The therapeutic effect of abaloparatide on the cyclophosphamide induced rat azoospermia model

Drug-related infertility is one of the biggest health problems. Cyclophosphamide, which is widely used for cancer treatments, is known to cause infertility by damaging germ cells. This study aimed to investigate the protective effect of abaloparatide, a parathyroid hormone receptor analog, on testicular damage induced by cyclophosphamide treatment. In this study, 30 male Wistar rats, 12-16 weeks old, were randomly divided into 5 groups: control, sham, abaloparatide, cyclophosphamide, and abaloparatide+cyclophosphamide. Testicular damage was induced by administering 15 mg/kg of cyclophosphamide intraperitoneally once a day for 20 days. Abaloparatide was administered intraperitoneally at 10 µg/kg once a day for 56 days. At the end of the applications, the testicular tissues of the sacrificed animals were divided into two for examination using histology and Western blot techniques. Histological examinations were performed with H&E staining, and morphological and Johnsen scores were evaluated. Preparations made using immunohistochemical techniques and primary CREB, PCNA, HSPA4, and REC8 antibodies were evaluated with the ImageJ program. Molecular examinations were performed with the Western blot method using the same primary antibodies. It was observed that cyclophosphamide disrupted testicular morphology and decreased testicular weight and Johnsen scores. In the cyclophosphamide group, CREB, PCNA, HSPA4, and REC8 immunoreactivity and protein levels were found to be significantly reduced compared to the control, sham, ABL, and ABL+SF groups (p<0.05). It was determined that abaloparatide preserved testicular morphology and weight, increased Johnsen scores, and reduced weight loss in the groups it was administered to, and also increased the expression of CREB, PCNA, HSPA4, and REC8. This study concluded that abaloparatide protected against germ cell loss caused by cyclophosphamide, improved meiosis (REC8) and sperm quality (HSPA4), and achieved its effect through the CREB/PCNA pathway. Keywords: Abaloparatide, CREB, GAPDH, HSPA4, Infertility, PCNA, REC8, Cyclophosphamide