Intraovarian Transplantation of Female Germline Stem Cells Rescue Ovarian Function in Chemotherapy-Injured Ovaries

• Published in: PloS one 2015-10, Vol.10 (10), p.e0139824-e0139824
• Main Authors: Xiong, Jiaqiang, Lu, Zhiyong, Wu, Meng, Zhang, Jinjin, Cheng, Jing, Luo, Aiyue, Shen, Wei, Fang, Li, Zhou, Su, Wang, Shixuan
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Antineoplastic Combined Chemotherapy Protocols - toxicity; Busulfan - administration & dosage; Cancer; Cancer patients; Care and treatment; Chemotherapy; Cryopreservation; Cyclophosphamide - administration & dosage; Diagnosis; Eggs; Female; Females; Fertility; Gene Expression; Graft rejection; Health aspects; Hormone replacement therapy; Hormones - blood; Infertility; Karyotyping; Menopause; Mice; Mice, Inbred C57BL; Offspring; Oocytes; Ovarian cancer; Ovaries; Ovary - cytology; Ovary - drug effects; Ovary - physiopathology; Patients; Pregnancy; Recovery of function; Rejection; Reproductive status; Risk factors; Rodents; Stem Cell Transplantation; Stem cells; Transplantation; Viruses; Women's health
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0139824

Early menopause and infertility often occur in female cancer patients after chemotherapy (CTx). For these patients, oocyte/embryo cryopreservation or ovarian tissue cryopreservation is the current modality for fertility preservation. However, the above methods are limited in the long-term protection of ovarian function, especially for fertility preservation (very few females with cancer have achieved pregnancy with cryopreserved ovarian tissue or eggs until now). In addition, the above methods are subject to their scope (females with no husband or prepubertal females with no mature oocytes). Thus, many females who suffer from cancers would not adopt the above methods pre- and post-CTx due to their uncertainty, safety and cost-effectiveness. Therefore, millions of women have achieved long-term survival after thorough CTx treatment and have desired to rescue their ovarian function and fertility with economic, durable and reliable methods. Recently, some studies showed that mice with infertility caused by CTx can produce normal offspring through intraovarian injection of exogenous female germline stem cells (FGSCs). Though exogenous FGSC can be derived from mice without immune rejection in the same strain, it is difficult to obtain human female germline stem cells (hFGSCs), and immune rejection could occur between different individuals. In this study, infertility in mice was caused by CTx, and the ability of FGSCs to restore ovarian function or even produce offspring was assessed. We had successfully isolated and purified the FGSCs from adult female mice two weeks after CTx. After infection with GFP-carrying virus, the FGSCs were transplanted into ovaries of mice with infertility caused by CTx. Finally, ovarian function was restored and the recipients produced offspring long-term. These findings showed that mice with CTx possessed FGSCs, restoring ovarian function and avoiding immune rejection from exogenous germline stem cells.