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HucMSC-Derived Exosomes Mitigate the Age-Related Retardation of Fertility in Female Mice.

Molecular therapy : the journal of the American Society of Gene Therapy (2020-02-26)
Weijie Yang, Jing Zhang, Boqun Xu, Yuanlin He, Wei Liu, Jiazhao Li, Songying Zhang, Xiaona Lin, Dongming Su, Tinghe Wu, Jing Li
ABSTRACT

In mammals, resting primordial follicles serve as the ovarian reserve. The decline in ovarian function with aging is characterized by a gradual decrease in both the quantity and quality of the oocytes residing within the primordial follicles. Many reports show that mesenchymal stem cells have the ability to recover ovarian function in premature ovarian insufficiency (POI) or natural aging animal models; however, the underlying mechanism remains unclear. In this study, using exosomes derived from human umbilical cord mesenchymal stem cells (HucMSC-exos), we found the specific accumulation of exosomes in primordial oocytes. The stimulating effects of exosomes on primordial follicles were manifested as the activation of the oocyte phosphatidylinositol 3-kinase (PI3K)/mTOR signaling pathway and the acceleration of follicular development after kidney capsule transplantation. Further analysis revealed the stimulatory effects of HucMSC-exos on primordial follicles were through carrying functional microRNAs, such as miR-146a-5p or miR-21-5p. In aged female mice, the intrabursal injection of HucMSC-exos demonstrated the recovery of decreased fertility with increased oocyte production and improved oocyte quality. Although assisted reproductive technologies have been widely used to treat infertility, their overall success rates remain low, especially for women in advanced maternal age. We propose HucMSC-exos as a new approach to mitigate the age-related retardation of fertility in women.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Triton X-100, laboratory grade
Sigma-Aldrich
Hyaluronidase from bovine testes, Type I-S, lyophilized powder, 400-1000 units/mg solid
Millipore
Millicell Cell Culture Insert, 12 mm, hydrophilic PTFE, 0.4 µm, Hydrophilic PTFE cell culture insert with pore size of 0.4 µm used in a 24-well plate for Cell Attachment, Cell Culture, Cell Differentiation, Fluorescence & Low Protein Binding.