The effect of L-carnitine on oocyte mitochondrial health and biomarkers on cyclophosphamide chemotherapy drug in mice

Abstract

Improving oocyte competence during chemotherapy is widely known as a contributing factor to increasing the probability of fertility. Additionally, the role of cumulus cells in oocyte quality is of utmost importance. Therefore, this study was designed to simultaneously probe into the relative gene expression of oocytes and cumulus cells as biomarkers of oocyte quality with cyclophosphamide and L-carnitine treatment. A total of 60 adult NMRI mice were divided into four groups: control, L-carnitine (LC), cyclophosphamide (CP), and cyclophosphamide+L-carnitine (CP+LC). The relative mRNA expression levels of oocyte quality genes including growth differentiation factor 9 (Gdf9), hyaluronan synthase 2 (Has2), and mitochondrial sirtuin 3 (Sirt3) in oocytes, and genes involved in bilateral communication between cumulus cells and between the oocyte and its neighboring cumulus cells including connexin 37 (Cx37) and connexin 43 (Cx43) were detected by Real-time-PCR. DCFH-DA staining analyzed the level of intracellular ROS in oocytes. Under the influence of L-carnitine, Gdf9, Has2, Cx43, and Cx37 were significantly up-regulated (p ≤ 0.05). However, cyclophosphamide considerably reduced the expression of all these genes (p ≤ 0.05). The expression of the Sirt3 gene in the CP group increased significantly compared to the other groups (p ≤ 0.05). Analysis of fluorescent images revealed that the level of intracellular ROS in the cyclophosphamide group was significantly increased compared to the other groups (p ≤ 0.05), while it plummeted in the L-carnitine group (p ≤ 0.05). L-carnitine as an antioxidant can reduce the destructive effects of cyclophosphamide and enhance bilateral communications between oocytes and cumulus cells, and it may ultimately lead to an increase in the fertility rate.