Abstract
BackgroundTo explore the mechanism of human umbilical cord-derived mesenchymal stem cell (hUMSC) transplantation to improve ovarian function and the endometrial receptivity in autoimmune premature ovarian failure (POF) mice.MethodsThe POF model was established in mice treated with zona pellucida 3 polypeptide fragment (zona pellucida 3, ZP3). The hUMSCs were transplanted into the POF mice through tail vein injection. Following the transplantation, the serum hormone levels of follicle stimulating hormone (FSH), estrogen (E2), progesterone (P), γ-interferon (IFN-γ), interleukin-2 (IL-2), and interleukin-4 (IL-4) were evaluated by ELISA analysis. Morphological changes of ovarian and uterus tissues were examined by HE staining and immunohistochemistry. The expression of Th1/Th2 cytokines of T cells in spleen and CD56+CD16− cells (uterine natural killer cells, uNK cells) in uterine was measured by flow cytometry (FCM) and immunohistochemistry. The expression of HOXA10 in uterine endometrium was examined by immunohistochemistry and RT-PCR analysis. The pinopodes of epithelial cells in uterine endometrium were examined by scanning electron microscopy.ResultsFollowing hUMSC transplantation, the serum levels of E2, P, and IL-4 were increased but FSH, IFN-γ, and IL-2 levels were decreased in POF mice. Also, the transplantation of hUMSCs caused an increase in total number of healthy follicles and decrease of atresia follicles. The expression of HOXA10 gene was significantly increased but the CD56+CD16− uNK cells decreased in the endometrium of uterine. The ratio of Th1/Th2 cytokines was also significantly decreased.ConclusionThe data suggest that the recovery of ovarian function and endometrial receptivity in POF mice was regulated by the balance of Th1/Th2 cytokines and expression of uNK cells in the endometrium following hUMSC transplantation.
Highlights
To explore the mechanism of human umbilical cord-derived mesenchymal stem cell transplantation to improve ovarian function and the endometrial receptivity in autoimmune premature ovarian failure (POF) mice
The data suggest that the recovery of ovarian function and endometrial receptivity in POF mice was regulated by the balance of Th1/Th2 cytokines and expression of Uterine natural killer (uNK) cells in the endometrium following Human umbilical cord-derived mesenchymal stem cells (hUMSCs) transplantation
The differentiation capacity of hUMSCs towards the chondrogenic was demonstrated by alizarin red staining
Summary
To explore the mechanism of human umbilical cord-derived mesenchymal stem cell (hUMSC) transplantation to improve ovarian function and the endometrial receptivity in autoimmune premature ovarian failure (POF) mice. Stem cell therapy has gained great interest as a promising approach to treat POF. Some papers and our previous studies have shown that mesenchymal stem cell transplantation can significantly restore the ovarian function and follicle development in autoimmune-induced POF mice. The exact mechanism on how mesenchymal stem cell transplantation restores the ovarian function is still unclear. The follicular development, endometrial receptivity and maternal-fetal interaction are three key factors for successful pregnancy. The investigation on the mechanism of hUMSC transplantation to treat POF mice has focused on how it recovers ovarian function and affects the endometrial receptivity in uterine
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