Human umbilical cord mesenchymal stem cells improve the reserve function of perimenopausal ovary via a paracrine mechanism

Stem Cell Res Ther. 2017 Mar 9;8(1):55. doi: 10.1186/s13287-017-0514-5.

Abstract

Background: Human umbilical cord mesenchymal stem cells (hUCMSCs) are a type of pluripotent stem cell which are isolated from the umbilical cord of newborns. hUCMSCs have great therapeutic potential. We designed this experimental study in order to investigate whether the transplantation of hUCMSCs can improve the ovarian reserve function of perimenopausal rats and delay ovarian senescence.

Method: We selected naturally aging rats confirmed by vaginal smears as models of perimenopausal rats, divided into the control group and the treatment group, and selected young fertile female rats as normal controls. hUCMSCs were transplanted into rats of the treatment group through tail veins. Enzyme-linked immunosorbent assay (ELISA) detected serum levels of sex hormones, H&E staining showed ovarian tissue structure and allowed follicle counting, immunohistochemistry and western blot analysis revealed ovarian expression of hepatocyte growth factor (HGF), vascular endothelial cell growth factor (VEGF), and insulin-like growth factor-1 (IGF-1), polymerase chain reaction (PCR) and western blot analysis revealed hUCMSCs expression of HGF, VEGF, and IGF-1.

Results: At time points of 14, 21, and 28 days after hUCMSCs transplantation, estradiol (E2) and anti-Müllerian hormone (AMH) increased while follicle-stimulating hormone (FSH) decreased; ovarian structure improved and follicle number increased; ovarian expression of HGF, VEGF, and IGF-1 protein elevated significantly. Meanwhile, PCR and western blot analysis indicated hUCMSCs have the capacity of secreting HGF, VEGF, and IGF-1 cytokines.

Conclusions: Our results suggest that hUCMSCs can promote ovarian expression of HGF, VEGF, and IGF-1 through secreting those cytokines, resulting in improving ovarian reserve function and withstanding ovarian senescence.

Keywords: HGF; IGF-1; Ovarian reserve function; Paracrine; Perimenopausal; VEGF; hUCMSCs.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Proliferation / genetics
  • Cellular Senescence / genetics
  • Coculture Techniques
  • Female
  • Follicle Stimulating Hormone / genetics*
  • Gene Expression Regulation, Developmental
  • Hepatocyte Growth Factor / genetics*
  • Humans
  • Insulin-Like Growth Factor I / genetics*
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology
  • Ovarian Follicle / growth & development*
  • Ovarian Follicle / metabolism
  • Ovarian Reserve / genetics
  • Paracrine Communication / genetics
  • Perimenopause
  • Rats
  • Umbilical Cord / cytology
  • Vascular Endothelial Growth Factor A / genetics*

Substances

  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat
  • Hepatocyte Growth Factor
  • Insulin-Like Growth Factor I
  • Follicle Stimulating Hormone