Adipose-Derived Mesenchymal Stem Cell Transplantation in Chemotherapy-Induced Premature Ovarian Insufficiency: the Role of Connexin and Pannexin

Abstract

In women undergoing chemotherapy, it is inevitable that infertility risk will increase because of impaired reproductive functions. Premature ovarian insufficiency (POI), which occurs as a devastating result of chemotherapy, is the complete depletion or dysfunction of ovarian follicles. Adipose-derived mesenchymal stem cells (ADMSCs) transplantation is among the alternative treatment methods for POI, which currently do not have an effective treatment method. Apoptosis of granulosa cells in POI is seen as the main mechanism of the disease. It is also reported that in addition to molecules directly associated with apoptosis, connexins, and pannexins are also potential effector molecules in apoptosis. The roles of these molecules in POI, which are known to play a role in many important mechanisms in the ovary, are unknown. In this study, it was aimed to analyze the expressions of Connexin43 and Pannexin1, which are thought to be effective in the formation of POI, and to show the relationship between the antiapoptotic effects of ADMSCs transplantation and these molecules in POI. For this purpose, Caspase3, Connexin43, Pannexin1 proteins, and mRNA expressions were analyzed by immunohistochemistry and RT-qPCR, and AMH levels were measured by ELISA. It was determined that Pannexin1, Caspase3 proteins, and mRNA levels increased in the POI, while Pannexin1 and Caspase3 expressions decreased in the ADMSCs treated group. While Connexin43 level decreased in POI, Connexin43 protein and mRNA levels increased in ADMSCs group. Consequently, this study demonstrated for the first time that Connexin43 and Pannexin1 were associated with apoptosis in POI. In addition, it was revealed that ADMSCs transplantation could produce antiapoptotic effects by modulating these molecules.