The Potential of Mouse Amniotic Fluid Stem Cells to Rescue Fertility of Ovarian Failure Mice
Date Issued
2012
Date
2012
Author(s)
Xiao, Guan-Yu
Abstract
The dogma of reproductive biology field is that female mammalian loss of germ cell renewal ability before birth, then the reserve of germ cells decreased during postnatal life until exhaustion, resulting in menopause and irreversible ovarian failure. Previous studies demonstrated that bone marrow-derived cells can rescue the fertility of mouse treated with drugs, busulfan and cyclophosphamide, which damage the germ cells in cancer patients. However, there was no evidence shown the restoring pathway of bone marrow-derived cells whether via germ cell differentiation, ovarian cell differentiation or paracrine factors secretion. Recently, it was reported that amniotic fluid stem cells (AFSCs) have low immunogenicity to avoid immunorejection and may have better differentiation ability than mesenchymal stem cells (MSCs). Therefore, we intend to investigate if AFSCs can recover female fertility via germline differentiation.
In this study, we established mouse AFSCs (mAFSCs) which expressing foreign enhanced green fluorescence protein (EGFP) that derived from EGFP bearing mouse conceptus (11.5 days). These mAFSCs exhibited the characteristics similar to bone marrow MSCs, and have the higher proliferation ability. In addition, mAFSCs express the pluripotent specific marker-Oct 4, and could differentiate into adipocyte, osteocyte and chondrocyte under appropriate condition. When mAFSCs were induced to differentiate into female germ cell, a subpopulation of these cells detached to each other gradually and formed aggregates resembling female germ cell formation. These cells subsequently expressed the germ cell marker-DAZL under induction condition. On further differentiation, these cells which formed the follicle-like structure that secreted estradiol under gonadotropin stimulation. Twenty-five days after differentiation induction, a few cells showed oocyte-like morphology and expressed the germ cell specific marker-VASA as well. To evaluate whether mAFSCs can recover female fertility, we use the ovarian failure model mice as recipients, and then transplanted EGFP bearing mAFSCs (EGFP-mAFSCs) into ovary of recipient mice. Four weeks after cell transplantation, numbers of developing follicle within host ovaries were significant higher than ovarian failure model mice, and numbers of atretic follicle were significant decreased. In addition, the fertility of all recipients was restored, but there was no fetus derived from EGFP-mAFSCs. Although EGFP-mAFSCs was observed within ovary after one month of transplantation, there was no evidence shown that mAFSCs differentiated into germ cell.
Collectively, this study demonstrated that mAFSCs have the potential to differentiate into germline in vitro. In addition, in vivo trial verified that mAFSCs can rescue the fertility in ovarian failure mice may via paracrine factors secretion. These findings implicated that the potentiality of clinical cell-transplantation therapy for the treatment of infertility.
Subjects
Amniotic fluid stem cells
Regenerative medicine
Ovarian failure
SDGs
Type
thesis
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