Effects of paclitaxel and cisplatin on in vitro ovarian follicle development

Despite its importance in pre-chemotherapy counselling, specific reproductive toxicological information about cisplatin and paclitaxel is very rare. This study aimed to investigate the concentrations at which cisplatin and paclitaxel, alone or combined, affect the in vitro development of ovarian follicles. Their differential effects on the oocytes and surrounding granulosa cells was also evaluated.

Ovarian follicles were cultured in vitro using gonadotropins and treated with 10^-8-10^-10 M of cisplatin, paclitaxel, or both. At day 13, granulosa cells and oocytes were retrieved and used for imaging and functional analyses.

Follicular survival and growth was significantly suppressed in all treatment groups at 10^-9 M or higher concentrations, and additive effects were observed in the combination group (p < 0.01). Oocyte-specific genes such as growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) were more suppressed in the paclitaxel group than in the cisplatin group. Granulosa cell-specific gene suppression and its electron microscopic alteration were more prominent in the cisplatin group than in the paclitaxel group. X-linked inhibitor of apoptosis protein (XIAP) expression of granulosa cells was also further down-regulated in the cisplatin group.

These data provide an insight into the critical concentrations regarding in vitro follicular development and the differential effects of chemotherapeutic effects on oocytes and granulosa cells. Further studies are necessary to develop more efficient pre-chemotherapeutic fertility-sparing medical treatment that can evade oocyte-specific damage.