Assessment of gonadal toxicity of PARP inhibitors on human ovary and testis

Objective: This research aimed to investigate the molecular together with cellular impacts of PARP inhibitors (Niraparib and Olaparib) on human reproductive cells and tissues. Methods: Human testicular and ovarian tissues, human luteinized granulosa cells as well as the COV434, and HGrC1 were used. xCELLigence, MTT, SRB, and Calcein/PI staining were used to check cell proliferation and viability. Western blotting, flow cytometry, and immunofluorescence techniques were utilized to look at apoptosis and cell death. PCR and Western blotting methods have been conducted to assess steroidogenic genes and proteins. Estradiol, progesterone, AMH, and testosterone levels were measured from the culture medium. Results: Inhibiting PARP results in a time and dose dependent reduction in the proliferation of cells induced apoptosis. In granulosa cells, the expression of genes involved in steroidogenesis was downregulated, resulting in a substantial reduction in progesterone synthesis, whereas estrogen and AMH levels remained unchanged. Olaparib dramatically elevated apoptotic markers in testicular tissue without affecting testosterone secretion. Conclusion: This study shows that PARP inhibitors significantly affect the cytotoxicity and steroidogenesis in human reproductive cells and tissues. Results underscore the need to evaluate possible reproductive concerns associated with PARP inhibitors, especially regarding fertility preservation. Keywords: PARP inhibitors, Niraparib, Olaparib, steroidogenesis, apoptosis, fertility