Transient impact of paclitaxel on mouse fertility and protective effect of gonadotropin-releasing hormone agonist

Paclitaxel (PXL) is a chemotherapeutic agent widely used in solid tumors. However, whether PXL causes premature ovarian insufficiency in women of reproductive age remains controversial. The aim of the present study was to answer how and for how long PXL affects fertility, and to identify the protective effect of gonadotropin-releasing hormone agonist (GnRHa) in mice. A single dose of PXL was administered to 7-week-old female ICR mice. Mice were treated with GnRHa for 1 estrous cycle prior to chemotherapy, and for another following chemotherapy. On the days 1, 6, 11 and 16 following the administration of PXL, mice were assessed by ovarian histology, ovarian stimulation and mating experiment. Multiple doses of PXL were also administered to verify the duration of the gonadotoxicity of PXL. It was determined that PXL only destroyed antral follicles on day 1 following chemotherapy without reducing primordial follicles. In vitro experiments revealed that PXL impaired oocytes in metaphase, excluding those at the germinal vesicle stage. The number and quality of retrieved metaphaseII(MII) oocytes in PXL-exposed mice were reduced on day 1 following chemotherapy, which was recovered on day 11. MII oocytes from mice pretreated with GnRHa recovered on day 6 following chemotherapy. Following 3 estrous cycles in mice after the last dose of the 3-dose paclitaxel administration, follicles in all stages and retrieved MII oocytes were recovered. It was concluded that the impairment caused by PXL on follicles and oocytes in mice lasted for <3 estrous cycles, which was shortened by pretreatment of GnRHa.