These findings met the criteria for MSCs identification by The Association of International Cell Therapy. intraperitoneal injection and intragastric administration, respectively. After either 7 or 14?days, ovarian function was evaluated by the oestrus cycle, hormone levels, ovarian index, fertility rate, and ovarian morphology. The karyotype was identified in offspring by the G-banding technique. hAMSCs tracking, immunohistochemical staining, and real-time polymerase chain reaction (PCR) were used to assess the molecular mechanisms of injury and repair. Results The oestrus cycle was recovered after hAMSCs transplantation at 7 and 14?days. Oestrogen levels increased, while follicle-stimulating hormone levels decreased. The ovarian index, fertility rate, and population of follicles at different stages were significantly increased. The newborn mice had no obvious deformity and showed normal growth and development. The normal offspring mice were also fertile. The tracking of hAMSCs revealed that they colonized in the ovarian stroma. Immunohistochemical and PCR analyses indicated that changes in proteins and genes might affect mature follicle formation. Conclusions These results suggested that hAMSCs transplantation can improve injured ovarian tissue ARS-1323 structure and function in oxidatively damaged POF mice. Furthermore, the mechanisms of hAMSCs are related to promoting follicular development, granulosa cell proliferation, and secretion function by improving the local microenvironment of the ovary. Keywords: Premature ovarian failure, Hydrogen peroxide, Human amniotic mesenchymal stem cells, Diethylstilbestrol, Reproduction, Ovary, Microenvironment Background Premature ovarian failure (POF) is a gynaecological endocrine disease characterized by abnormal oestrogen levels and gonadotropin, which manifests as irregular menstruation, amenorrhea, infertility, and perimenopause syndrome affecting women younger than 40?years of age. Approximately 1% of women under the age of 40?years could develop POF [1]. The reasons for POF may be varied, including genetic predisposition, autoimmune conditions, infections, and iatrogenic causes [2]. Long-term health consequences, including psychological distress, infertility, osteoporosis, heart disease, autoimmune disorders, and increased mortality, have significant impacts on the quality of life for women diagnosed with POF [3]. The mechanisms of POF genesis and progression involve follicle atresia, granulosa cell apoptosis, interstitial fibrosis, and disturbed sex hormone levels. There may also be an imbalance in immune function and inflammatory responses [4, 5]. Therefore, in addition to increased follicle-stimulating hormone (FSH) and decreased oestrogen and anti-Mllerian hormone(AMH) levels in the blood circulation, changes in the expression of a series of molecules also occur in the local ovary [6, 7], including a variety of follicular development-related growth factors, such as the forkhead box L2 gene (FOXL2), octamer combination transcription factors (Oct4), growth differentiation factor-9 (GDF-9), leukaemia inhibitory factor (LIF), and stem cell factor (SCF). Thus far, there are limitations of hormone replacement therapy, in vitro oocyte maturation or oocyte/ovarian cryopreservation for transplantation on POF [1, 3]. However, no radical cure is yet available for reversing the POF to a normal ovarian structure and function. There is an urgent need to improve the ARS-1323 ARS-1323 current treatment strategies. Stem cell therapy has been suggested as a promising measure in the treatment of several human diseases and ARS-1323 applications of regenerative medicine because of the self-renewal and differentiation abilities of these cells, which can replace the damaged tissue, or the paracrine cytokines and exosomes, which can rescue injured tissues [8, 9]. Recent studies have shown that bone marrow mesenchymal stem cells (MSCs) [10C14], amniotic fluid stem cells [15C18], adipose-derived stem cells [19, 20], human umbilical cord MSCs [21, 22], and menstrual blood stem cells [23C25] can restore ovarian function and fertility in mice models of POF. However, many of the suitable cell types currently identified for clinical application involve invasive procedures or have a low ARS-1323 magnitude of the original stem cells. Amnion is a waste product of perinatal tissue sources so the procedure to obtain human amniotic mesenchymal stem cells (hAMSCs) is noninvasive and not under ethical debate. hAMSCs may prevent age-related reductions in proliferative and differentiation potential characteristics [26]. hAMSCs have the common characteristics of multipotent MSCs, including self-renewal, high rates of proliferation, multi-differentiation capacity, immunosuppressive and anti-inflammatory effects, and paracrine activity [27C32]. Researchers have Arnt reported that hAMSCs secrete significant amounts.
These findings met the criteria for MSCs identification by The Association of International Cell Therapy