RETRACTED ARTICLE: hPMSC transplantation restoring ovarian function in premature ovarian failure mice is associated with change of Th17/Tc17 and Th17/Treg cell ratios through the PI3K/Akt signal pathway

Abstract

BackgroundHuman placenta-derived mesenchymal stem cell (hPMSC) transplantation has been demonstrated to be an effective way of recovering ovarian function in mice with autoimmune induced premature ovarian failure (POF). But the exact mechanism remains unclear. The goal of the present study is to investigate the role of immune factors (T-helper 17 (Th17), cytotoxic T (Tc17) and regulatory T (Treg) cells) in the recovery of ovarian function and whether the phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway is involved in the regulation.MethodsThe inhibitor of PI3K/Akt was administered to observe its effect on ovarian function recovery and immune regulation. Serum levels of estradiol (E2), follicle stimulation hormone (FSH), luteinizing hormone (LH) and anti-Müllerian hormone (AMH)) and anti-Zona pellucida antibody (AZPAb) were measured by ELISA to evaluate ovarian function. The morphological changes of ovaries were observed by HE staining. Apoptosis of granular cells (GCs) was determined by detecting the expression of capase-3. Expression of p-Akt protein was detected by immunohistochemistry and western blot assay in ovarian tissues. The MTT assay was performed to assess GC proliferation. GC apoptosis was performed using flow cytometry analysis. Percentages of Th17, Tc17 and Treg cells were detected by flow cytometry. Expression of interleukin (IL)-17 in serum was measured by ELISA.ResultsLY294002 administration decreased serum levels of E2 and AMH, while the levels of FSH, LH and AZPAb in serum were increased compared with mice in the hPMSC transplantation group. The ovarian morphology presented as atrophy and fibrosis, with functional follicles exhausted. The expression of p-Akt in ovarian tissue was significantly decreased. Also, LY294002 administration significantly decreased proliferation and increased cell apoptosis in GCs, and for immune factors the ratios of Th17/Tc17 and Th17/Treg cells were significantly increased, as well as the serum levels of IL-17.ConclusionsOur data suggest that the PI3K/Akt signal pathway is involved in the recovery of ovarian function by changing the ratios of Th17/ Tc17 and Th17/Treg cells in POF mice following hPMSC transplantation.

Protective properties of heme oxygenase-1 expressed in umbilical cord mesenchymal stem cells help restore the ovarian function of premature ovarian failure mice through activating the JNK/Bcl-2 signal pathway-regulated autophagy and upregulating the circulating of CD8+CD28− T cells

“…FSHR, which can serve as a marker of GCs, is positive in almost all of the cells' cytoplasm ( Fig. 1f), in accordance with our previous reports [3].…”

“…The ovarian histological changes were observed by light microscopy (Olympus). We counted the follicles containing obvious nucleus in the experiment, which were divided into primordial, primary, secondary, antral, and atretic follicles, which were described before [3,34].…”

“…However, the more efficient therapeutic methods remain to be explored. With the ability of directionally differentiating into specific cells under specific microenvironments, secreting paracrine cytokines, regulating inflammation, and enhancing endogenous tissue repair [2], increasing evidences have proposed the transplantation of mesenchymal stem cells (MSCs) to be a potential therapy of treating POF disorder [3,4]. Additionally, with the characteristics of easy extraction and low immunogenicity, human umbilical cord-derived mesenchymal stem cells (UCMSCs) have been recognized as the preferred MSCs for transplantation [5].…”

Microenvironmental changes induced by placenta-derived mesenchymal stem cells restore ovarian function in ovariectomized rats via activation of the PI3K-FOXO3 pathway

“…showed that PD-MSCs have therapeutic bene ts in mice with premature ovarian failure because they regulate regulatory T-cell activity and cytokines [18,19].…”

Microenvironmental changes by placenta-derived mesenchymal stem cells restore the ovarian function in ovariectomized rat via activated PI3K-FOXO3 pathway

“…Because of these immunosuppressive properties, there are ongoing clinical trials with PD-MSCs in several disease types including certain autoimmune diseases [15][16][17]. Recently, Yin N et al, showed that PD-MSCs have therapeutic bene ts in mice induced with premature ovarian failure by regulating regulatory Tcell activity and cytokines [18,19].…”