Ovarian toxicity of paclitaxel and effect on fertility in the rat.
OBJECTIVE
Taxanes are regarded as key chemotherapy agents for breast cancer and gynecologic malignancies; therefore the ovarian toxicity of paclitaxel (PTX) is a matter of importance to younger women with malignancies. We examined the ovarian toxicity of PTX and its influence on fertility in rats.


METHODS
Female Wistar rats aged 6-8 weeks received five doses of PTX at 3-day intervals. Ovarian toxicity was assessed by counting follicles, corpora lutea and atretic follicles, as well as by detecting apoptosis and measuring serum levels of estradiol (E2) and progesterone (P4). Fertility was assessed by mating females immediately or 24 days after PTX treatment. The number of fetuses, implantations and resorption sites was counted in each group.


RESULTS
Exposure to PTX caused a decrease of antral follicles, but not primordial or pre-antral follicles. The number of corpora lutea showed a significant decrease, while follicular atresia was increased significantly. Apoptosis was only detected in antral follicles. Serum E2 levels were lower than in control rats, but not significantly, while P4 levels did not differ from those in control rats. Rats mated immediately after PTX treatment showed a significant decrease of fetuses and implantations, but these effects were not detected in rats mated at 24 days after treatment.


CONCLUSIONS
Our findings suggest that the ovarian toxicity of PTX is mild and transient. Use of PTX may help to maintain the fertility of younger women because the fertility of rats was not influenced at 24 days after exposure to this drug.
Tarumi
Wataru
W
Department of Bioresource Sciences, Nihon University, Japan.
Suzuki
Nao
N
Takahashi
Noriyuki
N
Kobayashi
Yoichi
Y
Kiguchi
Kazushige
K
Sato
Kahei
K
Ishizuka
Bunpei
B
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D003338:Corpus Luteum / Q000187:drug effects; D004958:Estradiol / Q000097:blood; D005260:Female; D005298:Fertility / Q000187:drug effects*; D006080:Ovarian Follicle / Q000187:drug effects; D010053:Ovary / Q000187:drug effects*; D017239:Paclitaxel / Q000633:toxicity*; D011247:Pregnancy; D011374:Progesterone / Q000097:blood; D051381:Rats; D017208:Rats, Wistar
D000972:Antineoplastic Agents, Phytogenic; D011374:Progesterone; D004958:Estradiol; D017239:Paclitaxel