Use of Mesenchymal Stem Cells in Experimental Ovarian Damage

Abstract: Background: Bisphenol-A (BPA) has a well-proven deleterious effect on the hypothalamicpituitary-
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.