Human Amniotic Fluid Mesenchymal Stem Cells Improve Ovarian Function During Physiological Aging by Resisting DNA Damage

Abstract

Many studies have shown that mesenchymal stem cells have the ability to restore function in models of premature ovarian insufficiency disease, but few studies have used stem cells in the treatment of ovarian physiologic aging (OPA). This experimental study was designed to determine whether human amniotic fluid mesenchymal stem cells (hAFMSCs) have the ability to recover ovarian vitality and to determine how they function in this process. Mice (12-14 months old) were used in this study, and young fertile female mice (3-5 months old) were the control group. Ovarian markers for four stages of folliculogenesis and DNA damage genes were tested by qPCR and western blot. hAFMSCs were used to treat an OPA mouse model, and the animals treated with hAFMSCs displayed better therapeutic activity in terms of the function of the mouse ovary, increasing follicle numbers and improving hormone levels. In addition, our results demonstrated that the marker expression level in ovarian granular cells from patients with OPA was elevated significantly after hAFMSC treatment. In addition, the proliferation activity was improved, and apoptosis was dramatically inhibited after hAFMSCs were cocultured with hGCs from OPA patients. Finally, in this study, hAFMSCs were shown to increase the mRNA and protein expression levels of ovarian markers at four stages of folliculogenesis and to inhibit the expression of DNA damage genes. These works have provided insight into the view that hAFMSCs play an integral role in resisting OPA. Moreover, our present study demonstrates that hAMSCs recover ovarian function in OPA by restoring the expression of DNA damage genes.

Insights on the Human Amniotic Membrane in Clinical Practice with a Focus on the New Applications in Retinal Surgery

“…3). Regarding the anatomical and functional outcomes between dehydrated and cryopreserved hAM, a group of authors reported no significant differences in 17 consecutive cases of recurrent macular holes [94]. It may be interesting in the future to investigate micronized hAMs for retinal surgical cases.…”

Application of Perinatal Derivatives in Ovarian Diseases

“…In the normal developmental period of the ovarian follicular cycle, all phases of follicular atresia are closely related to the activity levels of granulosa cells. In both aging and clinical context, increased apoptosis and decreased proliferation of granulosa cells is the principal mechanism driving follicular atresia and arrest ( Ding et al, 2018 ; Huang et al, 2020 ). Current knowledge on ovarian dysfunction in the human, murine and bovine reproductive system will be briefly introduced.…”

“…In situations related to the life of an individual, such as age-related diseases, natural aging, aging induced by therapeutic interventions and diseases, granulosa cells can be prone to persistent senescence ( Huang et al, 2020 ). Physiological ovarian aging is a gradual decrease in both the quantity and quality of oocytes residing within the primordial follicles ( Yang et al, 2020 ) and is linked to ovarian aging characterized by apoptosis of oocytes, follicular atresia, cessation of menstruation and elevated plasma levels of FSH ( Ding et al, 2020a ; Huang et al, 2020 ). The condition affects 1% of women worldwide by the age of 40 years ( Ding et al, 2020a ; Huang et al, 2020 ).…”

Bone marrow mesenchymal stem cells derived from juvenile macaques reversed ovarian ageing in elderly macaques

“…Many clinical and basic studies have shown the effectiveness of mesenchymal stem cells (MSCs) in the treatment of ovarian ageing, and MSCs have been demonstrated to be more effective than other cell types in improving ovarian function [ 9 ]. Human amniotic fluid MSCs (hAFMSCs) can restore ovarian physiological ageing (OPA) function [ 10 ]. Human placental MSCs (hPMSCs) can inhibit oxidative stress and apoptosis, thereby improving ovarian function [ 11 ].…”