Thymopentin treatment of murine premature ovarian failure via attenuation of immune cell activity and promotion of the BMP4/Smad9 signalling pathway

Abstract

Premature ovarian failure (POF) is a typical form of pathological aging with complex pathogenesis and no effective treatment. Meanwhile, recent studies have reported that a high-fat and high-sugar (HFHS) diet adversely affects ovarian function and ovum quality. Here, we investigated the therapeutic effect of thymopentin (TP-5) as a treatment for murine POF derived from HFHS and its target. Pathological examination and hormone assays confirmed that TP-5 significantly improved murine POF symptoms. And, TP-5 could reduce oxidative stress injury and blood lipids in the murine POF derived from HFHS. Flow cytometry and qPCR results suggested that TP-5 attenuated activation of CD3+ T cells and type I macrophages. RNA-Seq results indicated somedifferences in gene transcription between the TP-5 intervention group and the control group. KEGG analysis indicated that the expression of genes involved in the mTOR signaling pathway was the most significantly different between the two groups. Additionally, compared with the control groups, the expression levels of interleukin, NFκB, and TNF families of genes were significantly downregulated in the POF+TP-5 group, whereas expression of the TGFβ/Smad9 genes was significantly upregulated. Finally, immunofluorescence staining and qPCR confirmed that TP-5 promoted the polarization of Mø2 cells in the ovary by activating the expression of the BMP4/Smad9 signalling pathway. Thus, our study confirmed that TP-5 has a significant therapeutic effect on POF by upregulating BMP4/Smad9 signalling pathway so as to promote the balance and polarization of immune cell and reducing the release of inflammatory factors and reduce lipid oxidative stress injury.

Electroacupuncture May Inhibit Oxidative Stress of Premature Ovarian Failure Mice by Regulating Intestinal Microbiota

“…Our past work demonstrated that POF was a result of pathological ovarian aging and it had very close contact with HFHS-induced oxidative stress [ 7 – 9 ]. Currently, EA is an effective strategy for the treatment of POF.…”

“…This is consistent with previous research [ 22 , 23 ]. In addition, HFHS diet could induce oxidative stress in the female reproductive system [ 7 – 9 ]. Oxidative stress was defined as an imbalance between ROS production and the antioxidant capacity of cell [ 33 ].…”

“…According to our previous studies [7][8][9], when the mice showed low levels of estradiol (E2) and/or high levels of follicle-stimulating hormone (FSH) and ovarian pathologies presented as mature ovarian follicles disappeared and the proportion of atretic follicles significantly increased, the establishment POF mice model induced by HFHS is successful. HE staining results suggested that a large number of atresia follicles (orange arrows) and fat vacuoles (black arrow) were present in ovary tissues of the POF Compared with the POF group, the proportion of atretic follicles was significantly decreased (P < 0:001), while the proportion of normal follicles was significantly increased (P < 0:001), and matured follicles (green arrows) were found in ovary tissues of the EA group (Figures 1(a), 1(d), and 1(e)).…”

“…Recent studies found that dietary and environmental factors are closely associated with the development of POF [2,3], and a high-fat and highsugar (HFHS) diet impairs the function of ovary and the quality of ovum [4][5][6]. Our previous studies have demonstrated that HFHS can induce oxidative stress and HFHS is a risk factor in the POF [7][8][9]. Ferroptosis is a new form of programmed cell death that is closely related to irondependent lipid peroxidation and reactive oxygen species (ROS) dependent [10,11].…”

Beneficial Effects of Traditional Chinese Medicine in the Treatment of Premature Ovarian Failure

“…Lipid oxidative stress injury and polarization of immune cells are inhibited and the release of inflammatory factors is increased in POF mice. Zhu et al reported that the concentrations of IL-1 β , IL-6, IL-4, IL-22, NF- κ B, TNF- α and IFN- γ in the peripheral blood of POF mice were significantly decreased after thymopentin treatment [ 52 ]. Yin et al reported that Th17/Tc17 cells, Th17/Treg cells, or IL-17 expression were increased, restoring ovarian function after human placenta mesenchymal stem cells were transplanted into POF mice [ 53 ].…”