MicroRNA-146 attenuates lipopolysaccharide induced ovarian dysfunction by inhibiting the TLR4/NF- κB signaling pathway

Abstract

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.

Protective effect of Luffa cylindrica fermentation liquid on cyclophosphamide-induced premature ovarian failure in female mice by attenuating oxidative stress, inflammation and apoptosis

“…Our present data found that LF reduced the expressions of critical genes and proteins in the TLR4/NF-κB signaling pathway in the ovaries of POF mice. These findings were similar to those from the previous literature [ 34 – 36 ]. It may be concluded that LF could prevent CTX-induced ovarian inflammation response via a TLR4/NF-κB dependent mechanism.…”

OX-LDL promotes insufficient autophagy and apoptosis of ovarian granulosa cells through regulation ROS-mediated PI3K/Akt/mTOR pathway

“…Recent studies have shown that oxidative stress is also related to human reproductive system diseases [4]. In POI, inflammation reaction and oxidative stress affect the quality of follicles [5]. Oxidative stress during ovarian aging is an important pathogenesis [6].…”