Affiliated Dongguan Maternal and Child Health Hospital, Southern Medical University, Guangzhou, China.
Affiliated HuaDu Hospital, Southern Medical University, Guangzhou, China.
Bioengineered. 2022 May;13(5):11611-11623. doi: 10.1080/21655979.2022.2070584.
Premature ovarian insufficiency (POI) is a disease that seriously affects women's reproductive function and even leads to lifelong infertility. Little is known about the mechanism of lipopolysaccharide (LPS)-induced ovarian dysfunction. Thus, we aimed to identify the role of the up-regulation of microRNA (miRNA)-146 expression offered protection against ovarian dysfunction by inhibiting the toll-like receptor (TLR) 4, TLR4/phosphorylated (p)-nuclear factor (NF)-κB signaling pathway and inflammatory cytokine tumor necrosis factor (TNF)-a and Interleukin (IL)-6. In an in vivo study, we established an LPS-induced ovarian dysfunction mouse model. The mouse ovarian granulosa cells were transfected with miR-146 mimic or negative controls or inhibitor and then treated with LPS. Therefore, cell viability, cells apoptosis, IL-6 and TNF-a, TLR4, NF- κB were assessed, respectively. These results demonstrated that the up-regulation of miRNA-146 expression may protect against LPS-induced ovarian dysfunction and markedly increased the cell viability, and significantly reduced the ovarian granulosa cells apoptotic rate, and down-regulated IL-6 and TNF-a expression. In addition, miRNA-146 exerted protective ovarian functions might be via inhibiting TLR4/NF-κB signaling pathway. In summary, we reveal the up-regulation of miRNA-146 expression mitigated ovarian dysfunction by negatively regulating expression of the IL-6 and TNF-a, which may shed light on the potential molecular mechanisms of overexpression of miRNA-146 may reversed the ovarian dysfunction by inhibiting the TLR4/ NF-κB signaling pathway.
卵巢早衰（POI）是一种严重影响女性生殖功能的疾病，甚至导致终身不孕。人们对脂多糖（LPS）诱导的卵巢功能障碍的机制知之甚少。因此，我们旨在确定上调 microRNA（miRNA）-146 的表达通过抑制 toll 样受体（TLR）4、TLR4/磷酸化（p）-核因子（NF）-κB 信号通路和炎症细胞因子肿瘤坏死因子（TNF）-a 和白细胞介素（IL）-6 对卵巢功能障碍提供保护作用的机制。在一项体内研究中，我们建立了 LPS 诱导的卵巢功能障碍小鼠模型。将 miR-146 模拟物或阴性对照物或抑制剂转染到小鼠卵巢颗粒细胞中，然后用 LPS 处理。因此，分别评估细胞活力、细胞凋亡、IL-6 和 TNF-a、TLR4、NF-κB。这些结果表明，miRNA-146 表达的上调可能对 LPS 诱导的卵巢功能障碍具有保护作用，并显著增加细胞活力，显著降低卵巢颗粒细胞凋亡率，并下调 IL-6 和 TNF-a 的表达。此外，miRNA-146 发挥保护卵巢功能的作用可能是通过抑制 TLR4/NF-κB 信号通路。总之，我们揭示了 miRNA-146 表达的上调通过负调控 IL-6 和 TNF-a 的表达减轻卵巢功能障碍，这可能为 miRNA-146 的过度表达通过抑制 TLR4/NF-κB 信号通路逆转卵巢功能障碍的潜在分子机制提供了线索。
