor for poor neurological outcome, which speculates the role of steroid hormones in sex-based differences. Preterm birth is accompanied by a drop in 17β-estradiol (E2) and progesterone along with increased levels of fetal zone steroids (FZS). We performed a sex-based analysis on the FZS concentration differences in urine samples collected from preterm and term infants. We show that, in preterm urine samples, the total concentration of FZS, and in particular the 16α-OH-DHEA concentration, is significantly higher in ill female infants as compared to males. Since we previously identified Nup133 as a novel target protein affected by hyperoxia, here we studied the effect of FZS, allopregnanolone (Allo) and E2 on differentiation and Nup133 signaling using mouse-derived primary oligodendrocyte progenitor cells (OPCs). We show that the steroids could reverse the effect of hyperoxia-mediated downregulation of Nup133 in cultured male OPCs. The addition of FZS and E2 protected cells from oxidative stress. However, E2, in presence of 16α-OH-DHEA, showed a negative effect on male cells. These results assert the importance of sex-based differences and their potential implications in preterm stress response.
氧气会导致早产儿白质损伤，而男性是神经学预后不良的主要风险因素，这引发了人们对类固醇激素在性别差异中作用的推测。早产伴随着17β-雌二醇（E2）和孕酮水平下降，同时胎儿区类固醇（FZS）水平升高。我们对从早产儿和足月儿收集的尿液样本中的FZS浓度差异进行了基于性别的分析。我们发现，在早产尿液样本中，患病女婴的FZS总浓度，尤其是16α-羟基脱氢表雄酮浓度，显著高于男婴。由于我们之前将Nup133鉴定为受高氧影响的一种新的靶蛋白，因此在这里我们使用小鼠来源的原代少突胶质前体细胞（OPC）研究了FZS、别孕烯醇酮（Allo）和E2对分化及Nup133信号传导的影响。我们发现，这些类固醇可以逆转高氧介导的培养雄性OPC中Nup133下调的效应。添加FZS和E2可保护细胞免受氧化应激。然而，在存在16α-羟基脱氢表雄酮的情况下，E2对雄性细胞显示出负面影响。这些结果证实了性别差异的重要性及其在早产应激反应中的潜在影响。
