Inner Mongolia Key Laboratory of Basic Veterinary Science, Inner Mongolia Agricultural University, Hohhot, China.
Department of Basic Medicine, Inner Mongolia Medical University, Hohhot, China.
PLoS One. 2021 Nov 18;16(11):e0260188. doi: 10.1371/journal.pone.0260188. eCollection 2021.
Chronic inflammation can cause oviduct mucosal damage and immune dysfunction, leading to infertility, early pregnancy loss, ectopic pregnancy, tumors, and a decrease in reproductive capacities in female animals. Estrogen can suppress immune responses in different tissues and oviducts, and regulate the oviduct immune balance; however, the underlying mechanisms remain unclear. The objective of this study was to explore the mechanism of estrogen-regulated oviduct mucosal immunity and discover new estrogen targets for regulating oviduct mucosal immune homeostasis. Sheep oviduct epithelial cells (SOECs) were treated with 17-β estradiol (E2). Transcriptome sequencing and analysis showed differentially expressed S100 calcium-binding protein A (S100A) genes that may participate in the oviduct mucosa immunoregulation of estrogen. Quantitative polymerase chain reaction and immunocytochemistry analysis showed that S100A8 expression changed dynamically in E2-treated SOECs and peaked after 7 h of treatment. Estrogen nuclear receptors and G protein-coupled membrane receptors promoted E2-dependent S100A8 upregulation. The S100A8 gene was disrupted using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 method. Levels of inflammatory factors interleukin (IL)-1β and IL-4 were significantly upregulated in S100A8-knockdown SOECs, whereas those of the anti-inflammatory factor IL-10 was downregulated. Following S100A8 knockdown in SOECs treated with E2 for 7 h, IL-10 levels increased significantly. Estrogen affected oviduct mucosa immune function and dynamically regulated S100A8 in SOECs. S100A8 knockdown caused an excessive immune response, indicating that S100A8 is beneficial for maintaining immune homeostasis in the oviduct mucosa. Moreover, estrogen can compensate for the effect of S100A8 knockdown by upregulating IL-10.
慢性炎症可导致输卵管黏膜损伤和免疫功能障碍，导致不孕、早期妊娠丢失、宫外孕、肿瘤以及雌性动物生殖能力下降。雌激素可以抑制不同组织和输卵管的免疫反应，并调节输卵管免疫平衡；然而，其潜在机制尚不清楚。本研究旨在探讨雌激素调控输卵管黏膜免疫的机制，并发现新的雌激素靶点，以调节输卵管黏膜免疫稳态。用 17-β 雌二醇（E2）处理绵羊输卵管上皮细胞（SOECs）。转录组测序和分析显示，差异表达的 S100 钙结合蛋白 A（S100A）基因可能参与雌激素对输卵管黏膜的免疫调节。定量聚合酶链反应和免疫细胞化学分析显示，E2 处理的 SOECs 中 S100A8 表达呈动态变化，处理 7 h 后达到峰值。雌激素核受体和 G 蛋白偶联膜受体促进 E2 依赖性 S100A8 上调。使用簇状规则间隔短回文重复（CRISPR）/CRISPR 相关蛋白 9 方法破坏 S100A8 基因。S100A8 敲低的 SOECs 中白细胞介素（IL）-1β和 IL-4 等炎症因子水平显著上调，而抗炎因子 IL-10 水平下调。在 E2 处理 7 h 的 S100A8 敲低 SOECs 中，IL-10 水平显著增加。雌激素影响输卵管黏膜免疫功能，并在 SOECs 中动态调节 S100A8。S100A8 敲低导致免疫反应过度，表明 S100A8 有利于维持输卵管黏膜免疫稳态。此外，雌激素可以通过上调 IL-10 来补偿 S100A8 敲低的作用。
