Institute of Reproductive Biology, Leibniz Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany.
Institute of Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany.
Int J Mol Sci. 2020 Jan 10;21(2):443. doi: 10.3390/ijms21020443.
Maternal stress before or during the sensitive preimplantation phase is associated with reproduction failure. Upon real or perceived threat, glucocorticoids (classic stress hormones) as cortisol are synthesized. The earliest "microenvironment" of the embryo consists of the oviduct epithelium and the oviductal fluid generated via the epithelial barrier. However, to date, the direct effects of cortisol on the oviduct are largely unknown. In the present study, we used a compartmentalized in vitro system to test the hypothesis that a prolonged stimulation with cortisol modifies the physiology of the oviduct epithelium. Porcine oviduct epithelial cells were differentiated at the air-liquid interface and basolaterally stimulated with physiological levels of cortisol representing moderate and severe stress for 21 days. Epithelium structure, transepithelial bioelectric properties, and gene expression were assessed. Furthermore, the distribution and metabolism of cortisol was examined. The polarized oviduct epithelium converted basolateral cortisol to cortisone and thereby reduced the amount of bioactive cortisol reaching the apical compartment. However, extended cortisol stimulation affected its barrier function and the expression of genes involved in hormone signaling and immune response. We conclude that continuing maternal stress with long-term elevated cortisol levels may alter the early embryonic environment by modification of basic oviductal functions.
母体在着床前敏感阶段之前或期间的压力与生殖失败有关。在真正或感知到威胁时,糖皮质激素(经典应激激素)如皮质醇被合成。胚胎的最早“微环境”由输卵管上皮和通过上皮屏障产生的输卵管液组成。然而,迄今为止,皮质醇对输卵管的直接影响在很大程度上尚不清楚。在本研究中,我们使用了一个分隔的体外系统来测试以下假设,即皮质醇的长期刺激会改变输卵管上皮的生理学。猪输卵管上皮细胞在气液界面分化,并在基底外侧用代表中度和重度应激的生理水平的皮质醇刺激 21 天。评估了上皮结构、跨上皮生物电特性和基因表达。此外,还检查了皮质醇的分布和代谢。极化的输卵管上皮将基底外侧的皮质醇转化为可的松,从而减少到达顶端隔室的生物活性皮质醇的量。然而,皮质醇的长期刺激会影响其屏障功能以及参与激素信号和免疫反应的基因的表达。我们得出结论,持续的母体压力伴随着长期升高的皮质醇水平可能通过改变基本的输卵管功能来改变早期胚胎环境。