The study was conducted to evaluate the therapeutic potential of mesenchymal stem cells (MSCs) in Bisphenol A (BPA) -induced ovarian damage. The study was conducted on 50 mature female rats divided into: Group 1; control group, Group IIa, IIb: BPA group received oral gavage of BPA with two doses of 25, 50 mg/Kg body weight daily for 15 days, Group IIIa, IIIb; MSCs group intravenously injected with a single dose of MSCs (106 cells) after the last dose of BPA. Blood and ovarian tissue levels of Malondialdehyde (MDA) and gonadal axis hormones were assessed. Apoptosis was evaluated by TUNNEL assay and by apoptosis markers (FAS, FASL, Caspase 3, SLTM). Histological examination of ovarian tissue was assessed. Histological examination of ovarian tissues revealed that at high dose of BPA, there was significant increase in the number of atretic follicles whereas the numbers of primordial, primary, secondar, graafian follicles were significantly decreased. Moreover, all genetic and protein markers of apoptosis were significantly elevated in BPA treated rat groups with decreased estrogen receptor expression in the ovarian tissue. Results also showed significant elevation in plasma levels of LH and FSH, ovarian tissue levels of MDA, significant decrease in estradiol (E2), progesterone. Increased apoptotic cells were confirmed by TUNEL assay. All histological and laboratory abnormalities were significantly ameliorated after treatment with MSCs. In conclusion, follicles atresia is caused by BPA through upregulated expression of apoptosis related genes. MSCs induced significant amelioration of BPA induced-ovarian damage as regards apoptosis markers, biochemical and gonadal axis hormones.
Background:
Bisphenol-A (BPA) has a well-proven deleterious effect on the hypothalamic-pituitary-gonadal axis.
Objectives:
The current study investigated the therapeutic potentials of mesenchymal stem cells (MSCs) in a murine model of BPA-induced ovarian damage.
Methods:
Fifty adult female rats were divided into: Group 1; control group, Group IIa, IIb: rats were given oral gavage of BPA (25 and 50 mg/Kg body weight respectively) on a daily basis for 15 days, and Group IIIa, IIIb; rats were intravenously treated with of MSCs (106 cells) after receiving the last dose of BPA as in group II. Plasma and ovarian tissue levels of Malondialdehyde (MDA) and gonadal axis hormones were assessed. Apoptosis was evaluated by TUNNEL assay and by apoptosis markers (FAS, FASL, Caspase 3, SLTM). A histological examination of ovarian tissue was also conducted.
Results:
BPA resulted in a significant elevation in plasma levels of LH, FSH, and ovarian tissue levels of MDA and a significant decrease in estradiol and progesterone. All genetic and protein markers of apoptosis were elevated in BPA treated group with decreased oestrogen receptor expression in the ovarian tissue. Increased apoptotic cells were confirmed by TUNEL assay. A high dose of BPA was able to increase the number of atretic follicles in the ovarian tissue whereas the numbers of primordial, primary, secondary and Graafian follicles were decreased. All the laboratory and histological abnormalities were ameliorated by treatment with MSCs.
Conclusion:
The antioxidant and anti-apoptotic effects of MSCs could possibly explain the ability of this therapeutic modality to ameliorate BPA-induced-ovarian damage.
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