Immunohistochemical and electron microscopic investigation of the effects of mesenchymal stem cells on the ovary in rats with ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome (OHSS) is a serious iatrogenic complication that develops as a result of gonadotropin administrations for ovulation induction during assisted reproductive treatments. Exogenous gonadotropin administrations cause an increase in vascular permeability by increasing the levels of vasoactive and inflammatory cytokines secreted from the ovaries. Fluid shift to the third space via increased vascular permeability, so life-threatening conditions such as edema, ascites, hypovolemia, and acute respiratory distress syndrome can be observed. Mesenchymal stem cells (MSCs) are multipotent cells whose anti-inflammatory, immunomodulatory, antioxidant, and antiapoptotic effects have been shown in many studies. In this study; the therapeutic effects of human umbilical cord-derived MSCs in an experimental OHSS rat model were investigated. For this purpose, MSCs whose DNA was labeled with Hoechst 3342 dye were injected intraperitoneally into the rats. After sacrification, histopathological evaluation of ovarian tissues was performed under light and electron microscope. Estradiol (E2) and IL-6 levels in serum samples were analyzed. In the OHSS group; hemorrhagic areas, vascular dilatations and edema were evident. While a decrease was observed compared to the control group in all follicle types developed in the cortex, a significant increase was observed in atretic follicles and corpus luteum structures. Serum E2, IL-6 levels and VEGF immunoreactivity were significantly higher in the OHSS group. A decrease was observed in edema, hemorrhagic areas and vascular dilatations in the OHSS group with the administration of MSCs. While it was observed that MSCs had a slight curative effect on follicle and corpus luteum numbers, although not statistically significant, it was found to have a therapeutic effect by causing a significant decrease in serum estradiol, IL-6 levels, and VEGF immunoreactivity. Ultrastructural changes were evaluated by electron microscopic analysis. These results show that MSCs have positive effects on the pathogenesis of OHSS. However, further experimental and clinical studies are needed to use MSCs as an alternative pharmacological agent in the treatment of OHSS. Key Words: OHSS, Mesenchymal Stem Cell, Human Umbilical Cord, VEGF, IL-6