Nanoparticle Delivery Systems Reduce the Reproductive Toxicity of Docetaxel in Rodents

Various docetaxel (DTX)-loaded nanoparticle delivery systems have been designed to enhance the solubility and pharmacological effects of DTX. However, the toxicity changes of these nano-modified DTX (nano-DTX) are not yet clear enough. Herein, to compare the reproductive toxicity between conventional DTX and nano-DTX, we performed sperm toxicity test in mice, and fertility and early embryo-fetal developmental toxicity test in rats. It was found that DTX severely repressed spermatogenesis and sperm motility, and dramatically increased sperm abnormality in mice and rats. Moreover, DTX significantly decreased copulation, conception and fertility indexes in rats, and no positive pregnant female rat was obtained after treatment with DTX. However, nano-DTX significantly reduced DTX-induced toxicity to sperm. Most importantly, nano-DTX obviously converted DTX-induced fertility and early embryo-fetal developmental toxicity. Furthermore, organ weights and histopathology examination revealed DTX, but not nano-DTX, significantly decreased testis and epididymis weights, and induced obvious histopathological atrophy of testes and epididymides in rats. Further studies indicated that changed activity of lactate dehydrogenase C4 (LDH-C4) in rodents testes was mainly responsible for the above observations. These results strongly support the idea that DTX-loaded nanoformulations have the potential to overcome the reproductive toxicity of DTX.