Poly (ADP-ribose) polymerase inhibitor exposure reduces ovarian reserve followed by dysfunction in granulosa cells

The use of poly (ADP-ribose) polymerase (PARP) inhibitors is expected to increase, but their effect on fertility is still unclear. The aim of this study was to investigate the effect of PARP inhibitors on ovarian function. In an in vitro study, cultures of ovaries and granulosa cells (GCs) exposed to the PARP inhibitor olaparib were evaluated by real-time RT-PCR, histological study, and hormone assays. In an in vivo study, mice were administered olaparib orally and evaluated via in vitro fertilization (IVF), follicle count, immunohistochemical staining, and real-time RT-PCR. In vitro, the gene expression of GC markers decreased in the olaparib-treated group. Olaparib also negatively affected estradiol production and the expression of GC markers in cultured GCs, with abnormal morphology of GCs observed in the treated group. The follicle number indicated depletion of follicles due to atretic changes in the treatment group, both in vitro and in vivo. Also, olaparib reduced the number of retrieved oocytes and the fertilization rate of IVF, but they recovered after 3 weeks of cessation. Our results indicate that olaparib is toxic to ovaries.